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  • 1.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Mobäck, Caroline
    Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Jakobsson, Sandra
    Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Germany.
    Hoffmann, Johannes J. M. L.
    Abbott GmbH and Co KG, Germany.
    Iron depletion in blood donors - Have extended erythrocyte and reticulocyte parameters diagnostic utility?2015In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 53, no 1, p. 76-81Article in journal (Refereed)
    Abstract [en]

    Background: Blood donation is associated with iron depletion, but donor iron status is not usually investigated, as such tests are cumbersome and costly. It would therefore be desirable to have simple, fast and inexpensive tests that give information on a donors risk of developing iron depletion. In a pilot study we investigated whether novel erythrocyte and reticulocyte parameters can serve this goal. Methods: In regular blood donors extended red cell parameters were measured using the Abbott CELL-DYN Sapphire hematology analyzer and conventional biochemical tests of iron status. Donors were compared with a regionally matched group of non-donating controls. Results: In the controls, the reference ranges of extended RBC parameters were well comparable to published data. Donors had significantly more microcytic RBC than controls (median 0.9 vs 0.6%), lower serum ferritin concentration (median 43 vs 91 mg/L) and higher soluble transferrin receptor/ferritin index (median 1.60 vs 1.27). Overall 18-28% of the donors were iron depleted. Moreover, 3.3% of donors had iron-restricted erythropoiesis. Microcytic RBC and reticulocyte mean cell hemoglobin content predicted iron depletion with 70% and 64% sensitivities and specificities of 72% and 78%, respectively. When combined these two parameters increased the sensitivity to 82%. Conclusions: Our results in Swedish blood donors confirm a high prevalence of iron depletion, despite iron supplementation used by about half of the donors. Microcytic RBC and MCHr appeared to be helpful in identifying iron-depleted donors, who might benefit from iron supplementation. We recommend larger prospective investigations in order to confirm and extend the findings of this pilot study. (C) 2015 Elsevier Ltd. All rights reserved.

  • 2.
    Abalo, Kossi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine. Karolinska Inst, Dept Med Solna, Clin Epidemiol Div, Stockholm, Sweden..
    Smedby, Karin E.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Div, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden..
    Ekberg, Sara
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Div, Stockholm, Sweden..
    Eloranta, Sandra
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Div, Stockholm, Sweden..
    Pahnke, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine.
    Albertsson-Lindblad, Alexandra
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Div Oncol, Lund, Sweden..
    Jerkeman, Mats
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Div Oncol, Lund, Sweden..
    Glimelius, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine. Karolinska Inst, Dept Med Solna, Clin Epidemiol Div, Stockholm, Sweden..
    Secondary malignancies among mantle cell lymphoma patients2023In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 195, article id 113403Article in journal (Refereed)
    Abstract [en]

    Purpose:

    With modern treatments, mantle cell lymphoma (MCL) patients more frequently experience long-lasting remission resulting in a growing population of long-term survivors. Follow-up care includes identification and management of treatment-related late-effects, such as secondary malignancies (SM). We conducted a populationbased study to describe the burden of SM in MCL patients.

    Methods:

    All patients with a primary diagnosis of MCL, aged >= 18 years and diagnosed between 2000 and 2017 in Sweden were included along with up to 10 individually matched population comparators. Follow-up was from twelve months after diagnosis/matching until death, emigration, or December 2019, whichever occurred first. Rates of SM among patients and comparators were estimated using the Anderson-Gill method (accounting for repeated events) and presented as hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age at diagnosis, calendar year, sex, and the number of previous events.

    Results:

    Overall, 1 452 patients and 13 992 comparators were followed for 6.6 years on average. Among patients, 230 (16%) developed at least one SM, and 264 SM were observed. Relative to comparators, patients had a higher rate of SM, HRadj= 1.6 (95%CI:1.4-1.8), and higher rates were observed across all primary treatment groups: the Nordic-MCL2 protocol, R-CHOP, R-bendamustine, ibrutinib, lenalidomide, and R-CHOP/Cytarabine. Compared to Nordic-MCL2, treatment with R-bendamustine was independently associated with an increased risk of SM, HRadj= 2.0 (95%CI:1.3-3.2). Risk groups among patients were those with a higher age at diagnosis (p < 0.001), males (p = 0.006), and having a family history of lymphoma (p = 0.009). Patients had preferably higher risk of melanoma, other neoplasms of the skin and other hematopoietic and lymphoid malignancies.

    Conclusions:

    MCL survivors have an increased risk of SM, particularly if treated with R-bendamustine. The intensive treatments needed for long-term remissions are a concern, and transition to treatment protocols with sustained efficacy but with a lower risk of SM is needed.

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  • 3.
    Abdalla Omer, Hemn
    et al.
    Department of Microbiology/Immunology, College of Medicine, University of Suleimani, Sulaymaniyah, Iraq.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Amin, Kawa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Department of Microbiology/Immunology, College of Medicine, University of Suleimani, Sulaymaniyah, Iraq.
    The role of inflammatory and remodelling biomarkers in patients with non-small cell lung cancer2023In: Central European Journal of Immunology, ISSN 1426-3912, E-ISSN 1644-4124, Vol. 48, no 4, p. 330-337Article in journal (Refereed)
    Abstract [en]

    Introduction:

    Biomarkers play a crucial role in evaluating the prognosis, diagnosis, and monitoringof non-small cell lung cancer (NSCLC). The aim of this study was to compare the levels of inflammatoryand remodelling biomarkers among patients with NSCLC and healthy controls (HCs) and to investigatethe correlation between these biomarkers.

    Material and methods:

    Blood samples were taken from 93 NSCLC and 84 HCs. Each sample wasanalysed for the inflammatory biomarkers transforming growth factor β1 (TGF-β1), mothers againstdecapentaplegic homolog 2 (SMAD2) and the remodelling biomarkers Wingless-related integration site(Wnt3a) and β-catenin (CTNN-β1).

    Results:

    The patients with NSCLC had significantly higher levels of all the measured biomarkers.In the NSCLC patients, TGF-β1 correlated significantly with SMAD2 (r = 0.34, p = 0.0008), Wnt3a(r = 0.328, p = 0.0013), and CTNN-β1 levels (r = 0.30, p = 0.004). SMAD2 correlated significantlywith CTNN-β1 (r = 0.546, p = 0.0001) and Wnt3a (r = 0.598, p = 0.0001). CTNN-β1 level also correlated with the level of Wnt3a (r = 0.61, p = 0.0001). No correlation was found between biomarkersand symptom scores.

    Discussion:

    In this study, patients with NSCLC had higher inflammatory and remodelling biomarker levels than HCs. In the NSCLC, there were significant associations between inflammatory andremodelling biomarkers. This indicates that measuring biomarkers could be valuable in the workupof NSCLC patients.

    Conclusions:

    Our investigation showed that inflammatory and remodelling biomarkers might playa role in future immunologic response and pharmacologically targeted NSCLC therapy.

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    Lung Cancer
  • 4.
    Abdelrazak Morsy, Mohammad Hamdy
    et al.
    Karolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Alexandria Univ, Med Res Inst, Dept Appl Med Chem, Alexandria, Egypt.;Karolinska Inst, Lab Med, Alfred Nobels Alle 8B, S-14152 Stockholm, Sweden..
    Lilienthal, Ingrid
    Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Solna, Sweden..
    Lord, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Merrien, Magali
    Karolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Wasik, Agata Magdalena
    Karolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Sureda-Gómez, Marta
    Inst Invest Biomed August Pi Sunyer, Barcelona, Spain..
    Amador, Virginia
    Inst Invest Biomed August Pi Sunyer, Barcelona, Spain.;Ctr Invest Biomed Red Canc, Madrid, Spain..
    Johansson, Henrik J.
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Lehtiö, Janne
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Garcia-Torre, Beatriz
    Inst Invest Biomed August Pi Sunyer, Barcelona, Spain..
    Martin-Subero, Jose Ignacio
    Inst Invest Biomed August Pi Sunyer, Barcelona, Spain.;Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain..
    Tsesmetzis, Nikolaos
    Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Solna, Sweden..
    Tao, Sijia
    Emory Univ, Ctr Viro Sci & Cure, Sch Med, Dept Pediat, Atlanta, GA USA..
    Schinazi, Raymond F.
    Emory Univ, Ctr Viro Sci & Cure, Sch Med, Dept Pediat, Atlanta, GA USA..
    Kim, Baek
    Emory Univ, Ctr Viro Sci & Cure, Sch Med, Dept Pediat, Atlanta, GA USA..
    Sorteberg, Agnes L.
    Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Solna, Sweden..
    Wickström, Malin
    Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Solna, Sweden..
    Sheppard, Devon
    Francis Crick Inst, Macromol Struct Lab, London, England..
    Rassidakis, Georgios Z.
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX USA..
    Taylor, Ian A.
    Francis Crick Inst, Macromol Struct Lab, London, England..
    Christensson, Birger
    Karolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Campo, Elias
    Inst Invest Biomed August Pi Sunyer, Barcelona, Spain.;Ctr Invest Biomed Red Canc, Madrid, Spain.;Univ Barcelona, Hosp Clin Barcelona, Dept Anat Pathol, Hematopathol Sect, Barcelona, Spain..
    Herold, Nikolas
    Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Solna, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Paediat Oncol, Stockholm, Sweden..
    Sander, Birgitta
    Karolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    SOX11 is a novel binding partner and endogenous inhibitor of SAMHD1 ara-CTPase activity in mantle cell lymphoma2024In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 143, no 19, p. 1953-1964Article in journal (Refereed)
    Abstract [en]

    Sterile alpha motif and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara -C) resistance in several hematological malignancies. Targeting SAMHD1's ara-CTPase activity has recently been demonstrated to enhance ara -C ef fi cacy in acute myeloid leukemia. Here, we identify the transcription factor SRY-related HMGbox containing protein 11 (SOX11) as a novel direct binding partner and fi rst known endogenous inhibitor of SAMHD1. SOX11 is aberrantly expressed not only in mantle cell lymphoma (MCL), but also in some Burkitt lymphomas. Coimmunoprecipitation of SOX11 followed by mass spectrometry in MCL cell lines identi fi ed SAMHD1 as the top SOX11 interaction partner, which was validated by proximity ligation assay. In vitro, SAMHD1 bound to the HMG box of SOX11 with low-micromolar af fi nity. In situ crosslinking studies further indicated that SOX11-SAMHD1 binding resulted in a reduced tetramerization of SAMHD1. Functionally, expression of SOX11 inhibited SAMHD1 ara-CTPase activity in a dose-dependent manner resulting in ara -C sensitization in cell lines and in a SOX11-inducible mouse model of MCL. In SOX11-negative MCL, SOX11-mediated ara-CTPase inhibition could be mimicked by adding the recently identi fi ed SAMHD1 inhibitor hydroxyurea. Taken together, our results identify SOX11 as a novel SAMHD1 interaction partner and its fi rst known endogenous inhibitor with potentially important implications for clinical therapy strati fi cation.

  • 5. Abdulla, Maysaa
    et al.
    Hollander, Peter
    Pandzic, Tatjana
    Mansouri, Larry
    Ednersson, Susanne Bram
    Andersson, Per-Ola
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Fors, Maja
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Erlanson, Martin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Petersen, Helga Munch
    Asmar, Fazila
    Gronbaek, Kirsten
    Enblad, Gunilla
    Cavelier, Lucia
    Rosenquist, Richard
    Amini, Rose-Marie
    Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma2020In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 95, no 1, p. 57-67Article in journal (Refereed)
    Abstract [en]

    The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated B-cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO). However, GEP is not widely applied in clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was to evaluate the concordance of COO assignment between the Lymph2Cx GEP assay and the IHC-based Hans algorithm, to decide which model is the best survival predictor. Both GEP and IHC were performed in 359 homogenously treated Swedish and Danish DLBCL patients, in a retrospective multicenter cohort. The overall concordance between GEP and IHC algorithm was 72%; GEP classified 85% of cases assigned as GCB by IHC, as GCB, while 58% classified as non-GCB by IHC, were categorized as ABC by GEP. There were significant survival differences (overall survival and progression-free survival) if cases were classified by GEP, whereas if cases were categorized by IHC only progression-free survival differed significantly. Importantly, patients assigned as non-GCB/ABC both by IHC and GEP had the worst prognosis, which was also significant in multivariate analyses. Double expression of MYC and BCL2 was more common in ABC cases and was associated with a dismal outcome. In conclusion, to determine COO both by IHC and GEP is the strongest outcome predictor to identify DLBCL patients with the worst outcome.

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  • 6.
    Abdulla, Maysaa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Hollander, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Pandzic, Tatjana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Mansouri, Larry
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Ednersson, Susanne Bram
    Sahlgrens Univ Hosp, Dept Pathol, Gothenburg, Sweden.
    Andersson, Per-Ola
    Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden;Sodra Alvsborg Hosp Borås, Dept Med, Borås, Sweden.
    Hultdin, Magnus
    Umeå Univ, Dept Med Biosci, Pathol, Umeå, Sweden.
    Fors, Maja
    Umeå Univ, Dept Med Biosci, Pathol, Umeå, Sweden.
    Erlanson, Martin
    Umeå Univ, Dept Radiat Sci, Oncol, Umeå, Sweden.
    Degerman, Sofie
    Umeå Univ, Dept Med Biosci, Pathol, Umeå, Sweden.
    Petersen, Helga Munch
    Copenhagen Univ Hosp, Dept Pathol, Rigshosp, Copenhagen, Denmark.
    Asmar, Fazila
    Copenhagen Univ Hosp, Dept Hematol, Rigshosp, Copenhagen, Denmark.
    Gronbaek, Kirsten
    Copenhagen Univ Hosp, Dept Hematol, Rigshosp, Copenhagen, Denmark.
    Enblad, Gunilla
    Uppsala Univ, Expt & Clin Oncol, Dept Immunol Genet & Pathol, Uppsala, Sweden.
    Cavelier, Lucia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Rosenquist, Richard
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma2020In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 95, no 1, p. 57-67Article in journal (Refereed)
    Abstract [en]

    The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated B-cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO). However, GEP is not widely applied in clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was to evaluate the concordance of COO assignment between the Lymph2Cx GEP assay and the IHC-based Hans algorithm, to decide which model is the best survival predictor. Both GEP and IHC were performed in 359 homogenously treated Swedish and Danish DLBCL patients, in a retrospective multicenter cohort. The overall concordance between GEP and IHC algorithm was 72%; GEP classified 85% of cases assigned as GCB by IHC, as GCB, while 58% classified as non-GCB by IHC, were categorized as ABC by GEP. There were significant survival differences (overall survival and progression-free survival) if cases were classified by GEP, whereas if cases were categorized by IHC only progression-free survival differed significantly. Importantly, patients assigned as non-GCB/ABC both by IHC and GEP had the worst prognosis, which was also significant in multivariate analyses. Double expression of MYC and BCL2 was more common in ABC cases and was associated with a dismal outcome. In conclusion, to determine COO both by IHC and GEP is the strongest outcome predictor to identify DLBCL patients with the worst outcome.

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    fulltext
  • 7.
    Abedi, Mohammad R.
    et al.
    Örebro University Hospital. Department of Laboratory Medicine, Section for Transfusion Medicine.
    Doverud, Ann-Charlotte
    Department of Laboratory Medicine, Section for Transfusion Medicine, Örebro University Hospital. Örebro, Sweden.
    Preparation and Pathogen Inactivation of Double Dose Buffy Coat Platelet Products using the INTERCEPT Blood System2012In: Journal of Visualized Experiments, E-ISSN 1940-087X, no 70, article id UNSP e4414Article in journal (Refereed)
    Abstract [en]

    Blood centers are faced with many challenges including maximizing production yield from the blood product donations they receive as well as ensuring the highest possible level of safety for transfusion patients, including protection from transfusion transmitted diseases. This must be accomplished in a fiscally responsible manner which minimizes operating expenses including consumables, equipment, waste, and personnel costs, among others.

    Several methods are available to produce platelet concentrates for transfusion. One of the most common is the buffy coat method in which a single therapeutic platelet unit (>= 2.0 x10(11) platelets per unit or per local regulations) is prepared by pooling the buffy coat layer from up to six whole blood donations. A procedure for producing "double dose" whole blood derived platelets has only recently been developed.

    Presented here is a novel method for preparing double dose whole blood derived platelet concentrates from pools of 7 buffy coats and subsequently treating the double dose units with the INTERCEPT Blood System for pathogen inactivation. INTERCEPT was developed to inactivate viruses, bacteria, parasites, and contaminating donor white cells which may be present in donated blood. Pairing INTERCEPT with the double dose buffy coat method by utilizing the INTERCEPT Processing Set with Dual Storage Containers (the "DS set"), allows blood centers to treat each of their double dose units in a single pathogen inactivation processing set, thereby maximizing patient safety while minimizing costs. The double dose buffy coat method requires fewer buffy coats and reduces the use of consumables by up to 50% (e.g. pooling sets, filter sets, platelet additive solution, and sterile connection wafers) compared to preparation and treatment of single dose buffy coat platelet units. Other cost savings include less waste, less equipment maintenance, lower power requirements, reduced personnel time, and lower collection cost compared to the apheresis technique.

  • 8.
    Abildgaard, Niels
    et al.
    Hematology Research Unit, Department of Hematology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
    Anttila, Pekka
    Comprehensive Cancer Center, Department of Hematology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
    Waage, Anders
    Department of Hematology, St Olav's University Hospital, Trondheim, Norway.
    Rubin, Katrine Hass
    Research Unit OPEN, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
    Ørstavik, Sigurd
    Takeda Pharmaceuticals International AG, Oslo, Norway.
    Bent-Ennakhil, Nawal
    Takeda Pharmaceuticals International AG, Zurich, Switzerland.
    Gavini, François
    Takeda Pharmaceuticals International AG, Zurich, Switzerland.
    Ma, Yuanjun
    Parexel International, Stockholm, Sweden.
    Freilich, Jonatan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Parexel International, Stockholm, Sweden.
    Hansson, Markus
    Sahlgrenska Academy and Sahlgrenska University Hospital, Göteborg, Sweden.
    Real-world treatment patterns and outcomes for patients with multiple myeloma in Denmark, Finland and Sweden: An analysis using linked Nordic registries2024In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 201, article id 113921Article in journal (Refereed)
    Abstract [en]

    Aim: The Health outcomes and Understanding of MyelomA multi-National Study (HUMANS) was a large-scale, retrospective study conducted across Denmark, Finland and Sweden using linked data from national registries. We describe the characteristics, treatment patterns and clinical outcomes for patients with newly diagnosed multiple myeloma (NDMM) over 2010–2018.

    Methods: Patients with NDMM who received MM-specific, first-line treatments, were categorised by treatment (autologous stem cell transplantation [ASCT] or a combination chemotherapy regimen based on bortezomib, lenalidomide or melphalan-prednisolone-thalidomide).

    Results: 11,023 patients received treatment over 2010–2018. Time between diagnosis and treatment was shortest in Denmark (0.9 months), then Sweden (2.9 months) and Finland (4.6 months). Around one third of patients underwent ASCT. Lenalidomide-based regimens were prescribed to 23–28% of patients in Denmark and Finland, versus 12% in Sweden. Patients receiving lenalidomide had the longest wait for treatment, from 3.2 months (Denmark) to 12.1 months (Sweden). Treatment persistence was highest among patients receiving melphalan-prednisolone-thalidomide (7–8 months) in Finland and Sweden and lowest among those receiving bortezomib (3.5 months) in Finland. Overall survival (OS) was longest among patients with ASCT (7–10 years). Among patients receiving chemotherapy, OS (from diagnosis/treatment initiation), varied between cohorts. In a sensitivity analysis excluding patients with smouldering MM, OS decreased for all; for patients receiving bortezomib or lenalidomide, OS from diagnosis was 40–49 and 27–54 months, respectively.

    Conclusions: This population-based study of patients with NDMM receiving first-line MM-specific treatment, provides real-world data on treatment patterns and outcomes to complement data from randomised clinical trials.

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  • 9.
    Abrantes, João A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Solms, Alexander
    Garmann, Dirk
    Nielsen, Elisabet I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Jönsson, Siv
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Karlsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Relationship between factor VIII activity, bleeds and individual characteristics in severe hemophilia A patients2020In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 105, no 5, p. 1443-1453Article in journal (Refereed)
    Abstract [en]

    Pharmacokinetic-based prophylaxis of replacement factor VIII products has been encouraged in the past years, but the exposure (factor VIII activity)-response (bleeding frequency) relationship remains unclear. The aim of this study was to characterize the relationship between factor VIII dose, plasma factor VIII activity, bleeding patterns and individual characteristics in severe hemophilia A patients. Pooled pharmacokinetic and bleeding data during prophylactic treatment with BAY 81-8973 (octocog alfa) were obtained from the three LEOPOLD trials. The population pharmacokinetics of factor VIII activity and longitudinal bleeding frequency, as well as bleeding severity, were described using nonlinear mixed effects modelling in NONMEM. In total, 183 patients (median age 22 years [range, 1-61]; weight 60 kg [11-124]) contributed with 1535 plasma factor VIII activity observations, 633 bleeds and 11 patient/study characteristics (median observation period 12 months [3.1-13.1]). A parametric repeated time-to-categorical bleed model, guided by plasma factor VIII activity from a 2-compartment population pharmacokinetic model, described the time to the occurrence of bleeds and their severity. Bleeding probability decreased with time of study, and a bleed was not found to affect the time of the next bleed. Several covariate effects were identified, including the bleeding history in the 12-month pre-study period increasing the bleeding hazard. However, unexplained inter-patient variability for the phenotypic bleeding pattern remained large (111%CV). Further studies to translate the model into a tool for dose individualization that considers the individual bleeding risk are required. Research based on a post-hoc analysis of the LEOPOLD studies (ClinicalTrials.gov identifiers NCT01029340, NCT01233258 and NCT01311648).

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  • 10. Achouiti, A.
    et al.
    Vogl, T.
    Urban, Constantin
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Hommes, T. J.
    van Zoelen, M. A.
    Florquin, S.
    Roth, J.
    van 't Veer, C.
    de Vos, A. F.
    van der Poll, T.
    Myeloid related protein (mrp) 8/14 contributes to an antibacterial host response against klebsiella (k.) pneumoniae2012In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 37, no S1, p. 56-56Article in journal (Other academic)
  • 11.
    Acosta, Stefan
    et al.
    Vascular Center, Skåne University Hospital, Malmö, Sweden.
    Nilsson, Torbjörn
    Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
    Current status on plasma biomarkers for acute mesenteric ischemia2012In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 33, no 4, p. 355-361Article, review/survey (Refereed)
    Abstract [en]

    Clinical diagnosis of acute mesenteric ischemia is difficult. The aim of this review is to provide current status on the search for an accurate plasma biomarker for acute mesenteric ischemia. A search using the medical subject heading terms marker and mesenteric ischemia or intestinal ischemia or superior mesenteric artery occlusion or mesenteric venous thrombosis in the Medline and Embase databases from 1980 to 2011. Studies without a control group or a control group consisted of healthy individuals (human studies), or studies on intestinal reperfusion were excluded. Twenty animal and twelve human studies were identified. In human studies, the studied series of patients had a control group that had a need of laparotomy (n = 2), suspected acute mesenteric ischemia (n = 7), acute abdomen (n = 2) or systemic inflammatory response syndrome (n = 1). D: -dimer has been found to be the most consistent highly sensitive early marker, but specificity was low. The follow-up study on α-glutathione S-transferase yielded inferior sensitivity and accuracy than the preliminary study, clearly questioning the value of this marker. Intestinal fatty acid binding globulin (I-FABP) and D: -lactate are both interesting markers, but the results were conflicting. Different cut-off levels have been used in the studies on I-FABP. The encouraging preliminary result of cobalt-albumin and urinary FABP as an accurate marker needs to be addressed in other study populations. The early clinical and laboratory diagnosis of intestinal ischemia remains a challenge. None of the proposed plasma-derived tests for acute mesenteric ischemia has as yet entered routine clinical practice. The proposed biomarkers need to be evaluated in a prospective clinical research project in patients with acute abdomen.

  • 12. Acosta, Stefan
    et al.
    Nilsson, Torbjörn K
    Department of Clinical Chemistry, Örebro University Hospital.
    Current status on plasma biomarkers for acute mesenteric ischemia2012In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 33, no 4, p. 355-361Article in journal (Refereed)
    Abstract [en]

    Clinical diagnosis of acute mesenteric ischemia is difficult. The aim of this review is to provide current status on the search for an accurate plasma biomarker for acute mesenteric ischemia. A search using the medical subject heading terms marker and mesenteric ischemia or intestinal ischemia or superior mesenteric artery occlusion or mesenteric venous thrombosis in the Medline and Embase databases from 1980 to 2011. Studies without a control group or a control group consisted of healthy individuals (human studies), or studies on intestinal reperfusion were excluded. Twenty animal and twelve human studies were identified. In human studies, the studied series of patients had a control group that had a need of laparotomy (n = 2), suspected acute mesenteric ischemia (n = 7), acute abdomen (n = 2) or systemic inflammatory response syndrome (n = 1). D: -dimer has been found to be the most consistent highly sensitive early marker, but specificity was low. The follow-up study on α-glutathione S-transferase yielded inferior sensitivity and accuracy than the preliminary study, clearly questioning the value of this marker. Intestinal fatty acid binding globulin (I-FABP) and D: -lactate are both interesting markers, but the results were conflicting. Different cut-off levels have been used in the studies on I-FABP. The encouraging preliminary result of cobalt-albumin and urinary FABP as an accurate marker needs to be addressed in other study populations. The early clinical and laboratory diagnosis of intestinal ischemia remains a challenge. None of the proposed plasma-derived tests for acute mesenteric ischemia has as yet entered routine clinical practice. The proposed biomarkers need to be evaluated in a prospective clinical research project in patients with acute abdomen.

  • 13.
    Adoberg, Annika
    et al.
    North Estonia Med Ctr, Estonia.
    Paats, Joosep
    Tallinn Univ Technol, Estonia.
    Arund, Jurgen
    Tallinn Univ Technol, Estonia.
    Dhondt, Annemieke
    Ghent Univ Hosp, Belgium.
    Fridolin, Ivo
    Tallinn Univ Technol, Estonia.
    Glorieux, Griet
    Ghent Univ Hosp, Belgium.
    Holmar, Jana
    Tallinn Univ Technol, Estonia.
    Lauri, Kai
    Synlab Eesti OU, Estonia.
    Leis, Liisi
    North Estonia Med Ctr, Estonia.
    Luman, Merike
    North Estonia Med Ctr, Estonia; Tallinn Univ Technol, Estonia.
    Pilt, Kristjan
    Tallinn Univ Technol, Estonia.
    Uhlin, Fredrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Tallinn Univ Technol, Estonia.
    Tanner, Risto
    Tallinn Univ Technol, Estonia.
    Treatment with Paracetamol Can Interfere with the Intradialytic Optical Estimation in Spent Dialysate of Uric Acid but Not of Indoxyl Sulfate2022In: Toxins, E-ISSN 2072-6651, Vol. 14, no 9, article id 610Article in journal (Refereed)
    Abstract [en]

    Optical online methods are used to monitor the haemodialysis treatment efficiency of end stage kidney disease (ESKD) patients. The aim of this study was to analyse the effect of the administration of UV-absorbing drugs, such as paracetamol (Par), on the accuracy of optical monitoring the removal of uremic toxins uric acid (UA) and indoxyl sulfate (IS) during standard haemodialysis (HD) and haemodiafiltration (HDF) treatments. Nine patients received Par in daily dosages 1-4 g for 30 sessions. For 137 sessions, in 36 patients the total daily dosage of UV-absorbing drugs was less than 500 mg, and for 6 sessions 3 patients received additional UV-absorbing drugs. Par administration slightly affected the accuracy of optically assessed removal of UA expressed as bias between optically and laboratory-assessed reduction ratios (RR) during HD but not HDF employing UV absorbance of spent dialysate (p &lt; 0.05) at 295 nm wavelength with the strongest correlation between the concentration of UA and absorbance. Corresponding removal of IS based on fluorescence at Ex280/Em400 nm during HD and HDF was not affected. Administration of UV-absorbing drugs may in some settings influence the accuracy of optical assessments in spent dialysate of the removal of uremic solutes during haemodialysis treatment of ESKD patients.

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  • 14.
    Afram, G.
    et al.
    Karolinska Inst, Med, Stockholm, Sweden..
    Watz, E.
    ONK PAT, Ctr Apheresis, Stockholm, Sweden..
    Remberger, M.
    ONK PAT, Ctr Allogene Stem Cell Transplantat, Immunol, Stockholm, Sweden..
    Axdorph-Nygell, U.
    ONK PAT, Ctr Apheresis, Stockholm, Sweden..
    Sundin, M.
    Karolinska Inst, Pediat Haematol, Stockholm, Sweden..
    Hagglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Mattsson, J.
    Karolinska Inst, Ctr Stem Cell Transplantat, Stockholm, Sweden..
    Uhlin, M.
    Karolinska Inst, Ctr Stem Cell Transplantat, Stockholm, Sweden..
    Extracorporeal photopheresis as treatment for moderate-severe chronic graft-versus-host disease2016In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 51, p. S138-S138Article in journal (Other academic)
  • 15.
    Afram, Gabriel
    et al.
    Karolinska Univ Hosp Huddinge, Dept Hematol, Stockholm, Sweden.
    Perez Simon, Jose Antonio
    Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Dept Hematol,Inst Biomed Sevilla IBIS, Seville, Spain.
    Remberger, Mats
    Karolinska Univ Hosp Huddinge, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden.
    Caballero-Velazquez, Teresa
    Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Dept Hematol,Inst Biomed Sevilla IBIS, Seville, Spain.
    Martino, Rodrigo
    Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain.
    Luis Pinana, Jose
    Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain;Hosp Clin Univ, Dept Hematol, Valencia, Spain.
    Ringden, Olle
    Karolinska Univ Hosp Huddinge, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden.
    Esquirol, Albert
    Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain.
    Lopez-Corral, Lucia
    Hosp Univ Salamanca IBSAL, Dept Hematol, Salamanca, Spain.
    Garcia, Irene
    Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain.
    Lopez-Godino, Oriana
    Hosp Univ Salamanca IBSAL, Dept Hematol, Salamanca, Spain.
    Sierra, Jordi
    Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain.
    Caballero, Dolores
    Hosp Univ Salamanca IBSAL, Dept Hematol, Salamanca, Spain.
    Ljungman, Per
    Vazquez, Lourdes
    Hosp Univ Salamanca IBSAL, Dept Hematol, Salamanca, Spain.
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Reduced intensity conditioning increases risk of severe cGVHD: identification of risk factors for cGVHD in a multicenter setting2018In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 35, no 6, article id 79Article in journal (Refereed)
    Abstract [en]

    Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Aim is to identify risk factors for the development of cGVHD in a multicenter setting. Patients transplanted between 2000 and 2006 were analyzed (n = 820). Donors were HLA-identical siblings (57%), matched unrelated donors (30%), and HLA-A, B or DR antigen mismatched (13%). Reduced intensity conditioning (RIC) was given to 65% of patients. Overall incidence of cGVHD was 46% for patients surviving more than 100 days after HSCT (n = 747). Older patient age [HR 1.15, p < 0.001], prior acute GVHD [1.30, p = 0.024], and RIC [1.36, p = 0.028] increased overall cGVHD. In addition, RIC [4.85, p < 0.001], prior aGVHD [2.14, p = 0.001] and female donor to male recipient [1.80, p = 0.008] increased the risk of severe cGVHD. ATG had a protective effect for both overall [0.41, p < 0.001] and severe cGVHD [0.20, p < 0.001]. Relapse-free survival (RFS) was impaired in patients with severe cGVHD. RIC, prior aGVHD, and female-to-male donation increase the risk of severe cGVHD. ATG reduces the risk of all grades of cGVHD without hampering RFS. GVHD prophylaxis may be tailored according to the risk profile of patients.

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  • 16.
    Afram, Gabriel
    et al.
    Karolinska Univ Lab, Hematol Ctr, Stockholm, Sweden;Karolinska Inst, Div Hematol, Dept Med, Stockholm, Sweden.
    Watz, Emma
    Karolinska Univ Lab, Dept Clin Immunol & Transfus Med, Stockholm, Sweden;Karolinska Inst, Div Transplantat Surg, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Remberger, Mats
    Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden;Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
    Nygell, Ulla Axdorph
    Karolinska Univ Lab, Hematol Ctr, Stockholm, Sweden;Karolinska Univ Lab, Dept Clin Immunol & Transfus Med, Stockholm, Sweden;Karolinska Inst, Div Transplantat Surg, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Sundin, Mikael
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Hematol Immunol SCT Sect, Stockholm, Sweden;Karolinska Inst, Div Pediat, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Hägglund, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Mattsson, Jonas
    Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden;Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
    Uhlin, Michael
    Karolinska Univ Lab, Dept Clin Immunol & Transfus Med, Stockholm, Sweden;Karolinska Inst, Div Transplantat Surg, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Higher response rates in patients with severe chronic skin graft-versus-host disease treated with extracorporeal photopheresis2019In: Central European Journal of Immunology, ISSN 1426-3912, E-ISSN 1644-4124, Vol. 44, no 1, p. 84-91Article in journal (Refereed)
    Abstract [en]

    Introduction: Different forms of graft-versus-host disease (GVHD) remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The prognosis for steroid-refractory chronic GVHD (cGVHD) remains poor. Our aim was to evaluate extracorporeal photopheresis (ECP) treatment in cGVHD patients with different organ involvement to detect subgroups of patients with the best response.

    Material and methods: Thirty-four patients who underwent HSCT and developed moderate (n = 7) or severe (n = 27) steroid-refractory or steroid-dependent cGVHD treated with ECP were included in the analysis. A matched cGVHD control patient group untreated with ECP was collected for comparison.

    Results: Compared to the control group and the stable/progressive disease (SD/PD) patients, individuals with complete/partial remission have higher overall survival and lower transplant-related mortality. Furthermore, patients with complete and partial remission (CR/PR) had significantly higher levels of albumin and platelets after ECP treatment compared to patients with stable or progressive cGVHD (SD/PD). Corticosteroid treatment and other immunosuppressive agents could successfully be tapered in the CR/PR group compared to the SD/PD patients. In this study patients with skin cGVHD are those with the highest rate of CR/PR after ECP treatment.

    Conclusions: Our results suggest that ECP treatment is safe and effective for patients with predominantly skin, oral and liver cGVHD.

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  • 17.
    Agarwal, Prasoon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Kalushkova, Antonia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Enroth, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Alzrigat, Mohammad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Osterborg, Anders
    Nilsson, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Öberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Jernberg-Wiklund, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    An Epigenomic Map of Multiple Myeloma Reveals the Importance of Polycomb Gene Silencing for the Malignancy2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 18.
    Agathangelidis, A.
    et al.
    Ist Sci San Raffaele, Div Expt Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, I-20132 Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Bystry, V.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Hadzidimitriou, A.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Sutton, L. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Minga, E.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Kienle, D.
    Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany..
    Davis, Z.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Yan, X. J.
    North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Shanafelt, T.
    Mayo Clin, Dept Med, Dept Hematol, Rochester, MN USA..
    Boudjogra, M.
    Univ Paris 06, Hop Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Hop Pitie Salpetriere, Paris, France..
    Plevova, K.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Gounari, M.
    Ist Sci San Raffaele, Div Expt Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, I-20132 Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Xochelli, A.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Navarro, A.
    Univ Barcelona, IDIBAPS, Unidad Hematopatol, Serv Anat Patol, Barcelona, Spain..
    Chatzouli, M.
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Pedersen, L. B.
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Scarfo, L.
    Ist Sci San Raffaele, Div Expt Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, I-20132 Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Rossi, D.
    Amedeo Avogadro Univ Eastern Piedmont, Dept Hematol, Novara, Italy..
    Veronese, S.
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Hematol, Milan, Italy..
    Facco, M.
    Univ Padua, Sch Med, Hematol & Clin Immunol Branch, Dept Med, Padua, Italy..
    Bikos, V.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Karan-Djurasevic, T.
    Univ Belgrade, Inst Mol Genet & Genet Engn, Belgrade, Serbia..
    Pavlovic, S.
    Univ Kragujevac, Kragujevac, Serbia..
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Poiron, C.
    Univ Montpellier, IMGT, LIGM, IGH, Montpellier, France..
    Chu, C. C.
    North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Stalika, E.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Giudicelli, V.
    Univ Montpellier, IMGT, LIGM, IGH, Montpellier, France..
    Panagiotidis, P.
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Sudarikov, A.
    Natl Hematol Res Ctr, Dept Mol Hematol, Moscow, Russia..
    Anagnostopoulos, A.
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Trentin, L.
    Univ Padua, Sch Med, Hematol & Clin Immunol Branch, Dept Med, Padua, Italy..
    Catherwood, M.
    Belfast City Hosp, Dept Hematooncol, Belfast BT9 7AD, Antrim, North Ireland..
    Montillo, M.
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Hematol, Milan, Italy..
    Gaidano, G.
    Amedeo Avogadro Univ Eastern Piedmont, Dept Hematol, Novara, Italy..
    Campo, E.
    Univ Barcelona, IDIBAPS, Unidad Hematopatol, Serv Anat Patol, Barcelona, Spain..
    Geisler, C. H.
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Langerak, A. W.
    Erasmus MC, Univ Med Ctr, Dept Immunol, Rotterdam, Netherlands..
    Pospisilova, S.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Lefranc, M. P.
    Univ Montpellier, IMGT, LIGM, IGH, Montpellier, France..
    Chiorazzi, N.
    North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Oscier, D.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Jelinek, D. F.
    Mayo Clin, Dept Immunol, Rochester, MN USA..
    Stilgenbauer, S.
    Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany..
    Belessi, C.
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Davi, F.
    Univ Paris 06, Hop Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Hop Pitie Salpetriere, Paris, France..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ghia, P.
    Ist Sci San Raffaele, Div Expt Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, I-20132 Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Darzentas, N.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. CERTH, Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    HIGHER-ORDER IMMUNOGLOBULIN SEQUENCE RELATIONS FOR MAJOR SUBSETS OF CHRONIC LYMPHOCYTIC LEUKEMIA: UNIQUENESS VERSUS EQUIVALENCE2015In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, p. 47-48Article in journal (Other academic)
  • 19.
    Agathangelidis, Andreas
    et al.
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece..
    Chatzidimitriou, Anastasia
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Gemenetzi, Katerina
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece.;Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece..
    Giudicelli, Veronique
    Univ Montpellier, Ctr Natl Rech Sci CNRS, Inst Genet Humaine IGH, Unite Mixte Rech UMR, Montpellier, France..
    Karypidou, Maria
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece..
    Plevova, Karla
    Masaryk Univ, Fac Med, Dept Internal Med Hematol & Oncol, Univ Hosp Brno, Brno, Czech Republic.;Masaryk Univ, Ctr Mol Med, Cent European Inst Technol, Brno, Czech Republic..
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Yan, Xiao-Jie
    Feinstein Inst Med Res, Northwell Hlth, Manhasset, NY USA..
    Jeromin, Sabine
    MLL Munich Leukemia Lab, Munich, Germany..
    Schneider, Christof
    Univ Hosp Med Ctr, Ulm, Germany..
    Pedersen, Lone Bredo
    Copenhagen Univ Hosp, Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Tschumper, Renee C.
    Mayo Clin, Dept Immunol, Rochester, MN USA..
    Sutton, Lesley-Ann
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Baliakas, Panagiotis
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Scarfo, Lydia
    Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Strateg Res Program CLL,Ist Ricovero & Cura Carat, Milan, Italy..
    van Gastel, Ellen J.
    Univ Med Ctr UMC, Dept Immunol, Lab Med Immunol, Erasmus MC, Rotterdam, Netherlands..
    Armand, Marine
    Sorbonne Univ, Ctr Rech Cordeliers, Dept Biol Hematol, Hop Pitie Salpetriere,AP HP,UMR S 1138, Paris, France..
    Tausch, Eugen
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Biderman, Bella
    Natl Res Ctr Hematol, Moscow, Russia..
    Baer, Constance
    MLL Munich Leukemia Lab, Munich, Germany..
    Bagnara, Davide
    Univ Genoa, Dept Expt Med, Genoa, Italy..
    Navarro, Alba
    Ctr Invest Biomed Red Oncol CIBERONC, Madrid, Spain.;Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain..
    de Septenville, Anne Langlois
    Sorbonne Univ, Ctr Rech Cordeliers, Dept Biol Hematol, Hop Pitie Salpetriere,AP HP,UMR S 1138, Paris, France..
    Guido, Valentina
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Haematol Dept, Mol Pathol Unit, Milan, Italy..
    Mitterbauer-Hohendanner, Gerlinde
    Med Univ Vienna, Dept Lab Med, Vienna, Austria..
    Dimovski, Aleksandar
    Ss Cyril & Methodius Univ Skopje, Fac Pharm, Skopje, North Macedonia..
    Brieghel, Christian
    Copenhagen Univ Hosp, Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Lawless, Sarah
    Belfast City Hosp, Clin Haematol, Belfast Hlth & Social Care Trust, Belfast, Antrim, North Ireland..
    Meggendorfer, Manja
    MLL Munich Leukemia Lab, Munich, Germany..
    Brazdilova, Kamila
    Masaryk Univ, Fac Med, Dept Internal Med Hematol & Oncol, Univ Hosp Brno, Brno, Czech Republic.;Masaryk Univ, Ctr Mol Med, Cent European Inst Technol, Brno, Czech Republic..
    Ritgen, Matthias
    Univ Hosp Schleswig Holstein, Med Dept 2, Campus Kiel, Kiel, Germany..
    Facco, Monica
    Univ Padua, Dept Med DIMED, Hematol & Clin Immunol Unit, Padua, Italy.;Veneto Inst Mol Med, Padua, Italy..
    Tresoldi, Cristina
    Ist Sci San Raffaele, Div Immunol Transplantat & Infect Dis, IRCCS, Milan, Italy..
    Visentin, Andrea
    Univ Padua, Dept Med DIMED, Hematol & Clin Immunol Unit, Padua, Italy.;Veneto Inst Mol Med, Padua, Italy..
    Patriarca, Andrea
    Univ Eastern Piedmont Osped Maggiore Carita, Dept Translat Med, Div Hematol, Novara, Italy..
    Catherwood, Mark
    Belfast City Hosp, Clin Haematol, Belfast Hlth & Social Care Trust, Belfast, Antrim, North Ireland..
    Bonello, Lisa
    Azienda Osped Univ AOU, City Hlth & Sci Turin, Gen Anatomopathol & Mol Oncogenet, Turin, Italy..
    Sudarikov, Andrey
    Natl Res Ctr Hematol, Moscow, Russia..
    Vanura, Katrina
    Med Univ Vienna, Dept Lab Med, Vienna, Austria..
    Roumelioti, Maria
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Francova, Hana Skuhrova
    Masaryk Univ, Fac Med, Dept Internal Med Hematol & Oncol, Univ Hosp Brno, Brno, Czech Republic..
    Moysiadis, Theodoros
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece..
    Veronese, Silvio
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Haematol Dept, Mol Pathol Unit, Milan, Italy..
    Giannopoulos, Krzysztof
    Med Univ Lublin, Expt Hematooncol Dept, Lublin, Poland..
    Mansouri, Larry
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Karan-Djurasevic, Teodora
    Univ Belgrade, Inst Mol Genet & Genet Engn, Belgrade, Serbia..
    Sandaltzopoulos, Raphael
    Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece..
    Bodor, Csaba
    Semmelweis Univ, Dept Pathol & Expt Canc Res 1, MTA SE Momentum Mol Oncohematol Res Grp, Budapest, Hungary..
    Fais, Franco
    Univ Genoa, Dept Expt Med, Genoa, Italy.;IRCCS Osped Policlin San Martino, UO Mol Pathol, Genoa, Italy..
    Kater, Arnon
    Univ Amsterdam, Amsterdam UMC, Amsterdam Infect & Immun Inst, Dept Hematol,Canc Ctr Amsterdam, Amsterdam, Netherlands..
    Panovska, Irina
    Ss Cyril & Methodius Univ Skopje, Fac Med, Dept Hematol, Skopje, North Macedonia..
    Rossi, Davide
    Inst Southern Switzerland, Div Hematol Oncol, Bellinzona, Switzerland..
    Alshemmari, Salem
    Kuwait Univ, Fac Med, Dept Med, Kuwait, Kuwait..
    Panagiotidis, Panagiotis
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Costeas, Paul
    Ctr Study Haematol Malignancies, Nicosia, Cyprus.;Karaiskakio Fdn, Nicosia, Cyprus..
    Espinet, Blanca
    Hosp Mar, Serv Patol & Serv Hematol, Lab Citogenet Mol, Lab Citol Hematol, Barcelona, Spain..
    Antic, Darko
    Clin Ctr Serbia, Clin Hematol, Belgrade, Serbia..
    Foroni, Letizia
    Hammersmith Hosp, London, England..
    Montillo, Marco
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Haematol Dept, Mol Pathol Unit, Milan, Italy..
    Trentin, Livio
    Univ Padua, Dept Med DIMED, Hematol & Clin Immunol Unit, Padua, Italy.;Veneto Inst Mol Med, Padua, Italy..
    Stavroyianni, Niki
    G Papanicolaou Hosp, Hematol Dept, Hematocrit HCT Unit, Thessaloniki, Greece..
    Gaidano, Gianluca
    Univ Eastern Piedmont Osped Maggiore Carita, Dept Translat Med, Div Hematol, Novara, Italy..
    di Celle, Paola Francia
    Azienda Osped Univ AOU, City Hlth & Sci Turin, Gen Anatomopathol & Mol Oncogenet, Turin, Italy..
    Niemann, Carsten
    Copenhagen Univ Hosp, Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Campo, Elias
    Ctr Invest Biomed Red Oncol CIBERONC, Madrid, Spain.;Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain.;Univ Barcelona, Hosp Clin Barcelona, Barcelona, Spain..
    Anagnostopoulos, Achilles
    Hammersmith Hosp, London, England..
    Pott, Christiane
    Univ Hosp Schleswig Holstein, Med Dept 2, Campus Kiel, Kiel, Germany..
    Fischer, Kirsten
    Univ Hosp Cologne, Cologne, Germany..
    Hallek, Michael
    Univ Cologne, Dept & Internal Med, Cologne, Germany..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Stilgenbauer, Stephan
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Haferlach, Claudia
    MLL Munich Leukemia Lab, Munich, Germany..
    Jelinek, Diane
    Mayo Clin, Dept Immunol, Scottsdale, AZ USA..
    Chiorazzi, Nicholas
    Feinstein Inst Med Res, Northwell Hlth, Manhasset, NY USA..
    Pospisilova, Sarka
    Masaryk Univ, Fac Med, Dept Internal Med Hematol & Oncol, Univ Hosp Brno, Brno, Czech Republic.;Masaryk Univ, Ctr Mol Med, Cent European Inst Technol, Brno, Czech Republic..
    Lefranc, Marie-Paule
    Univ Montpellier, Ctr Natl Rech Sci CNRS, Inst Genet Humaine IGH, Unite Mixte Rech UMR, Montpellier, France..
    Kossida, Sofia
    Univ Montpellier, Ctr Natl Rech Sci CNRS, Inst Genet Humaine IGH, Unite Mixte Rech UMR, Montpellier, France..
    Langerak, Anton W.
    Univ Med Ctr UMC, Dept Immunol, Lab Med Immunol, Erasmus MC, Rotterdam, Netherlands..
    Belessi, Chrysoula
    Nikea Gen Hosp, Hematol Dept, Piraeus, Greece..
    Davi, Frederic
    Univ Med Ctr UMC, Dept Immunol, Lab Med Immunol, Erasmus MC, Rotterdam, Netherlands..
    Rosenquist, Richard
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Karolinska Univ Lab, Clin Genet, Stockholm, Sweden..
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Strateg Res Program CLL,Ist Ricovero & Cura Carat, Milan, Italy..
    Stamatopoulos, Kostas
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL2021In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 137, no 10, p. 1365-1376Article in journal (Refereed)
    Abstract [en]

    Chronic lymphocytic leukemia (CLL) is characterized by the existence of subsets of patients with (quasi)identical, stereotyped B-cell receptor (BcR) immunoglobulins. Patients in certain major stereotyped subsets often display remarkably consistent clinicobiological profiles, suggesting that the study of BcR immunoglobulin stereotypy in CLL has important implications for understanding disease pathophysiology and refining clinical decision-making. Nevertheless, several issues remain open, especially pertaining to the actual frequency of BcR immunoglobulin stereotypy and major subsets, as well as the existence of higher-order connections between individual subsets. To address these issues, we investigated clonotypic IGHV-IGHD-IGHJ gene rearrangements in a series of 29 856 patients with CLL, by far the largest series worldwide. We report that the stereotyped fraction of CLL peaks at 41% of the entire cohort and that all 19 previously identified major subsets retained their relative size and ranking, while 10 new ones emerged; overall, major stereotyped subsets had a cumulative frequency of 13.5%. Higher-level relationships were evident between subsets, particularly for major stereotyped subsets with unmutated IGHV genes (U-CLL), for which close relations with other subsets, termed "satellites," were identified. Satellite subsets accounted for 3% of the entire cohort. These results confirm our previous notion that major subsets can be robustly identified and are consistent in relative size, hence representing distinct disease variants amenable to compartmentalized research with the potential of overcoming the pronounced heterogeneity of CLL. Furthermore, the existence of satellite subsets reveals a novel aspect of repertoire restriction with implications for refined molecular classification of CLL.

  • 20.
    Agathangelidis, Andreas
    et al.
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Ljungström, Viktor
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Scarfo, Lydia
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Fazi, Claudia
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Gounari, Maria
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy;Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Pandzic, Tatjana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Stamatopoulos, Kostas
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Tonon, Giovanni
    IRCCS Ist Sci San Raffaele, Funct Genom Canc Unit, Div Expt Oncol, Milan, Italy.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Highly similar genomic landscapes in monoclonal B-cell lymphocytosis and ultra-stable chronic lymphocytic leukemia with low frequency of driver mutations2018In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 103, no 5, p. 865-873Article in journal (Refereed)
    Abstract [en]

    Despite the recent discovery of recurrent driver mutations in chronic lymphocytic leukemia, the genetic factors involved in disease onset remain largely unknown. To address this issue, we per-formed whole-genome sequencing in 11 individuals with monoclonal B-cell lymphocytosis, both of the low-count and high-count subtypes, and 5 patients with ultra-stable chronic lymphocytic leukemia (>10 years without progression from initial diagnosis). All three entities were indistinguishable at the genomic level exhibiting low genomic complexity and similar types of somatic mutations. Exonic mutations were not frequently identified in putative chronic lymphocytic leukemia driver genes in all settings, including low-count monoclonal B-cell lymphocytosis. To corroborate these findings, we also performed deep sequencing in 11 known frequently mutated genes in an extended cohort of 28 monoclonal B-cell lym phocytosis/chronic lymphocytic leukemia cases. Interestingly, shared mutations were detected between clonal B cells and paired polymorphonuclear cells, strengthening the notion that at least a fraction of somatic mutations may occur before disease onset, likely at the hematopoietic stem cell level. Finally, we identified previously unreported non-coding variants targeting pathways relevant to B-cell and chronic lymphocytic leukemia development, likely associated with the acquisition of the characteristic neoplastic phenotype typical of both monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia.

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  • 21. Agathangelidis, Andreas
    et al.
    Vardi, Anna
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Stereotyped B-cell receptors in chronic lymphocytic leukemia2014In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 55, no 10, p. 2252-2261Article, review/survey (Refereed)
    Abstract [en]

    Over the last decade, immunogenetic analysis of B-cell receptor immunoglobulins (BcR IGs) has proved to be a particularly fruitful field in chronic lymphocytic leukemia (CLL), not only for understanding disease pathogenesis but also for discriminating clinical subgroups with markedly distinct course and outcome. Of utmost importance was the identification of quasi-identical BcR IGs among unrelated patients with CLL, fittingly coined as "stereotypy," that set the wheels in motion for unraveling the role of antigen(s) in the selection and expansion of the leukemic clones. The categorization of CLL clones into "subsets" according to shared BcR IG structural characteristics provided a compartmentalized view of this otherwise heterogeneous disease, which eventually led to defining strikingly homogeneous groups of patients in terms of: (i) functional properties of the clonal BcR IGs, e. g. BcR reactivity and signaling; (ii) clonal genetic landscape, e. g. genomic aberrations, gene expression/methylation profiles, microRNA signatures; and (iii) clinical course and outcome. The remarkable restriction of the CLL IG gene repertoire, resulting to a great degree from the high impact of BcR IG stereotypy, may also prompt speculations regarding CLL ontogenesis. Overall, the BcR IG molecule justifiably lies at the heart of CLL clinical research, holding the promise of subset-tailored therapies.

  • 22.
    Ahacic, Kozma
    et al.
    Karolinska Institutet.
    Kåreholt, Ingemar
    Jönköping University, School of Health and Welfare, HHJ. Ageing - living conditions and health. Jönköping University, School of Health and Welfare, HHJ, Institute of Gerontology.
    Helgason, Asgeir R
    Karolinska Institutet.
    Allebeck, Peter
    Karolinska Institutet.
    Non-response bias and hazardous alcohol use in relation to previous alcohol-related hospitalization: comparing survey responses with population data2013In: Substance Abuse Treatment, Prevention, and Policy, E-ISSN 1747-597X, Vol. 8, no 10Article in journal (Refereed)
    Abstract [en]

    Background: This study examines whether alcohol-related hospitalization predicts survey non-response, and evaluates whether this missing data result in biased estimates of the prevalence of hazardous alcohol use and abstinence.

    Methods: Registry data on alcohol-related hospitalizations during the preceding ten years were linked to two representative surveys. Population data corresponding to the surveys were derived from the Stockholm County registry. The alcohol-related hospitalization rates for survey responders were compared with the population data, and corresponding rates for non-responders were based on the differences between the two estimates. The proportions with hazardous alcohol use and abstinence were calculated separately for previously hospitalized and non-hospitalized responders, and non-responders were assumed to be similar to responders in this respect.

    Results: Persons with previous alcohol-related admissions were more likely currently to abstain from alcohol (RR=1.58, p<.001) or to have hazardous alcohol use (RR=2.06, p<.001). Alternatively, they were more than twice as likely to have become non-responders. Adjusting for this skewed non-response, i.e., the underrepresentation of hazardous users and abstainers among the hospitalized, made little difference to the estimated rates of hazardous use and abstinence in total. During the ten-year period 1.7% of the population were hospitalized.

    Conclusions: Few people receive alcohol-related hospital care and it remains unclear whether this group’s underrepresentation in surveys is generalizable to other groups, such as hazardous users. While people with severe alcohol problems – i.e. a history of alcohol-related hospitalizations – are less likely to respond to population surveys, this particular bias is not likely to alter prevalence estimates of hazardous use.

  • 23.
    Ahlner Elmqvist, Marianne
    et al.
    Malmö högskola, Faculty of Health and Society (HS).
    Jordhøy, Marit S
    Bjordal, Kristin
    Jannert, Magnus
    Kaasa, Stein
    Characteristics and Quality of Life of Patients Who Choose Home Care at the End of Life2008In: Journal of Pain and Symptom Management, ISSN 0885-3924, E-ISSN 1873-6513, Vol. 36, no 3, p. 217-227Article in journal (Refereed)
    Abstract [en]

    Cancer patients with advanced disease and short-survival expectancy were given hospitalbased advanced home care (AHC) or conventional care (CC), according to their preference. The two groups were compared at baseline to investigate whether there were differences between the AHC and the CC patients that may help explain their choice of care. The patients were consecutively recruited over 2½ years. Sociodemographic and medical data, and the health-related quality of life (HRQL) of the two groups were compared. HRQL was assessed using a self-reporting questionnaire, including the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQC30), the Impact of Event Scale (IES), five questions about social support, and two items concerning general well-being. The AHC group showed significantly poorer functioning on all the EORTC QLQ-C30 scales and an overall higher symptom burden than the CC patients. Fewer of the AHC patients were receiving cancer treatment. The AHC patients had lived longer with their cancer diagnosis, had a significantly shorter survival after study enrollment, and a significantly poorer performance status. The major differences between the two groups seemed to be related to being at different stages in their disease. The results indicate that patients are reluctant to accept home care until absolutely necessary due to severity of functioning impairments and symptom burden. These findings should be taken into consideration in planning palliative care services. J Pain Symptom Manage 2008;36:217e227. 2008 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  • 24.
    Ahlstrand, Erik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Coagulase-negative staphylococci in hematological malignancy2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Bacterial infections are common in hematological malignancy. Coagulase-negative staphylococci (CoNS) are among the most prevalent causes of bacteremia in patients with hematological malignancies.

    In this thesis, different aspects of CoNS in hematological malignancy have been studied in four papers:

    In paper 1, CoNS blood culture isolates from patients with hematological malignancies treated at the University Hospital of Örebro from 1980 to 2009 were revaluated for the presence of reduced sensitivity to glycopeptides. A high incidence of heterogeneous-intermediate glycopeptide resistance was observed and there was a trend towards increasing incidence of this phenotype over time.

    In paper 2, the colonization pattern of CoNS among patients undergoing intensive chemotherapy for hematological malignancy was investigated. A successive homogenization and an accumulation of CoNS phenotypes mutually present in a majority of included patients were demonstrated.

    In paper 3, a PCR method to determine the clinical significance of positive blood cultures of the CoNS species Staphylococcus epidermidis was evaluated. The test failed to discriminate bloodstream infection from blood culture contamination.

    Finally, in paper 4, the long-term molecular epidemiology of S. epidermidis blood culture isolates from patients with hematological malignancies was studied with multilocus sequence typing. A predominance of sequence type 2 was demonstrated during the entire 30 year study period.

    In conclusion, the results are consistent with that CoNS have established as important pathogens by its capacity to colonize the human skin, its ability to reside and spread in the hospital environment and its rapid adaptation to stressors such as antimicrobials.

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  • 25.
    Ahlstrand, Erik
    et al.
    Orebro Univ, Sweden.
    Samuelsson, Jan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Lindgren, Marie
    Kalmar Cty Hosp, Sweden.
    Pettersson, Helna
    NU Hosp Grp, Sweden.
    Liljeholm, Maria
    Univ Hosp Nouthern Sweden, Sweden.
    Ravn-Landtblom, Anna
    Karolinska Inst, Sweden; Stockholm South Hosp, Sweden.
    Scheding, Stefan
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Andreasson, Bjorn
    NU Hosp Grp, Sweden.
    Highly reduced survival in essential thrombocythemia and polycythemia vera patients with vascular complications during follow-up2020In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 104, no 3, p. 271-278Article in journal (Refereed)
    Abstract [en]

    Objective To explore the relative importance of risk factors, treatments, and blood counts for the occurrence of vascular complications and their impact on life expectancy in essential thrombocythemia (ET) and polycythemia vera (PV). Methods Nested case-control study within the Swedish MPN registry. From a cohort of 922 ET patients and 763 PV patients, 71 ET and 81 PV cases with vascular complications were compared with matched controls. Results Incidence of vascular complications was 2.0 and 3.4 events per 100 patient-years in ET and PV, respectively. At diagnosis, no significant risk factor differences were observed between cases and controls in neither of the diseases. At the time of vascular event, ET complication cases did not differ significantly from controls but in PV, cases had significantly higher WBCs and were to a lesser extent treated with anti-thrombotic and cytoreductive therapy. Life expectancy was significantly decreased in both ET and PV cases compared with controls. Conclusions The risk of vascular complications is high in both ET and PV, and these complications have a considerable impact on life expectancy. The protective effect of anti-thrombotic and cytoreductive therapy for vascular complications in PV underscores the importance of avoiding undertreatment.

  • 26.
    Ahlstrand, Erik
    et al.
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Medicine.
    Samuelsson, Jan
    Department of Hematology, University Hospital Linköping, Linköping, Sweden.
    Lindgren, Marie
    Department of Medicine, Kalmar County Hospital, Sweden.
    Pettersson, Helna
    Division of Hematology, Specialist Medicine, NU Hospital Group, Uddevalla, Sweden.
    Liljeholm, Maria
    Department of Hematology, University Hospital of Northern Sweden, Umeå, Sweden.
    Ravn-Landtblom, Anna
    Department of Medicine, Karolinska Institute, Department of Medicine, Division of Hematology, Stockholm South Hospital, Stockholm, Sweden.
    Scheding, Stefan
    Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Lund University, Lund, Sweden; Department of Hematology, Skåne University Hospital, Lund, Sweden.
    Andréasson, Björn
    Division of Hematology, Specialist Medicine, NU Hospital Group, Uddevalla, Sweden.
    Highly Reduced Survival in Essential Thrombocythemia and Polycythemia Vera Patients with Vascular Complications during Follow-up2020In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 104, no 3, p. 271-278Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To explore the relative importance of risk factors, treatments and blood counts for the occurrence of vascular complications and their impact on life expectancy in Essential Thrombocythemia (ET) and Polycythemia Vera (PV).

    METHODS: Nested case-control study within the Swedish MPN registry. From a cohort of 922 ET patients and 763 PV patients, 71 ET and 81 PV cases with vascular complications were compared to matched controls.

    RESULTS: Incidence of vascular complications were 2.0 and 3.4 events per 100 patient-years in ET and PV, respectively. At diagnosis, no significant risk factor differences were observed between cases and controls in neither of the diseases. At the time of vascular event, ET complication cases did not differ significantly from controls but in PV, cases had significantly higher WBCs and were to a lesser extent treated with antithrombotic and cytoreductive therapy. Life expectancy was significantly decreased in both ET and PV cases compared to controls.

    CONCLUSIONS: The risk of vascular complications is high in both ET and PV and these complications have a considerable impact on life expectancy. The protective effect of antithrombotic and cytoreductive therapy for vascular complications in PV underscores the importance of avoiding undertreatment.

  • 27.
    Ahmed, Sairah
    et al.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA..
    Ghosh, Nilanjan
    Atrium Hlth, Levine Canc Inst, Hematol Oncol & Blood Disorders, Charlotte, NC USA..
    Ahn, Kwang W.
    Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA.;Med Coll Wisconsin, Inst Hlth & Equ, Div Biostat, Milwaukee, WI 53226 USA..
    Khanal, Manoj
    Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA..
    Litovich, Carlos
    Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA..
    Mussetti, Alberto
    Inst Catal Oncol Hosp, Hematol Dept, Barcelona, Spain.;Hosp Llobregat, IDIBELL Inst Catala Oncol, El Prat De Llobregat, Spain..
    Chhabra, Saurabh
    Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA.;Med Coll Wisconsin, Dept Med, Div Hematol & Oncol, Milwaukee, WI 53226 USA..
    Cairo, Mitchell
    New York Med Coll, Dept Pediat, Div Pediat Hematol Oncol & Stem Cell Transplantat, Valhalla, NY 10595 USA..
    Mei, Matthew
    City Hope Natl Med Ctr, Duarte, CA USA..
    William, Basem
    Ohio State Univ, Div Hematol, Columbus, OH 43210 USA..
    Nathan, Sunita
    Rush Univ, Med Ctr, Chicago, IL 60612 USA..
    Bejanyan, Nelli
    H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplant & Cellular Immunot, Tampa, FL USA..
    Olsson, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Dept Lab Med, Stockholm, Sweden..
    Dahi, Parastoo B.
    Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplant Serv, 1275 York Ave, New York, NY 10021 USA..
    van der Poel, Marjolein
    Maastricht Univ, Med Ctr, Maastricht, Netherlands..
    Steinberg, Amir
    Mt Sinai Hosp, Div Hematol & Oncol, New York, NY 10029 USA..
    Kanakry, Jennifer
    NCI, NIH, Bethesda, MD 20892 USA..
    Cerny, Jan
    Univ Massachusetts, Med Ctr, Dept Med, Div Hematol Oncol, Worcester, MA USA..
    Farooq, Umar
    Univ Iowa Hosp & Clin, Div Hematol, Oncol & Blood & Marrow Transplantat, Iowa City, IA 52242 USA..
    Seo, Sachiko
    Dokkyo Med Univ, Dept Hematol & Oncol, Mibu, Tochigi, Japan..
    Kharfan-Dabaja, Mohamed A.
    Mayo Clin, Div Hematol Oncol, Blood & Marrow Transplantat Program, Jacksonville, FL 32224 USA..
    Sureda, Anna
    Univ Barcelona, Inst Catal Oncol Hosp, Hematol Dept, IDIBELL, Barcelona, Spain..
    Fenske, Timothy S.
    Med Coll Wisconsin, Dept Med, Div Hematol & Oncol, Milwaukee, WI 53226 USA..
    Hamadani, Mehdi
    Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA.;Med Coll Wisconsin, Dept Med, Div Hematol & Oncol, Milwaukee, WI 53226 USA..
    Impact of type of reduced-intensity conditioning regimen on the outcomes of allogeneic haematopoietic cell transplantation in classical Hodgkin lymphoma2020In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 190, no 4, p. 573-582Article in journal (Refereed)
    Abstract [en]

    Reduced-intensity conditioning (RIC) allogeneic haematopoietic cell transplantation (allo-HCT) is a curative option for select relapsed/refractory Hodgkin lymphoma (HL) patients; however, there are sparse data to support superiority of any particular conditioning regimen. We analyzed 492 adult patients undergoing human leucocyte antigen (HLA)-matched sibling or unrelated donor allo-HCT for HL between 2008 and 2016, utilizing RIC with either fludarabine/busulfan (Flu/Bu), fludarabine/melphalan (Flu/Mel140) or fludarabine/cyclophosphamide (Flu/Cy). Multivariable regression analysis was performed using a significance level of <0 center dot 01. There were no significant differences between regimens in risk for non-relapse mortality (NRM) (P = 0 center dot 54), relapse/progression (P = 0 center dot 02) or progression-free survival (PFS) (P = 0 center dot 14). Flu/Cy conditioning was associated with decreased risk of mortality in the first 11 months after allo-HCT (HR = 0 center dot 28; 95% CI = 0 center dot 10-0 center dot 73; P = 0 center dot 009), but beyond 11 months post allo-HCT it was associated with a significantly higher risk of mortality, (HR = 2 center dot 46; 95% CI = 0 center dot 1.32-4 center dot 61; P = 0 center dot 005). Four-year adjusted overall survival (OS) was similar across regimens at 62% for Flu/Bu, 59% for Flu/Mel140 and 55% for Flu/Cy (P = 0 center dot 64), respectively. These data confirm the choice of RIC for allo-HCT in HL does not influence risk of relapse, NRM or PFS. Although no OS benefit was seen between Flu/Bu and Flu/Mel 140; Flu/Cy was associated with a significantly higher risk of mortality beyond 11 months from allo-HCT (possibly due to late NRM events).

  • 28.
    Akram, Talia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE-C)-PIEAS, Faisalabad, Pakistan.
    Fatima, Ambrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Klar, Joakim
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Hoeber, Jan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Zakaria, Muhammad
    Tariq, Muhammad
    Baig, Shahid M.
    Schuster, Jens
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Dahl, Niklas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Aberrant splicing due to a novel RPS7 variant causes Diamond-Blackfan Anemia associated with spontaneous remission and meningocele2020In: International Journal of Hematology, ISSN 0925-5710, E-ISSN 1865-3774, Vol. 112, no 6, p. 894-899Article in journal (Refereed)
    Abstract [en]

    Diamond-Blackfan Anemia (DBA) is a congenital pure red cell aplasia caused by heterozygous variants in ribosomal protein genes. The hematological features associated with DBA are highly variable and non-hematological abnormalities are common. We report herein on an affected mother and her daughter presenting with transfusion-dependent anemia. The mother showed mild physical abnormalities and entered spontaneous remission at age 13 years. Her daughter was born with occipital meningocele. Exome sequencing of DNA from the mother revealed a heterozygous novel splice site variant (NM_001011.4:c.508-3T > G) in the Ribosomal Protein S7 gene (RPS7) inherited by the daughter. Functional analysis of the RPS7 variant expressed from a mini-gene construct revealed that the exon 7 acceptor splice site was replaced by a cryptic splice resulting in a transcript missing 64 bp of exon 7 (p.Val170Serfs*8). Our study confirms a pathogenic effect of a novel RPS7 variant in DBA associated with spontaneous remission in the mother and meningocele in her daughter, thus adding to the genotype-phenotype correlations in DBA.

  • 29.
    Albertsson-Lindblad, Alexandra
    et al.
    Skane Univ Hosp, Dept Oncol, SE-22185 Lund, Sweden..
    Kolstad, Arne
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway..
    Laurell, Anna
    Univ Uppsala Hosp, Dept Oncol, Uppsala, Sweden..
    Raty, Riikka
    Helsinki Univ Hosp, Dept Hematol, Helsinki, Finland..
    Gronbaek, Kirsten
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Sundberg, Jan
    Skane Univ Hosp, Dept Oncol, SE-22185 Lund, Sweden..
    Pedersen, Lone Bredo
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Ralfkiaer, Elisabeth
    Rigshosp, Dept Pathol, Copenhagen, Denmark..
    Karjalainen-Lindsberg, Marja-Liisa
    Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland..
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Department of Pathology, Uppsala University Hospital, Uppsala, Sweden; and..
    Ehinger, Mats
    Univ Lund Hosp, Dept Pathol Cytol, Lund, Sweden..
    Geisler, Christian
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Jerkeman, Mats
    Skane Univ Hosp, Dept Oncol, SE-22185 Lund, Sweden..
    Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma2016In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 128, no 14, p. 1814-1820Article in journal (Refereed)
    Abstract [en]

    For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter, open-label phase 1/2 trial, we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment for elderly patients with MCL. Patients >65 years with untreated MCL, stages II-IV were eligible for inclusion. Primary end points were maximally tolerable dose (MTD) of LEN and progression-free survival (PFS). Patients received 6 cycles every four weeks of L-B-R (L D1-14, B 90 mg/m(2) IV, days 1-2 and R 375 mg/m(2) IV, day 1) followed by single LEN (days 1-21, every four weeks, cycles 7-13). Fifty-one patients (median age 71 years) were enrolled from 2009 to 2013. In phase 1, the MTD of LEN was defined as 10 mg in cycles 2 through 6, and omitted in cycle 1. After 6 cycles, the complete remission rate (CRR) was 64%, and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3-year overall survival was 73%. Infection was the most common nonhematologic grade 3 to 5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in 3 patients: 2 Pneumocystis carinii pneumonia and 1 cytomegalovirus retinitis. Second primary malignancies (SPM) were observed in 8 patients (16%). LEN could safely be combined with R-B when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs, which may limit its use. This trial is registered at www.Clinicaltrials.gov as #NCT00963534.

  • 30.
    Albertsson-Lindblad, Alexandra
    et al.
    Lund Univ, Skane Univ Hosp, Div Oncol, Lund, Sweden..
    Palsdottir, Thorgerdur
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Smedby, Karin E.
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Univ Hosp, Div Hematol, Dept Med Solna, Stockholm, Sweden..
    Weibull, Caroline E.
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Glimelius, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Uppsala Akad Hosp, Uppsala, Sweden..
    Jerkeman, Mats
    Lund Univ, Skane Univ Hosp, Div Oncol, Lund, Sweden..
    Survival in mantle cell lymphoma after frontline treatment with R-bendamustine, R-CHOP and the Nordic MCL2 regimen - a real world study on patients diagnosed in Sweden 2007-20172022In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 107, no 3, p. 740-743Article in journal (Other academic)
  • 31.
    Ali Abdi, Abshir
    et al.
    East Africa University, Somalia.
    Osman, Abdimajid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Prevalence of common hereditary risk factors for thrombophilia in Somalia and identification of a novel Gln544Arg mutation in coagulation factor V2017In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 44, no 4, p. 536-543Article in journal (Refereed)
    Abstract [en]

    Thrombophilia, commonly manifested as venous thromboembolism (VTE), is a worldwide concern but little is known on its genetic epidemiology in many parts of the globe particularly in the developing countries. Here we employed TaqMan genotyping and pyrosequencing to evaluate the prevalence of known common nucleotide polymorphisms associated with thrombophilia in a Somali population in the Puntland region of Somalia. We also employed next generation sequencing (NGS) to investigate other genetic variants in a Somali patient with deep venous thrombosis (DVT). As expected, we found no existence of factor V Leiden (rs6025) and prothrombin G20210A (rs1799963) in the Somali population. The G allele of ABO [261G/delG] polymorphism (rs8176719) was found at a frequency of 29%, similar to that observed in other African populations. We found the lowest so far reported frequency of MTHFR C677T (rs1801133) polymorphism in the Somali population (T allele frequency 1.5%). A novel and deleterious single nucleotide variation in exon 11 of coagulation factor V (c.1631A amp;gt; G) causing Gln544Arg exchange in factor V was identified in a 29 years old Somali female with DVT. The same patient was heterozygous to VKORC1 Asp36Tyr polymorphism (rs61742245) that predisposes to warfarin resistance. In conclusion, this study shows that common hereditary factors for thromboembolism found in Caucasians are either less frequent or absent in the Somali population-similar to the situation in other Africans. NGS is possibly a better choice to detect genetic risk variants for thrombosis in this ethnic group.

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  • 32.
    Ali, Dina
    et al.
    Karolinska Univ Hosp, Haematol Ctr, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Haematol & Regenerat Med HERM, Stockholm, Sweden..
    Mohammad, Dara K.
    Karolinska Inst, Karolinska Hosp Huddinge, Clin Res Ctr, Dept Lab Med, Stockholm, Sweden..
    Mujahed, Huthayfa
    Karolinska Univ Hosp, Haematol Ctr, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Haematol & Regenerat Med HERM, Stockholm, Sweden..
    Jonson-Videsater, Kerstin
    Karolinska Univ Hosp, Dept Clin Immunol, Stockholm, Sweden..
    Nore, Beston
    Karolinska Inst, Karolinska Hosp Huddinge, Clin Res Ctr, Dept Lab Med, Stockholm, Sweden..
    Paul, Christer
    Karolinska Univ Hosp, Haematol Ctr, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Haematol & Regenerat Med HERM, Stockholm, Sweden..
    Lehmann, Sören
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Karolinska Univ Hosp, Haematol Ctr, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Haematol & Regenerat Med HERM, Stockholm, Sweden..
    Anti-leukaemic effects induced by APR-246 are dependent on induction of oxidative stress and the NFE2L2/HMOX1 axis that can be targeted by PI3K and mTOR inhibitors in acute myeloid leukaemia cells2016In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 174, no 1, p. 117-126Article in journal (Refereed)
    Abstract [en]

    The small molecule APR-246 (PRIMA-1(MET)) is a novel drug that restores the activity of mutated and unfolded TP53 protein. However, the mechanisms of action and potential off-target effects are not fully understood. Gene expression profiling in TP53 mutant KMB3 acute myeloid leukaemia (AML) cells showed that genes which protected cells from oxidative stress to be the most up-regulated. APR-246 exposure also induced reactive oxygen species (ROS) formation and depleted glutathione in AML cells. The genes most up-regulated by APR-246, confirmed by quantitative real time polymerase chain reaction, were heme oxygenase-1 (HMOX1, also termed HO-1), SLC7A11 and RIT1. Up-regulation of HMOX1, a key regulator of cellular response to ROS, was independent of TP53 mutational status. NFE2L2 (also termed Nrf2), a master regulator of HMOX1 expression, showed transcriptional up-regulation and nuclear translocation by APR-246. Down-regulation of NFE2L2 by siRNA in AML cells significantly increased the antitumoural effects of APR-246. The PI3K inhibitor wortmannin and the mTOR inhibitor rapamycin inhibited APR-246-induced nuclear translocation of NFE2L2 and counteracted the protective cellular responses to APR-246, resulting in synergistic cell killing together with APR-246. In conclusion, ROS induction is important for antileukaemic activities of APR-246 and inhibiting the protective response of the Nrf-2/HMOX1 axis using PI3K inhibitors, enhances the antileukaemic effects.

  • 33.
    Ali, M. M.
    et al.
    Oslo Univ Hosp, Dept Haematol, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Gronvold, B.
    Oslo Univ Hosp, Dept Haematol, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Remberger, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Oslo Univ Hosp, Dept Haematol, Oslo, Norway.; Uppsala Univ Hosp, KFUE, Uppsala, Sweden..
    Abrahamsen, I. W.
    Oslo Univ Hosp, Dept Haematol, Oslo, Norway..
    Myhre, A. E.
    Oslo Univ Hosp, Dept Haematol, Oslo, Norway..
    Tjonnfjord, G. E.
    Oslo Univ Hosp, Dept Haematol, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Floisand, Y.
    Univ Oslo, Inst Clin Med, Ctr Canc Cell Reprogramming, Oslo, Norway.;Clatterbridge Canc Ctr NHS Fdn Trust, Liverpool, Merseyside, England..
    Gedde-Dahl, T.
    Oslo Univ Hosp, Dept Haematol, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Addition of Anti-thymocyte Globulin in Allogeneic Stem Cell Transplantation With Peripheral Stem Cells From Matched Unrelated Donors Improves Graft-Versus-Host Disease and Relapse Free Survival2021In: Clinical Lymphoma, Myeloma & Leukemia, ISSN 2152-2650, E-ISSN 2152-2669, Vol. 21, no 9, p. 598-605Article in journal (Refereed)
    Abstract [en]

    In 2014 we introduced anti-thymocyte globulin (ATG) to the graft-versus-host disease (GvHD) prophylaxis regimen in allogeneic stem cell transplantation (Allo-HSCT) with peripheral stem cells (PBSC) from matched unrelated donors (MUD). We analysed the outcomes of 415 patients who went through MUD alto-HSCT and received PBSC with or without ATG. We report dramatic reduction of the incidence of chronic GvHD and our study illustrates the benefit of ATG in addition to standard GvHD prophylaxis. Anti-thymocyte globulin (ATG) is commonly used to prevent graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). To evaluate the impact of ATG as part of the GvHD prophylaxis in our institution, we report the outcome of 415 patients with matched unrelated donors (MUD) transplanted for hemato-logical malignancies with or without ATG from 2005 to 2019 at Oslo University Hospital, Norway. The following groups were compared: (1) 154 patients transplanted with peripheral blood stem cells (PBSC) without ATG 2005-2014. (2) 137 patients transplanted with bone marrow stem cells (BMSC) 2005-2019. (3) 124 patients transplanted with PBSC and ATG (PBSC + ATG) 2014-2019. Three years survival was similar in the groups, 61% following allografting with PBSC, 54% with BMSC, and 59% with PBSC + ATG. Acute GvHD grade III-IV was 14%, 14%, and 7%; chronic GvHD was 81%, 32, and 26%; and extensive cGvHD 44%, 15%, and 6% in the corresponding groups. Both acute and chronic GvHD were significantly reduced in the PBSC + ATG-versus the PBSC group (p < 0.05 and p < 0.001 respectively).Transplant-related mortality (TRM) was 33%, 25%, and 17% (p = 0.18). Graft versus host disease and relapse free survival (GRFS) at 3 years was 43 %, 43%, and 64% in the groups. Adding ATG to the GvHD prophylaxis regimen of MUD allo-HSCT with PBSC resulted in a substantial reduction of both acute and chronic GvHD without compromising the disease control, reflected in a superior 3 years GRFS.

  • 34. Almgren, J.
    et al.
    Lindvall, P.
    Englund,
    Norda, Rut
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lubenow, Norbert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Safwenberg, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Comparison of Three Fully Automated Systems for Immunohematology with the Focus on Two Important Aspects of Capacity-Efficiency and Stress2014In: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 54, p. 173A-174AArticle in journal (Other academic)
  • 35.
    Alvarez-Larran, Alberto
    et al.
    Inst Invest Biomed August Pi & Sunyer IDIBAP, Hosp Clin, Hematol Dept, Barcelona, Spain..
    Sant'Antonio, Emanuela
    Univ Hosp Paolo Giaccone, Hematol Div, Palermo, Italy..
    Harrison, Claire
    Guys & StThomasNHS Fdn Trust, Dept Haematol, London, England..
    Kiladjian, Jean-Jacques
    Univ Paris, Ctr Invest Clin, Hop St Louis, AP HP,INSERM,CIC1427, Paris, France..
    Griesshammer, Martin
    Univ Bochum, Johannes Westing Med Ctr Minden UKRUB, Oncol Hemostaseol & Palliat Care, Bochum, Germany..
    Mesa, Ruben
    UT Hlth San Antonio MD Anderson, Mays Canc Ctr, San Antonio, TX USA..
    Ianotto, Jean Christophe
    CHRU Brest, Serv Hematol Clin, Inst Cancerol Hematol, Brest, France..
    Palandri, Francesca
    Univ Bologna, Ist Ematol Seragnor, IRCCS Azienda Osped, Bologna, Italy..
    Hernandez-Boluda, Juan Carlos
    Hosp Clin Valencia, Hematol Dept, Valencia, Spain..
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Nangalia, Jyoti
    Wellcome Sanger Inst, Cambridge, England..
    Koschmieder, Steffen
    Rhein Westfal TH Aachen, Fac Med, Dept Hematol Oncol Hemostaseol & Stem Cell Transp, Aachen, Germany..
    Rumi, Elisa
    Univ Pavia, Dept Mol Med, Pavia, Italy..
    Barbui, Tiziano
    Res Fdn Papa Giovanni XXIII Hosp, I-24127 Bergamo, Italy..
    Unmet clinical needs in the management of CALR-mutated essential thrombocythaemia: a consensus-based proposal from the European LeukemiaNet2021In: The Lancet Haematology, E-ISSN 2352-3026, Vol. 8, no 9, p. E658-E665Article, review/survey (Refereed)
    Abstract [en]

    Recommendations regarding management of essential thrombocythaemia rely on studies done before the discovery of the CALR mutation. On May 20, 2020, the European LeukemiaNet annual meeting was held with the goal to identify unmet clinical needs in myeloproliferative neoplasms. Because patients with a CALR mutation have specific clinical characteristics, treatment of CALR-mutated essential thrombocythaemia was considered an unmet clinical need by the European LeukemiaNet. The elaboration of a consensus document with recommendations according to current evidence was proposed as a solution for resolving uncertainties in the treatment of CALR-mutated essential thrombocythaemia. A steering committee comprising four European LeukemiaNet members was then formed and a panel of ten experts in the field was recruited. The experts proposed 51 potential unmet clinical needs in the management of CALR-mutated essential thrombocythaemia and were asked to score the relevance of each topic. Those topics that obtained the highest scores as relevant unmet clinical needs were identified, including antiplatelet therapy in patients at low risk, definition of extreme thrombocytosis and its management in patients at low risk, indications of cytoreduction and targets of therapy, first-line treatment of choice in young patients (<60 years), and management of pregnancy. After the steering committee revised the available evidence for each topic, a consensus on management and proposal for improving knowledge was achieved by use of an email-based, two round, Delphi approach. Consensus was achieved when 90% of the panellists agreed with a statement and included 14 recommendations and six solution proposals. Key recommendations included careful observation for asymptomatic patients with classical, low-risk, CALR-mutated essential thrombocythaemia without cardiovascular risk factors; caution in the use of antiplatelet therapy for symptomatic patients at low risk with platelet counts of 1000-1500 × 109 platelets per L, in such cases cytoreduction is an adequate option, especially if adquired Von Willebrand disease is present; cytoreduction is recommended for extreme thrombocytosis (platelet count >1500 × 109 platelets per L) with pegylated interferon alfa being the preferred option for younger patients; both hydroxycarbamide and anagrelide might be given to patients ineligible for pegylated interferon alfa; and treatment algorithms for patients with high-risk pregnancies should not be changed according to genotype. The European LeukemiaNet proposes to use these recommendations in the routine management of patients with CALR-mutated essential thrombocythaemia, and designing new clinical studies in this field might be useful. 

  • 36.
    Amarasinghe, H.
    et al.
    Univ Southampton, Acad Unit Canc Sci, Southampton, Hants, England..
    Wojdacz, T.
    Aarhus Univ, Aarhus Inst Adv Studies, Aarhus, Denmark..
    Rose-Zerilli, M.
    Univ Southampton, Acad Unit Canc Sci, Southampton, Hants, England..
    Beattie, A.
    Univ Southampton, Acad Unit Canc Sci, Southampton, Hants, England..
    Forster, J.
    Univ Southampton, Acad Unit Canc Sci, Southampton, Hants, England..
    Kadalayil, L.
    Univ Southampton, Genet Epidemiol & Bioinformat, Southampton, Hants, England..
    Blakemore, S.
    Univ Cologne, Dept Internal Med, Cologne, Germany..
    Parker, H.
    Univ Southampton, Acad Unit Canc Sci, Southampton, Hants, England..
    Larrayoz, M.
    Univ Navarra, Div Hematooncol, Pamplona, Spain..
    Clifford, R.
    Univ Oxford, Oxford Natl Inst Hlth Res, Biomed Res Ctr, Mol Diagnost Ctr, Oxford, England..
    Davis, Z.
    Royal Bournemouth Hosp, Dept Mol Pathol, Bournemouth, Dorset, England..
    Else, M.
    Inst Canc Res, Div Mol Pathol, London, England..
    Cohen, D.
    Univ Leeds, Leeds Inst Clin Trials Res, Leeds, W Yorkshire, England..
    Steele, A.
    Univ Southampton, Acad Unit Canc Sci, Southampton, Hants, England..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Collins, A.
    Univ Southampton, Human Dev & Hlth, Southampton, Hants, England..
    Pettitt, A.
    Univ Liverpool, Dept Mol & Clin Canc Med, Liverpool, Merseyside, England..
    Hillmen, P.
    St James Univ Hosp, Dept Haematol, Leeds, W Yorkshire, England..
    Plass, C.
    German Canc Res Ctr, Div Epigen & Canc Risk Factors, Heidelberg, Germany..
    Catovsky, D.
    Inst Canc Res, Div Mol Pathol, London, England..
    Schuh, A.
    Univ Oxford, Oxford Natl Inst Hlth Res, Biomed Res Ctr, Mol Diagnost Ctr, Oxford, England..
    Oscier, D.
    Royal Bournemouth Hosp, Dept Mol Pathol, Bournemouth, Dorset, England..
    Oakes, C.
    Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA..
    Strefford, J.
    Univ Southampton, Acad Unit Canc Sci, Southampton, Hants, England..
    Patients with a Memory-like DNA Methylation Signature exhibit long-term survival after first-line immuno-chemotherapy: Data from the UK CLL4, ARCTIC and ADMIRE trials2018In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 181, p. 29-29Article in journal (Other academic)
  • 37.
    Anastasopoulou, Stavroula
    et al.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Eriksson, Mats A.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Heyman, Mats
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Wang, Chen
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Niinimäki, Riitta
    Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland;Univ Oulu, PEDEGO Res Unit, Oulu, Finland.
    Mikkel, Sirje
    Univ Tartu, Dept Hematol & Oncol, Tartu, Estonia.
    Vaitkeviciene, Goda E.
    Vilnius Univ Hosp Santaros Klin, Childrens Hosp, Vilnius, Lithuania;Vilnius Univ, Vilnius, Lithuania.
    Johannsdottir, Inga Maria
    Oslo Univ Hosp, Dept Pediat Hematol Oncol, Oslo, Norway.
    Myrberg, Ida Hed
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Jonsson, Olafur Gisli
    Univ Iceland, Dept Pediat, Reykjavik, Iceland.
    Als-Nielsen, Bodil
    Rigshosp, Univ Hosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark;Univ Copenhagen, Fac Med, Inst Clin Med, Copenhagen, Denmark.
    Schmiegelow, Kjeld
    Rigshosp, Univ Hosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark;Univ Copenhagen, Fac Med, Inst Clin Med, Copenhagen, Denmark.
    Banerjee, Joanna
    Univ Helsinki, Childrens Hosp, Dept Pediat Hematol Oncol & Stem Cell Transplanta, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Harila-Saari, Arja H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Ranta, Susanna
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia: Clinical characteristics, risk factors, course, and outcome of disease2019In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 66, no 5, article id e27594Article in journal (Refereed)
    Abstract [en]

    Background: Posterior reversible encephalopathy syndrome (PRES) is a distinct entity with incompletely known predisposing factors. The aim of this study is to describe the incidence, risk factors, clinical course, and outcome of PRES in childhood acute lymphoblastic leukemia (ALL).

    Procedure: Patients aged 1.0 to 17.9 years diagnosed with ALL from July 2008 to December 2015 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol were included. Patients with PRES were identified in the prospective NOPHO leukemia toxicity registry, and clinical data were collected from the medical records.

    Results: The study group included 1378 patients, of whom 52 met the criteria for PRES. The cumulative incidence of PRES at one month was 1.7% (95% CI, 1.1-2.5) and at one year 3.7% (95% CI, 2.9-4.9). Older age (hazard ratios [HR] for each one-year increase in age 1.1; 95% CI, 1.0-1.2, P = 0.001) and T-cell immunophenotype (HR, 2.9; 95% CI, 1.6-5.3, P = 0.0005) were associated with PRES. Central nervous system (CNS) involvement (odds ratios [OR] = 2.8; 95% CI, 1.2-6.5, P = 0.015) was associated with early PRES and high-risk block treatment (HR = 2.63; 95% CI, 1.1-6.4, P = 0.033) with late PRES. At follow-up of the PRES patients, seven patients had epilepsy and seven had neurocognitive difficulties.

    Conclusion: PRES is a neurotoxicity in the treatment of childhood ALL with both acute and long-term morbidity. Older age, T-cell leukemia, CNS involvement and high-risk block treatment are risk factors for PRES.

  • 38.
    Anastasopoulou, Stavroula
    et al.
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden..
    Harila-Saari, Arja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatric oncological and neurological research.
    Als-Nielsen, Bodil
    Univ Hosp, Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark..
    Eriksson, Mats Anders
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Neuropediat Unit, Stockholm, Sweden..
    Heyman, Mats
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden..
    Johannsdottir, Inga Maria
    Oslo Univ Hosp, Dept Pediat Hematol Oncol, Oslo, Norway..
    Marquart, Hanne Vibeke
    Univ Copenhagen, Rigshosp, Dept Clin Immunol, Copenhagen, Denmark..
    Niinimäki, Riitta
    Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland.;Univ Oulu, PEDEGO Res Unit, Oulu, Finland..
    Pronk, Cornelis Jan
    Skane Univ Hosp, Childhood Canc Ctr, Lund, Sweden..
    Schmiegelow, Kjeld
    Univ Hosp, Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark.;Univ Copenhagen, Fac Med, Inst Clin Med, Copenhagen, Denmark..
    Vaitkeviciene, Goda
    Vilnius Univ, Hosp Santaros Klin, Childrens Hosp, Vilnius, Lithuania..
    Thastrup, Maria
    Univ Hosp, Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark..
    Ranta, Susanna
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden..
    Does minimal central nervous system involvement in childhood acute lymphoblastic leukemia increase the risk for central nervous system toxicity?2022In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 69, no 7, article id e29745Article in journal (Refereed)
    Abstract [en]

    Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) implicates enhanced intrathecal chemotherapy, which is related to CNS toxicity. Whether CNS involvement alone contributes to CNS toxicity remains unclear. We studied the occurrence of all CNS toxicities, seizures, and posterior reversible encephalopathy syndrome (PRES) in children with ALL without enhanced intrathecal chemotherapy with CNS involvement (n = 64) or without CNS involvement (n = 256) by flow cytometry. CNS involvement increased the risk for all CNS toxicities, seizures, and PRES in univariate analysis and, after adjusting for induction therapy, for seizures (hazard ratio [HR] = 3.33; 95% confidence interval [CI]: 1.26-8.82; p = 0.016) and PRES (HR = 4.85; 95% CI: 1.71-13.75; p = 0.003).

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  • 39.
    Anastasopoulou, Stavroula
    et al.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Heyman, Mats
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Eriksson, Mats A.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Niinimaki, Riitta
    Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland.;Univ Oulu, PEDEGO Res Unit, Oulu, Finland..
    Taskinen, Mervi
    Helsinki Univ Hosp, Div Pediat Hematol & Oncol & Stem Cell Transplant, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland..
    Mikkel, Sirje
    Univ Tartu, Dept Hematol & Oncol, Tartu, Estonia..
    Vaitkeviciene, Goda E.
    Vilnius Univ Hosp Santaros Klin, Childrens Hosp, Vilnius, Lithuania.;Vilnius Univ, Vilnius, Lithuania..
    Johannsdottir, Inga Maria
    Oslo Univ Hosp, Dept Pediat Hematol Oncol, Oslo, Norway..
    Myrberg, Ida Hed
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Jonsson, Olafur Gisli
    Univ Iceland, Dept Pediat, Reykjavik, Iceland..
    Als-Nielsen, Bodil
    Univ Copenhagen, Rigshosp, Dept Paediat & Adolescent Med, Copenhagen, Denmark..
    Schmiegelow, Kjeld
    Univ Copenhagen, Rigshosp, Dept Paediat & Adolescent Med, Copenhagen, Denmark.;Univ Copenhagen, Fac Med, Inst Clin Med, Copenhagen, Denmark..
    Banerjee, Joanna
    Helsinki Univ Hosp, Div Pediat Hematol & Oncol & Stem Cell Transplant, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland..
    Ranta, Susanna
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Harila-Saari, Arja H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Seizures during treatment of childhood acute lymphoblastic leukemia: A population-based cohort study2020In: European journal of paediatric neurology, ISSN 1090-3798, E-ISSN 1532-2130, Vol. 27, p. 72-77Article in journal (Refereed)
    Abstract [en]

    Background: Seizures are common in children with acute lymphoblastic leukemia (ALL). As ALL survival rates are improving, the challenge to minimize treatment related side effects and late sequelae rises. Here, we studied the frequency, timing, etiology and risk factors of seizures in ALL patients. Methods: The study included children aged 1-17.9 years at diagnosis of B-cell-precursor and T cell ALL who were treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol between 2008 and 2015. Detailed patient data were acquired from the NOPHO ALL2008 registry and by review of medical records. Results: Seizures occurred in 81/1464 (5.5%) patients. The cumulative incidence of seizures at one months was 1.7% (95% CI: 1.2-2.5) and at one year 5.3% (95% CI 4.2-6.5%). Patients aged 10-17.9 years, those with T cell immunophenotype, CNS involvement, or high-risk induction with dexamethasone had higher risk for seizures in univariable analyses. Only age remained a risk factor in multivariable analyses (the cumulative incidence of seizures for patients 10-17.9 years old at one year was 9.0% (95% CI: 6.2-12.9)). Of the 81 patients with seizures, 43 had posterior reversible encephalopathy syndrome (PRES), 15 had isolated seizures, nine had sinus venous thrombosis (SVT), three had stroke-like syndrome, and 11 had other neurotoxicities. Epilepsy diagnosis was reported in totally 11 ALL survivors at last follow up. Conclusion: Seizures are relatively common in ALL patients and occur most often in patients with PRES, SVT, or as an isolated symptom. Older children have higher risk of seizures. (C) 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  • 40.
    Anastasopoulou, Stavroula
    et al.
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden..
    Nielsen, Rikke Linnemann
    Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark.;Tech Univ Denmark, Dept Hlth Technol, Lyngby, Denmark.;Novo Nordisk Res Ctr Oxford, Oxford, Oxfordshire, England..
    Als-Nielsen, Bodil
    Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark..
    Banerjee, Joanna
    Univ Helsinki, Helsinki Univ Hosp, Div Pediat Hematol & Oncol & Stem Cell Transplanta, Helsinki, Finland..
    Eriksson, Mats A.
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Helenius, Marianne
    Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark.;Tech Univ Denmark, Dept Hlth Technol, Lyngby, Denmark..
    Heyman, Mats M.
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Neuropediat Unit, Stockholm, Sweden..
    Johannsdottir, Inga Maria
    Oslo Univ Hosp, Dept Pediat Hematol Oncol, Oslo, Norway..
    Jonsson, Olafur Gisli
    Landspitali Univ Hosp, Dept Pediat, Reykjavik, Iceland..
    MacGregor, Stuart
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Mateos, Marion K.
    Sydney Childrens Hosp Randwick, Kids Canc Ctr, Sydney, NSW, Australia.;Univ New South Wales, Sch Clin Med, Discipline Paediat & Child Hlth, Sydney, NSW, Australia.;Univ New South Wales, Childrens Canc Inst, Lowy Canc Res Ctr, Sydney, NSW, Australia..
    Mayoh, Chelsea
    Univ New South Wales, Sch Clin Med, Discipline Paediat & Child Hlth, Sydney, NSW, Australia.;Univ New South Wales, Childrens Canc Inst, Lowy Canc Res Ctr, Sydney, NSW, Australia..
    Mikkel, Sirje
    Univ Tartu, Dept Hematol & Oncol, Tartu, Estonia..
    Myrberg, Ida Hed
    Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden.;Karolinska Inst, Inst Environm Med, Div Biostat, Stockholm, Sweden..
    Niinimäki, Riitta
    Univ Oulu, Oulu Univ Hosp, Dept Children & Adolescents, PEDEGO Res Unit, Oulu, Finland..
    Schmiegelow, Kjeld
    Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark.;Univ Copenhagen, Inst Clin Med, Fac Med, Copenhagen, Denmark..
    Taskinen, Mervi
    Univ Helsinki, Helsinki Univ Hosp, Div Pediat Hematol & Oncol & Stem Cell Transplanta, Helsinki, Finland..
    Vaitkeviciene, Goda
    Vilnius Univ, Vilnius Univ Hosp Santaros Klin, Childrens Hosp, Vilnius, Lithuania..
    Warnqvist, Anna
    Karolinska Inst, Inst Environm Med, Div Biostat, Stockholm, Sweden..
    Wolthers, Benjamin
    Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark..
    Harila-Saari, Arja H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatric oncological and neurological research.
    Ranta, Susanna
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden..
    Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia: phenotypes, risk factors and genotypes2020In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 107, no 10, p. 2318-2328Article in journal (Refereed)
    Abstract [en]

    Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1,464 children aged 1.0-17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1,166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1,464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31-10.20) at 12 months from diagnosis. Patients aged >= 10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P < 0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10(-6)), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients < 10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.

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  • 41.
    Andersen, Christen L.
    et al.
    Dept Haematol, Roskilde Hosp, Roskilde, Denmark.; Dept Haematol, Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark.
    McMullin, Mary F.
    Dept Haematol, Queens Univ Belfast, Antrim, North Ireland.
    Ejerblad, Elisabeth
    Dept Haematol, Univ Uppsala Hosp, Uppsala, Sweden.
    Zweegman, Sonja
    Dept Haematol, Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
    Harrison, Claire
    Dept Haematol, Guys & St Thomas Hosp, London, England; NHS Foundation Trust, London, England.
    Fernandes, Savio
    Bareford, David
    Dept Haematol, Russells Hall Hosp, Dudley, England.
    Knapper, Steven
    Dept Haematol, Cardiff Univ, Cardiff, S Glam, UK.
    Samuelsson, Jan
    Dept Internal Med, Stockholm South Hosp, Stockholm, Sweden.
    Loefvenberg, Eva
    Haematol Ctr, Karolinska Univ Hosp, Stockholm, Sweden.
    Linder, Olle
    Andreasson, Bjorn
    Dept Haematol, NU Hosp Org, Uddevalla Hosp, Uddevalla, Sweden.
    Ahlstrand, Erik
    Örebro University Hospital.
    Jensen, Morten K.
    Dept Haematol, Herlev Hosp, Herlev, Denmark.
    Bjerrum, Ole W.
    Vestergaard, Hanne
    Dept Haematol, Odense Univ Hosp, Odense, Denmark.
    Larsen, Herdis
    Dept Internal Med, Dept Haematol, Viborg Hosp, Viborg, Denmark.
    Klausen, Tobias W.
    Mourits-Andersen, Torben
    Dept Haematol, Esbjerg Cent Hosp, Esbjerg, Denmark.
    Hasselbalch, Hans C.
    Dept Haematol, Roskilde Hosp, Roskilde, Denmark.
    A phase II study of vorinostat (MK-0683) in patients with polycythaemia vera and essential thrombocythaemia2013In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 162, no 4, p. 498-508Article in journal (Refereed)
    Abstract [en]

    Inhibition of histone deacetylases may be an important target in patients with myeloproliferative neoplasms. This investigator-initiated, non-randomized, open-label phase II multi-centre study included 63 patients (19 essential thrombocythaemia, 44 polycythaemia vera) from 15 centres. The primary objective was to evaluate if vorinostat was followed by a decline in clonal myeloproliferation as defined by European Leukaemia Net. Thirty patients (48%) completed the intervention period (24 weeks of therapy). An intention-to-treat response rate of 35% was identified. Pruritus was resolved [19% to 0% (P=0.06)] and the prevalence of splenomegaly was lowered from 50% to 27% (P=0.03). Sixty-five per cent of the patients experienced a decrease in JAK2 V617F allele burden (P=0.006). Thirty-three patients (52% of patients) discontinued study drug before end of intervention due to adverse events (28 patients) or lack of response (5 patients). In conclusion, vorinostat showed effectiveness by normalizing elevated leucocyte and platelet counts, resolving pruritus and significantly reducing splenomegaly. However, vorinostat was associated with significant side effects resulting in a high discontinuation rate. A lower dose of vorinostat in combination with conventional and/or novel targeted therapies may be warranted in future studies.

  • 42. Andersen, Christen Lykkegaard
    et al.
    Bjorn, Mads Emil
    McMullin, Mary Frances
    Harrison, Claire
    Samuelsson, Jan
    Ejerblad, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Zweegman, Sonja
    Fernandes, Savio
    Bareford, David
    Knapper, Steven
    Lofvenberg, Eva
    Linder, Olle
    Andreasson, Bjorn
    Ahlstrand, Erik
    Jensen, Morten Krogh
    Bjerrum, Ole Weis
    Vestergaard, Hanne
    Larsen, Herdis
    Klausen, Tobias Wirenfeldt
    Mourits-Andersen, Torben
    Skov, Vibe
    Thomassen, Mads
    Kruse, Torben
    Gronbaek, Kirsten
    Hasselbalch, Hans Carl
    Circulating YKL-40 in patients with essential thrombocythemia and polycythemia vera treated with the novel histone deacetylase inhibitor vorinostat2014In: Leukemia Research, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 38, no 7, p. 816-821Article in journal (Refereed)
    Abstract [en]

    YKL-40 regulates vascular endothelial growth factors and induces tumor proliferation. We investigated YKL-40 before and after treatment with vorinostat in 31 polycythemia vera (PV) and 16 essential thrombocythemia (ET) patients. Baseline PV patient levels were 2 times higher than in healthy controls (P<0.0001) and 1.7 times higher than in ET (P = 0.02). A significant correlation between YKL-40 at baseline and neutrophils, CRP, LDH, JAK2V617F and platelets in PV patients was observed, as well as a significantly greater reduction of YKL-40 levels in PV patients responding to therapy. YKL-40 might be a novel marker of disease burden and progression in myeloproliferative neoplasms. (C) 2014 Elsevier Ltd. All rights reserved.

  • 43.
    Andersen, Christen Lykkegaard
    et al.
    Dept Hematol, Roskilde Univ Hosp, Roskilde, Denmark..
    Bjorn, Mads Emil
    Dept Hematol, Roskilde Univ Hosp, Roskilde, Denmark..
    McMullin, Mary Frances
    Dept Haematol, Queen Univ Belfast Antrim, Belfast, North Ireland.
    Harrison, Claire
    Dept Haematol, NHS Fdn Trust, London, England.
    Samuelsson, Jan
    Dept Internal Med, Stockholm South Hosp, Stockholm, Sweden..
    Ejerblad, Elisabeth
    Dept Hematol, Univ Uppsala Hosp, Uppsala, Sweden..
    Zweegman, Sonja
    Dept Hematol, Vrije Univ Med Ctr, Amsterdam, Netherlands..
    Fernandes, Savio
    Dept Haematol, Russells Hall Hosp, Dudley, England.
    Bareford, David
    Dept Haematol, Russells Hall Hosp, Dudley, England.
    Knapper, Steven
    Dept Haematol, Cardiff Univ, Cardiff, UK.
    Lofvenberg, Eva
    Hematol Ctr, Karolinska Univ Hosp, Stockholm, Sweden.
    Linder, Olle
    Dept Med, Div Hematol, Örebro Univ Hosp, Örebro, Sweden..
    Andreasson, Bjorn
    Dept Hematol, NU Hosp Org, Uddevalla Hosp, Uddevalla, Sweden.
    Ahlstrand, Erik
    Örebro University Hospital. Dept Med, Div Hematol, Örebro University Hospital, Örebro, Sweden.
    Jensen, Morten Krogh
    Dept Hematol, Herlev Hosp, Herlev, Denmark.
    Bjerrum, Ole Weis
    Dept Hematol, Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark.
    Vestergaard, Hanne
    Dept Hematol, Odense Univ Hosp, Odense, Denmark.
    Larsen, Herdis
    Dept Hematol, Dept Internal Med, Viborg Hosp, Viborg, Denmark.
    Klausen, Tobias Wirenfeldt
    Dept Hematol,Herlev Hosp, Herlev, Denmark.
    Mourits-Andersen, Torben
    Dept Hematol, Esbjerg Cent Hosp, Esbjerg, Denmark.
    Skov, Vibe
    Dept Clin Genet, Odense Univ Hosp, Odense, Denmark.
    Thomassen, Mads
    Dept Clin Genet, Odense Univ Hosp, Odense, Denmark.
    Kruse, Torben
    Dept Clin Genet, Odense Univ Hosp, Odense, Denmark.
    Gronbaek, Kirsten
    Dept Hematol, Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark.
    Hasselbalch, Hans Carl
    Dept Hematol, Roskilde Univ Hosp, Roskilde, Denmark.
    Circulating YKL-40 in patients with essential thrombocythemia and polycythemia vera treated with the novel histone deacetylase inhibitor vorinostat2014In: Leukemia Research, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 38, no 7, p. 816-821Article in journal (Refereed)
    Abstract [en]

    YKL-40 regulates vascular endothelial growth factors and induces tumor proliferation. We investigated YKL-40 before and after treatment with vorinostat in 31 polycythemia vera (PV) and 16 essential thrombocythemia (ET) patients. Baseline PV patient levels were 2 times higher than in healthy controls (P<0.0001) and 1.7 times higher than in ET (P = 0.02). A significant correlation between YKL-40 at baseline and neutrophils, CRP, LDH, JAK2V617F and platelets in PV patients was observed, as well as a significantly greater reduction of YKL-40 levels in PV patients responding to therapy. YKL-40 might be a novel marker of disease burden and progression in myeloproliferative neoplasms.

  • 44. Andersen, Mette K.
    et al.
    Autio, Kirsi
    Barbany, Gisela
    Borgstroem, Georg
    Cavelier, Lucia
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Heim, Sverre
    Heinonen, Kristina
    Hovland, Randi
    Johannsson, Johann H.
    Johansson, Bertil
    Kjeldsen, Eigil
    Nordgren, Ann
    Palmqvist, Lars
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Paediatric B-cell precursor acute lymphoblastic leukaemia with t(1;19)(q23;p13): clinical and cytogenetic characteristics of 47 cases from the Nordic countries treated according to NOPHO protocols2011In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 155, no 2, p. 235-243Article in journal (Refereed)
    Abstract [en]

    The translocation t(1;19)(q23;p13)/der(19) t(1;19) is a risk stratifying aberration in childhood B-cell precursor acute lymphoblastic leukaemia (BCP ALL) in the Nordic countries. We have identified 47 children/adolescents with t(1;19)/der(19) t(1;19)-positive BCP ALL treated on two successive Nordic Society of Paediatric Haematology and Oncology (NOPHO) protocols between 1992 and 2007 and have reviewed the clinical and cytogenetic characteristics of these cases, comprising 1.8% of all cases. The translocation was balanced in 15 cases (32%) and unbalanced in 29 cases (62%). The most common additional chromosome abnormalities were del(9p), i(9q), del(6q), and del(13q). The median age was 7 years, the median white blood cell (WBC) count was 16 x 10(9)/l, and the female/male ratio was 1.2. The predicted event-free survival (EFS) at 5 and 10 years was 0.79, whereas the predicted overall survival (OS) at 5 and 10 years was 0.85 and 0.82, respectively. Nine patients had a bone marrow relapse after a median of 23 months; no patient had a central nervous system relapse. Additional cytogenetic abnormalities, age, gender, WBC count or whether the t(1;19) was balanced or unbalanced did not influence EFS or OS. Compared to cases with t(12,21) and high hyperdiploidy, EFS was similar, but overall survival was worse in patients with t(1;19)/der(19) t(1;19) (P = 0.004).

  • 45.
    Anderzen-Carlsson, Agneta
    et al.
    Örebro University, School of Health Sciences. Örebro University Hospital.
    Leibring, I.
    Karlstad University, Faculty of Health- Science and Technology- Department of Health Sciences- Nursing, Karlstad, Sweden.
    Fear and Coping During Treatment for Acute Lymphatic Leukemia - from the Perspective of Children 5-9 Years Old2018In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 65, no Suppl.2, p. S598-S598Article in journal (Other academic)
    Abstract [en]

    Background/Objectives: The concept of fear can be defined as ”an unpleasant often strong emotion caused by expectation of danger”. It is reasonable to believe that fear and coping of fear, can vary during the course of treatment for ALL. The aim of the present study was to describe a longitudinal perspective on fear related to having ALL, based on children's perspective, as well as to describe the strategies these children use when experiencing fear.

    Design/Methods: The study has a longitudinal descriptive qualitative design. Three girls and 10 boys, initially aged 5-9 were interviewed once to three times during their treatment period (approximately two months after the diagnosis, after one year and at the end of the 2.5-year long treatment). In total, 35 interviews were conducted. Data were analyzed using a matrix-based qualitative analysis method.

    Results: The children described fear of being subjected to needles and related to having a feeding tube, removing adhesive tape and taking tablets, as well as fear related to the bodily changes caused by the ALL. Existential fears were most frequently mentioned at the end of treatment. The children wanted to participate i n their care. They used cognitive strategies, such as ”thinking the right way” and emotional strategies, such as crying out loud and kicking. The fears changed over time, but the fear of being subjected to needles remained for half of the children, but was less intense at the end of treatment. The strategies developed, and became more sophisticated over the treatment period.

    Conclusions: The fear changed throughout the course of treatment, and so did the strategies used. It is reasonable to believe that the need for support also vary, which i s a topic for future research.

  • 46.
    Andreasson, A.
    et al.
    Karolinska Inst Huddinge, Stockholm, Sweden..
    Uttervall, K.
    Karolinska Inst, Stockholm, Sweden..
    Liwing, J.
    Janssen AB, Sollentuna, Sweden..
    Alici, E.
    Karolinska Inst, Stockholm, Sweden..
    Näsman, Per
    KTH, School of Architecture and the Built Environment (ABE).
    Aschan, J.
    Janssen AB, Sollentuna, Sweden..
    Nahi, H.
    Karolinska Inst, Stockholm, Sweden..
    Bortezomib, response and retreatment in 1st, 2nd, 3rd and 4th line of treatment in patients with multiple myeloma2012In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 97, p. 610-610Article in journal (Other academic)
  • 47. Andrews, Robert K.
    et al.
    Wolberg, Alisa
    Lip, Gregory Y. H.
    Eikelboom, John
    De Meyer, Simon F.
    Mast, Alan
    Flick, Matthew
    Urano, Tetsumei
    Ny, Tor
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Cutler, Daniel
    Ju, Lining A.
    Zhu, Cheng
    Randi, Anna M.
    O'Donnell, James S.
    O'Brien, Sarah H.
    Fijnvandraat, Karin
    Shima, Midori
    Nathwani, Amit
    Luyendyk, Jim
    Vanhoorelbeke, Karen
    Barco, Stefano
    Chuansumrit, Ampaiwan
    Stanworth, Simon J.
    Curry, Nicola
    Del Rio, J. Mauricio
    Battinelli, Elisabeth M.
    Bos, Mettine H. A.
    Reinhardt, Christoph
    Peter, Karlheinz
    Gomez, Keith
    Danese, Elisa
    Rak, Janusz
    Flaumenhaft, Robert
    Di Paola, Jorge
    Nilsson, Susie
    Severin, Sonia
    Eto, Koji
    Hitchcock, Ian S.
    Ni, Heyu
    Despotovic, Jenny
    Boilard, Eric
    Rondina, Matthew
    Mangin, Pierre
    Hamilton, Justin R.
    Suzuki-Inoue, Katsue
    Tsukiji, Nagaharu
    Conway, Edward M.
    Maas, Coen
    Emsley, Jonas
    Jenne, Craig N.
    Fuchs, Tobias A.
    Weitz, Jeffrey
    Johnsen, Jill M.
    Rauova, Lubica
    Spyropoulos, Alex
    Goto, Shinya
    Verhamme, Peter
    Miranda, Sebastien
    Rodger, Marc
    Ni Ainle, Fionnuala
    Schreiber, Karen
    Thomas, Moumneh
    Le Gal, Gregoire
    Zentner, Dominica
    McLintock, Claire
    Magnusson, Maria
    Illustrated State-of-the-Art Capsules of the ISTH 2019 Congress in Melbourne, Australia: Plasminogen in wound healing2019In: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS, ISSN 2475-0379, Vol. 3, no 3, p. 431-497Article, review/survey (Refereed)
    Abstract [en]

    The 27th Congress of the International Society of Thrombosis and Haemostasis (ISTH) is an international conference held July 6-10, 2019, in Melbourne, the capital of the state of Victoria, Australia. The ISTH congress has previously been held every other year, with the Scientific and Standardization Committee (SSC) meeting held annually, until 2019 when it became one combined annual meeting of the ISTH and SSC. The conference covers clinical and basic aspects of hemostasis and thrombosis, and this year includes 5 Plenary lectures and >50 State of Art (SOA) lectures, presented by internationally recognized speakers, as well as numerous oral session and poster presentations selected from submitted abstracts, including many early career and reach the world support recipients. This SOA review article in RPTH contains concise Illustrated Review Articles or 'Capsules' consisting of short text, three references and a figure, with topics including stroke, cancer-associated thrombosis, hemophilia, coagulation, the interface between infection and inflammation, and in the experimental and discovery areas, megakaryocyte biology and platelet production, structure-function of key receptors and coagulation factors, and emerging new roles for thrombotic/hemostatic factors. Together, these articles highlight novel findings which will advance knowledge and with the potential to change clinical practice and improve outcomes. It is hoped that conference attendees and followers will enjoy utilizing the images for ongoing education and during the conference for live tweeting during sessions, to assist in the broadcasting and promotion of the science to those unable to attend, or who have chosen to attend a concurrent session. Use #IllustratedReview and #ISTH2019 on social media.

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  • 48.
    Andrés-Jensen, Liv
    et al.
    Copenhagen Univ Hosp, Rigshosp, Dept Pediat & Adolescent Med, DK-2100 Copenhagen, Denmark.
    Attarbaschi, Andishe
    Med Univ Vienna, St Anna Childrens Hosp, Dept Pediat Hematol Oncol, Vienna, Austria.
    Bardi, Edit
    Med Univ Vienna, St Anna Childrens Hosp, Dept Pediat Hematol Oncol, Vienna, Austria; Kepler Univ Clin, Dept Pediat Oncol & Immunol, Linz, Austria.
    Barzilai-Birenboim, Shlomit
    Schneider Childrens Med Ctr Israel, Dept Pediat Hematol Oncol, Petah Tiqwa, Israel; Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.
    Bhojwani, Deepa
    Univ Southern Calif, Keck Sch Med, Childrens Hosp Los Angeles, Dept Pediat,Norris Comprehens Canc Ctr, Los Angeles, CA 90007 USA.
    Hagleitner, Melanie M.
    Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands.
    Halsey, Christina
    Univ Glasgow, Coll Med Vet & Life Sci, Inst Canc Sci, Wohl Canc Res Ctr, Glasgow, Lanark, Scotland; Royal Hosp Children, Childrens Haematooncol Unit, Glasgow, Lanark, Scotland.
    Harila-Saari, Arja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    van Litsenburg, Raphaele R. L.
    Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands.
    Hudson, Melissa M.
    St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA.
    Jeha, Sima
    Kato, Motohiro
    Univ Tokyo, Dept Pediat, Tokyo, Japan.
    Kremer, Leontien
    Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands.
    Mlynarski, Wojciech
    Med Univ Lodz, Dept Pediat Oncol & Hematol, Lodz, Poland.
    Möricke, Anja
    Christian Albrechts Univ Kiel, Univ Med Ctr Schleswig Holstein, Dept Pediat, Kiel, Germany.
    Pieters, Rob
    Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands.
    Piette, Caroline
    Univ Hosp Liege, Dept Paediat, Liege, Belgium; Univ Liege, Liege, Belgium.
    Raetz, Elizabeth
    NYU, Langone Med Ctr, Dept Pediat, New York, NY USA.
    Ronceray, Leila
    Med Univ Vienna, St Anna Childrens Hosp, Dept Pediat Hematol Oncol, Vienna, Austria.
    Toro, Claudia
    Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
    Valsecchi, Maria Grazia
    Univ Milan, Sch Med & Surg, Bicocca Ctr Bioinformat Biostat & Bioimaging, Monza, Italy.
    Vrooman, Lynda M.
    Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
    Weinreb, Sigal
    Hadassah Hebrew Univ, Med Ctr, Dept Pediat Hematol Oncol, Jerusalem, Israel.
    Winick, Naomi
    Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA.
    Schmiegelow, Kjeld
    Copenhagen Univ Hosp, Rigshosp, Dept Pediat & Adolescent Med, DK-2100 Copenhagen, Denmark; Univ Copenhagen, Fac Med, Inst Clin Med, Copenhagen, Denmark.
    Severe toxicity free survival: physician-derived definitions of unacceptable long-term toxicities following acute lymphocytic leukaemia2021In: The Lancet Haematology, E-ISSN 2352-3026, Vol. 8, no 7, p. E513-E523Article, review/survey (Refereed)
    Abstract [en]

    5-year overall survival rates have surpassed 90% for childhood acute lymphocytic leukaemia, but survivors are at risk for permanent health sequelae. Although event-free survival appropriately represents the outcome for cancers with poor overall survival, this metric is inadequate when cure rates are high but challenged by serious, persistent complications. Accordingly, a group of experts in paediatric haematology-oncology, representative of 17 international acute lymphocytic leukaemia study groups, launched an initiative to construct a measure, designated severe toxicity-free survival (STFS), to quantify the occurrence of physician-prioritised toxicities to be integrated with standard cancer outcome reporting. Five generic inclusion criteria (not present before cancer diagnosis, symptomatic, objectifiable, of unacceptable severity, permanent, or requiring unacceptable treatments) were used to assess 855 health conditions, which resulted in inclusion of 21 severe toxicities. Consensus definitions were reached through a modified Delphi process supplemented by two additional plenary meetings. The 21 severe toxicities include severe adverse health conditions that substantially affect activities of daily living and are refractory to therapy (eg, refractory seizures), are without therapeutic options (eg, blindness), or require substantially invasive treatment (eg, cardiac transplantation). Incorporation of STFS assessment into clinical trials has the potential to improve and diversify treatment strategies, focusing not only on traditional outcome events and overall survival but also the frequencies of the most severe toxicities. The two major aims of this Review were to: prioritise and define unacceptable long-term toxicity for patients with childhood acute lymphocytic leukaemia, and define how these toxicities should be combined into a composite quantity to be integrated with other reported outcomes. Although STFS quantifies the clinically unacceptable health tradeoff for cure using childhood acute lymphocytic leukaemia as a model disease, the prioritised severe toxicities are based on generic considerations of relevance to any other cancer diagnosis and age group.

  • 49.
    Angenendt, Linus
    et al.
    Univ Hosp Munster, Munster, Germany.
    Röllig, Christoph
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Montesinos, Pau
    Hosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain.
    Martinez-Cuadron, David
    Hosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain.
    Barragan, Eva
    Hosp Univ & Politec La Fe, Valencia, Spain;Ctr Invest Biomed Red Canc, Madrid, Spain.
    Garcia, Raimundo
    Gen Hosp Castellon, Castellon de La Plana, Spain.
    Botella, Carmen
    Hosp Gen Alicante, Alicante, Spain.
    Martinez, Pilar
    Hosp 12 Octubre, Madrid, Spain.
    Ravandi, Farhad
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Kadia, Tapan
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Kantarjian, Hagop M.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Cortes, Jorge
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Juliusson, Gunnar
    Lund Univ, Lund, Sweden.
    Lazarevic, Vladimir
    Lund Univ, Lund, Sweden.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Lehmann, Sören
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Recher, Christian
    CHU Toulouse, Toulouse, France.
    Pigneux, Arnaud
    CHU Bordeaux, Hop Haut Leveque, Bordeaux, France.
    Bertoli, Sarah
    CHU Toulouse, Toulouse, France.
    Dumas, Pierre-Yves
    CHU Bordeaux, Hop Haut Leveque, Bordeaux, France.
    Dombret, Herve
    Paris Diderot Univ, Paris, France.
    Preudhomme, Claude
    Inst Natl Sante & Rech Med Lille, Lille, France.
    Micol, Jean-Baptiste
    Paris Saclay Univ, Gustave Roussy, Villejuif, France.
    Terre, Christine
    Ctr Transfus Sanguine, Le Chesnay, France.
    Racil, Zdenek
    Masaryk Univ, Univ Hosp Brno, Brno, Czech Republic.
    Novak, Jan
    Charles Univ Prague, Univ Hosp Kralovske Vinohrady, Fac Med 3, Prague, Czech Republic.
    Zak, Pavel
    Charles Univ Prague, Univ Hosp Hradec Kralove, Hradec Kralove, Czech Republic.
    Wei, Andrew H.
    Monash Univ, Alfred Hosp, Melbourne, Vic, Australia.
    Tiong, Ing S.
    Monash Univ, Alfred Hosp, Melbourne, Vic, Australia.
    Wall, Meaghan
    St Vincents Hosp, Melbourne, Vic, Australia.
    Estey, Elihu
    Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
    Shaw, Carole
    Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
    Exeler, Rita
    Univ Munster, Munster, Germany.
    Wagenführ, Lisa
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Stölzel, Friedrich
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Thiede, Christian
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Stelljes, Matthias
    Univ Hosp Munster, Munster, Germany.
    Lenz, Georg
    Univ Hosp Munster, Munster, Germany.
    Mikesch, Jan-Henrik
    Univ Hosp Munster, Munster, Germany.
    Serve, Hubert
    Univ Hosp Frankfurt, Frankfurt, Germany.
    Ehninger, Gerhard
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Berdel, Wolfgang E.
    Univ Hosp Munster, Munster, Germany.
    Kramer, Michael
    Tech Univ Dresden, Univ Hosp, Dresden, Germany.
    Krug, Utz
    Klinikum Leverkusen, Leverkusen, Germany.
    Schliemann, Christoph
    Univ Hosp Munster, Munster, Germany.
    Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia: A Pooled Analysis of Individual Patient Data From Nine International Cohorts2019In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 37, no 29, p. 2632-2642Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Nucleophosmin 1 (NPM1) mutations are associated with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms-related tyrosine kinase 3 gene (FLT3) is absent (FLT3-ITDneg) or present with a low allelic ratio (FLT3-ITDlow). The 2017 European LeukemiaNet guidelines assume this is true regardless of accompanying cytogenetic abnormalities. We investigated the validity of this assumption.

    METHODS: We analyzed associations between karyotype and outcome in intensively treated patients with NPM1(mut)/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers.

    RESULTS: Among 2,426 patients with NPM1(mut)/FLT3-ITDneg/low AML, 2,000 (82.4%) had a normal and 426 (17.6%) had an abnormal karyotype, including 329 patients (13.6%) with intermediate and 83 patients (3.4%) with adverse-risk chromosomal abnormalities. In patients with NPM1(mut)/FLT3-ITDneg/low AML, adverse cytogenetics were associated with lower complete remission rates (87.7%, 86.0%, and 66.3% for normal, aberrant intermediate, and adverse karyotype, respectively; P < .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P < .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P < .001), and a higher 5-year cumulative incidence of relapse (43.6%, 44.2%, 51.9%, respectively; P = .0012). These associations remained in multivariable mixed-effects regression analyses adjusted for known clinicopathologic risk factors (P < .001 for all end points). In patients with adverse-risk chromosomal aberrations, we found no significant influence of the NPM1 mutational status on outcome.

    CONCLUSION: Karyotype abnormalities are significantly associated with outcome in NPM1(mut)/FLT3-ITDneg/low AML. When adverse-risk cytogenetics are present, patients with NPM1(mut) share the same unfavorable prognosis as patients with NPM1 wild type and should be classified and treated accordingly. Thus, cytogenetic risk predominates over molecular risk in NPM1(mut)/FLT3-ITDneg/low AML.

  • 50.
    Apollonio, Benedetta
    et al.
    Kings Coll London, Dept Haematooncol, London WC2R 2LS, England..
    Nicholas, Nicole S.
    Kings Coll London, Dept Haematooncol, London WC2R 2LS, England..
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Salisbury, Jon
    Kings Coll Hosp London, London, England..
    Patten, Piers E.
    Kings Coll Hosp London, Haematol, London, England..
    Kassam, Shireen
    Kings Coll Hosp London, London, England..
    Devereux, Stephen
    Kings Coll Hosp London, Haematol, London, England..
    Amini, Rose Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ramsay, Alan G.
    Kings Coll London, Dept Haematooncol, London WC2R 2LS, England..
    Diffuse Large B-Cell Lymphoma (DLBCL) Tumor Cells Reprogram Lymphatic Fibroblasts into Cancer-Associated Fibroblasts (CAFs) That Contribute to Tumor Microenvironment (TME)-Driven Immune Privilege2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
1234567 1 - 50 of 1587
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