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  • 1.
    Burman, Joachim
    et al.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden; Department of Neurology, Uppsala University Hospital, Uppsala, Sweden .
    Iacobaeus, Ellen
    Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institute Solna, Center for Molecular Medicine, Stockholm, Sweden.
    Svenningsson, Anders
    Department of Pharmacology and Clinical Neuroscience, Umeå University and University Hospital of Northern Sweden, Umeå, Sweden .
    Lycke, Jan
    Department of Neurology, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Gunnarsson, Martin
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Neurology, Örebro University Hospital, Örebro, Sweden .
    Nilsson, Petra
    Department of Neurology, Skåne University Hospital Lund, Lund, Sweden.
    Vrethem, Magnus
    Neurology and Clinical Neurophysiology, Faculty of Health Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Neurology and Neurophysiology, County Council of Östergötland, Linköping, Sweden .
    Fredrikson, Sten
    Department of Clinical Neuroscience, Karolinska Institute Huddinge, Stockholm, Sweden .
    Martin, Claes
    Neurology Unit, Division of Internal Medicine, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden .
    Sandstedt, Anna
    Department of Hematology, Linköping University Hospital, Linköping, Sweden .
    Uggla, Bertil
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Division of Hematology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Lenhoff, Stig
    Department of Hematology and Coagulation, Skåne University Hospital, Lund, Sweden .
    Johansson, Jan-Erik
    Department of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Isaksson, Cecilia
    Department of Radiosciences, Umeå University, Umeå, Sweden .
    Hägglund, Hans
    Division of Hematology, Department of Medical Science, Uppsala University Hospital, Uppsala, Sweden.
    Carlson, Kristina
    Division of Hematology, Department of Medical Science, Uppsala University Hospital, Uppsala, Sweden.
    Fagius, Jan
    Department of Neuroscience, Uppsala University, Uppsala, Sweden; Department of Neurology, Uppsala University Hospital, Uppsala, Sweden .
    Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience2014In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, no 10, p. 1116-1121Article in journal (Refereed)
    Abstract [en]

    Background: Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS.

    Methods: Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months.

    Results: At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%).

    Conclusions: HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.

  • 2.
    Deneberg, Stefan
    et al.
    Department of Internal Medicine/Hematology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Guardiola, Philippe
    Inserm, Angers, France; Service des Maladies du Sang, Centre Hospitalier Universitaire, Angers, France.
    Lennartsson, Andreas
    Institute for Biomedicine and Nutrition, NOVUM, Karolinska Institutet, Stockholm, Sweden.
    Qu, Ying
    Department of Internal Medicine/Hematology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Gaidzik, Verena E.
    Department of Internal Medicine III, University Hospital, Ulm, Germany.
    Blanchet, Odile
    Inserm, Angers, France; Laboratoire d Hematologie, Centre Hospitalier Universitaire, Angers, France.
    Karimi, Mohsen
    Department of Internal Medicine/Hematology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Bengtzén, Sofia
    Department of Internal Medicine/Hematology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Nahi, Hareth
    Department of Internal Medicine/Hematology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Uggla, Bertil
    Örebro University, School of Medical Sciences. Department of Hematology, Örebro University Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Hematology, Örebro University Hospital, Örebro, Sweden.
    Höglund, Martin
    Department of Hematology, Uppsala University Hospital, Uppsala, Sweden.
    Paul, Christer
    Department of Internal Medicine/Hematology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Ekwall, Karl
    Institute for Biomedicine and Nutrition, NOVUM, Karolinska Institutet, Stockholm, Sweden.
    Döhner, Konstanze
    Department of Internal Medicine III, University Hospital, Ulm, Germany.
    Lehmann, Sören
    Department of Internal Medicine/Hematology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Prognostic DNA methylation patterns in cytogenetically normal acute myeloid leukemia are predefined by stem cell chromatin marks2011In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, no 20, p. 5573-5582Article in journal (Refereed)
    Abstract [en]

    Cytogenetically normal acute myeloid leukemia (CN-AML) comprise between forty and fifty percent of all adult acute myeloid leukemia (AML) cases. In this clinically diverse group molecular aberrations such as FLT3ITD, NPM1 and CEBPA mutations recently have added to the prognostic accuracy. Aberrant DNA methylation is a hallmark of cancer including AML. We investigated in total 118 CN-AML samples in a test and a validation cohort for genome-wide promoter DNA methylation with Illumina Methylation Bead arrays and compared them to normal myeloid precursors and global gene expression. IDH and NPM1 mutations were associated with different methylation patterns (p=0.0004 and 0.04, respectively). Genome-wide methylation levels were elevated in IDH mutated samples (p=0.006). We observed a negative impact of DNA methylation on transcription. Genes targeted by Polycomb group (PcG) proteins and genes associated with bivalent histone marks in stem cells showed increased aberrant methylation in AML (p<0.0001). Furthermore, high methylation levels of PcG target genes were independently associated with better progression free (OR 0.47, p=0.01) and overall survival (OR 0.36, p=0.001). In summary, genome wide methylation patterns show preferential methylation of PcG targets with prognostic impact in CN-AML.

  • 3.
    Derolf, Åsa
    et al.
    Department of Hematology, Karolinska University Hospital, Stockholm, Sweden; Department of Internal Medicine, Karolinska Institutet, Stockholm, Sweden.
    Juliusson, Gunnar
    Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund.
    Benson, Lina
    Epidemiology and Regional Oncologic Center in Stockholm, Stockholm, Sweden.
    Fløisand, Yngvar
    Department of Hematology, Oslo University Hospital, Oslo, Norway.
    Lazarevic, Vladimir
    Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund.
    Antunovic, Petar
    Department of Hematology, Linköping University Hospital, Linköping, Sweden.
    Möllgård, Lars
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Lehmann, Soren
    Department of Medical Sciences, Unit of Haematology, Uppsala University, Uppsala, Sweden.
    Uggla, Bertil
    Örebro University, School of Medical Sciences.
    Wahlin, Anders
    Department of Radiation Sciences, Umeå University, Umeå, Sweden.
    Höglund, Martin
    Department of Medical Sciences, Unit of Haematology, Uppsala University, Uppsala, Sweden.
    Deneberg, Stefan
    Department of Hematology, Karolinska University Hospital, Stockholm, Sweden; Department of Internal Medicine, Karolinska Institutet, Stockholm, Sweden.
    Decreasing early mortality in acute myeloid leukaemia in Sweden 1997-2014: improving performance status is a major contributing factor2020In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 188, no 1, p. 187-191Article in journal (Refereed)
  • 4.
    Ekbäck, Maria [Palmetun]
    et al.
    Department of Dermatology, Örebro University Hospital, Örebro, Sweden; Department of Medicine, Örebro University, Örebro, Sweden.
    Uggla, Bertil
    Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden.
    Paraneoplastic pemphigus associated with chronic lymphocytic leukaemia: treatment with alemtuzumab2012In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 36, no 8, p. E190-E191Article in journal (Refereed)
  • 5.
    Kozlowski, Piotr
    et al.
    Division of Hematology, Department of Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Kameran Behnam, Klodia
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Uggla, Bertil
    Örebro University, School of Medical Sciences. Division of Hematology.
    Åström, Maria
    Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Hematology.
    Carfilzomib-induced hemolysis is noticeably common but rarely shows features of thrombotic microangiopathy: A retrospective study2020In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 104, no 6, p. 588-593Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Hemolysis is a sporadically reported but potentially serious side effect of the proteasome inhibitor carfilzomib. We aimed to investigate the frequency of hemolysis in an unselected cohort.

    METHODS: We performed a retrospective, single-center study of the incidence of hemolysis in patients treated with carfilzomib, based mainly on consecutive haptoglobin levels. The patients were diagnosed with myeloma (n = 20), AL amyloidosis (n = 3), and light-chain deposition disease (n = 1). Carfilzomib treatment was applied after a median of 3 (range: 1-7) therapy lines.

    RESULTS: Haptoglobin levels were normal/increased before, generally suppressed during, and normalized after treatment with carfilzomib. Very low haptoglobin (<0.1 g/L) implying the presence of hemolysis was observed in 16 of 24 (67%) patients during carfilzomib therapy. Hemolysis was mild in 11 of 16 (69%) affected patients, whereas 5 of 16 (31%) required transfusion. Severe hemolysis was explained by thrombotic microangiopathy (TMA) in one patient who died of the complication. Mechanisms were unclear in the remaining 15 patients.

    CONCLUSIONS: Hemolysis was surprisingly common but mostly mild during carfilzomib treatment. However, the possibility of TMA should be kept in mind in this setting. Hypothetically, non-TMA hemolysis could be attributed to the accumulation of globin chains due to the suppression of eukaryotic translation initiation inhibition by carfilzomib.

  • 6.
    Lazarevic, V.
    et al.
    Department of Hematology and Coagulation, Skåne University Hospital, Lund, Sweden; Department of Hematology/Transplantation, Stem Cell Center, Lund University, Lund, Sweden.
    Hörstedt, A-S.
    Regional Cancer Center in South Sweden, Skåne University Hospital, Lund, Sweden.
    Johansson, B.
    Department of Clinical Genetics, University and Regional Laboratories Region Skåne, Lund, Sweden; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
    Antunovic, P.
    Department of Hematology, Linköping University Hospital, Linköping, Sweden.
    Billström, R.
    Department of Medicine, Central Hospital Skövde, Skövde, Sweden.
    Derolf, A.
    Hematology Center, Karolinska University Hospital, Stockholm, Sweden.
    Hulegårdh, E.
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Lehmann, S.
    Hematology Center, Karolinska University Hospital, Stockholm, Sweden.
    Möllgård, L.
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Nilsson, C.
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Peterson, S.
    Regional Cancer Center in South Sweden, Skåne University Hospital, Lund, Sweden.
    Stockelberg, D.
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Uggla, Bertil
    Örebro University Hospital. Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Wennström, L.
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Wahlin, A.
    Department of Radiation Sciences, Umeå University, Umeå, Sweden.
    Höglund, M.
    Department of Hematology, Academic Hospital, Uppsala, Sweden.
    Juliusson, G.
    Department of Hematology and Coagulation, Skåne University Hospital, Lund, Sweden; Department of Hematology/Transplantation, Stem Cell Center, Lund University, Lund, Sweden.
    Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience2014In: Blood Cancer Journal, ISSN 2044-5385, E-ISSN 2044-5385, Vol. 4, no 2, article id e188Article in journal (Refereed)
    Abstract [en]

    The Swedish population-based acute myeloid leukemia registry contains data from 3251 patients (excluding acute promyelocytic leukemia) diagnosed between 1997 and 2006. Informative cytogenetic data from 1893 patients were retrospectively added, including 1054 patients aged between 60 and 79 years. Clonal abnormalities were found in 57% of the informative karyotypes. Karyotypic patterns differed by age: t(8;21), inv(16) and t(11q23) were more common in younger patients, whereas loss of 5q, 7q and 17p, monosomal karyotype (MK) and complex karyotypes were more common in older patients. Loss of 5q, 7q and 17p often occurred together within MK. Patients with 5 chromosome abnormalities had worse overall survival than those with fewer abnormalities or normal karyotype in all age groups. Loss of 5q, 7q and/or 17p had, in contrast to MK, a further negative impact on survival. Multivariable Cox regression analyses on risk factors in patients <80 years with cytogenetic abnormalities and intensive treatment revealed that age and performance status had the most significant impact on survival (both P<0.001), followed by sex (P=0.0135) and a karyotype including -7/del(7q) (P=0.048).

  • 7.
    Lazarevic, Vladimir
    et al.
    Department of Hematology and Coagulation, Skåne University Hospital, Lund, Sweden; Stem Cell Center, Lund University, Lund, Sweden.
    Hörstedt, Ann-Sofi
    Regional Cancer Center in South Sweden, Skåne University Hospital, Lund, Sweden.
    Johansson, Bertil
    Department of Clinical Genetics, Regional Laboratories, Region Skåne, Lund, Sweden; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden; .
    Antunovic, Petar
    Department of Hematology, Linköping University Hospital, Linköping, Sweden.
    Billström, Rolf
    , SwedenDepartment of Medicine, Central Hospital Skövde, Sweden.
    Derolf, Asa
    Department of Medicine, Division of Hematology, Karolinska University Hospital, Stockholm, Sweden.
    Lehmann, Sören
    Department of Medicine, Division of Hematology, Karolinska University Hospital, Stockholm, Sweden.
    Möllgård, Lars
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Peterson, Stefan
    Regional Cancer Center in South Sweden, Skåne University Hospital, Lund, Sweden.
    Stockelberg, Dick
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Uggla, Bertil
    Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Vennström, Lovisa
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Wahlin, Anders
    Department of Radiation Sciences, Umeå University, Umeå, Sweden.
    Höglund, Martin
    Department of Hematology, Academic Hospital, Uppsala, Sweden.
    Juliusson, Gunnar
    Department of Hematology and Coagulation, Skåne University Hospital, Lund, Sweden; Stem Cell Center, Lund University, Lund, Sweden.
    Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia2015In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 94, no 5, p. 419-423Article in journal (Refereed)
    Abstract [en]

    Unsuccessful cytogenetics (UC) in patients with acute myeloid leukaemia (AML) treated on different SWOG trials was recently reported to be associated with increased age and dismal outcome. To ascertain whether this holds true also in unselected patients with AML, we retrieved all cytogenetic reports in cases from the population-based Swedish AML Registry. Between 1997 and 2006, 1737 patients below 80 yr of age without myelosarcoma or acute promyelocytic leukaemia received intensive treatment. The frequencies of UC and unperformed cytogenetics (UPC) were 2.1% and 20%, respectively. The early death rates differed between the cytogenetic subgroups (P = 0.006) with the highest rates in patients with UC (14%) and UPC (12%) followed by high-risk (HR) AML, intermediate risk (IR) and standard risk (SR) cases successfully karyotyped (8.6%, 5.9%, and 5.8%, respectively). The complete remission rate was lower in UC and UPC and HR compared with the other risk groups (P < 0.001). The overall five-year survival rates were 25% for UC and 22% for UPC, whereas the corresponding frequencies for SR, IR and HR AML patients without UC and UPC were 64%, 31% and 15%, respectively. In conclusion, lack of cytogenetic data translates into a poor prognosis.

  • 8.
    Lazarevic, Vladimir Lj
    et al.
    Skåne University Hospital, Lund, Sweden; Stem Cell Center, Lund University, Lund, Sweden.
    Rosso, Aldana
    Skåne University Hospital, Lund, Sweden; Lund University, Lund, Sweden.
    Juliusson, Gunnar
    Skåne University Hospital, Lund, Sweden; Stem Cell Center, Lund University, Lund, Sweden.
    Antunovic, Petar
    Linköping University Hospital, Linköping, Sweden.
    Derolf, Åsa Rangert
    Karolinska University Hospital, Stockholm, Sweden.
    Deneberg, Stefan
    Karolinska University Hospital, Stockholm, Sweden.
    Möllgård, Lars
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Uggla, Bertil
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Wennström, Lovisa
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Wahlin, Anders
    Umeå University, Umeå, Sweden.
    Höglund, Martin
    Academic Hospital, Uppsala, Sweden.
    Lehmann, Sören
    Academic Hospital, Uppsala, Sweden.
    Johansson, Bertil
    University and Regional Laboratories, Region Skåne, Lund, Sweden; Lund University, Lund, Sweden.
    Incidence and prognostic significance of isolated trisomies in adult acute myeloid leukemia: A population-based study from the Swedish AML registry2017In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 98, no 5, p. 493-500Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES AND METHODS: To ascertain the incidence/clinical implications of isolated autosomal trisomies in adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry.

    RESULTS: Of the 3179 cytogenetically informative AMLs diagnosed January 1997-May 2015, 246 (7.7%) had isolated trisomies. The frequency increased by age (2.4% at age 18-60 years vs. 23% at >60 years; P<.0001); the median age was 69 years. The five most common were +8 (4.0%), +13 (0.9%), +11 (0.8%), +21 (0.7%), and +4 (0.5%). Age and gender, types of AML and treatment, and complete remission and early death rates did not differ between the single trisomy and the intermediate risk (IR) groups or among cases with isolated gains of chromosomes 4, 8, 11, 13, or 21. The overall survival (OS) was similar in the single trisomy (median 1.6 years) and IR groups (1.7 years; P=.251). The OS differed among the most frequent isolated trisomies; the median OS was 2.5 years for +4, 1.9 years for +21, 1.5 years for +8, 1.1 years for +11, and 0.8 years for +13 (P=.013).

    CONCLUSION: AML with single trisomies, with the exception of +13, should be grouped as IR.

  • 9. Lehmann, S
    et al.
    Bykov, VJ
    Ali, D
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Cherif, H
    Tidefelt, Ulf
    Örebro University, School of Medicine, Örebro University, Sweden.
    Uggla, Bertil
    Örebro University, School of Medicine, Örebro University, Sweden.
    Yachnin, J
    Juliusson, G
    Moshfegh, A
    Paul, C
    Wiman, KG
    Andersson, PO
    Targeting p53 in vivo: a first-in-man study with the p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 29, p. 3633-3639Article in journal (Refereed)
    Abstract [en]

    PURPOSE: APR-246 (PRIMA-1MET) is a novel drug that restores transcriptional activity of unfolded wild-type or mutant p53. The main aims of this first-in-human trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of APR-246.

    PATIENTS AND METHODS: APR-246 was administered as a 2-hour intravenous infusion once per day for 4 consecutive days in 22 patients with hematologic malignancies and prostate cancer. Acute myeloid leukemia (AML; n = 7) and prostate cancer (n = 7) were the most frequent diagnoses. Starting dose was 2 mg/kg with dose escalations up to 90 mg/kg.

    RESULTS: MTD was defined as 60 mg/kg. The drug was well tolerated, and the most common adverse effects were fatigue, dizziness, headache, and confusion. DLTs were increased ALT/AST (n = 1), dizziness, confusion, and sensory disturbances (n = 2). PK showed little interindividual variation and were neither dose nor time dependent; terminal half-life was 4 to 5 hours. Tumor cells showed cell cycle arrest, increased apoptosis, and upregulation of p53 target genes in several patients. Global gene expression analysis revealed changes in genes regulating proliferation and cell death. One patient with AML who had a p53 core domain mutation showed a reduction of blast percentage from 46% to 26% in the bone marrow, and one patient with non-Hodgkin's lymphoma with a p53 splice site mutation showed a minor response.

    CONCLUSION: We conclude that APR-246 is safe at predicted therapeutic plasma levels, shows a favorable pharmacokinetic profile, and can induce p53-dependent biologic effects in tumor cells in vivo.

  • 10.
    Lehmann, Sören
    et al.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Unit of Hematology, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
    Deneberg, Stefan
    Unit of Hematology, Department of Medicine, Karolinska Institute Huddinge, Stockholm, Sweden.
    Antunovic, Petar
    Department of Hematology, Linköping University Hospital, Linköping, Sweden.
    Rangert-Derolf, Åsa
    Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.
    Garelius, Hege K. G.
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Lazarevic, Vladimir Lj J.
    Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.
    Myhr-Eriksson, Kristina
    Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Möllgård, Lars
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Uggla, Bertil
    Örebro University, School of Medical Sciences. Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Wåhlin, Anders C. E.
    Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Wennström, Lovisa
    Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Höglund, Martin
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Juliusson, Gunnar J.
    Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.
    Early death rates remain high in high-risk APL: update from the Swedish Acute Leukemia Registry 1997-20132017In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 6, p. 1457-1459Article in journal (Refereed)
  • 11.
    Mulligan, Stephen P
    et al.
    Department of Haematology, Royal North Shore Hospital, St LeonardsSydney, NSW, Australia .
    Karlsson, Karin
    Department of Hematology, University Hospital, Linköping, Sweden; Department of Hematology, Skåne University Hospital, Lund, Sweden .
    Strömberg, Mats
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden .
    Jønsson, Viggo
    Department of Hematology, National Hospital, Copenhagen, Denmark .
    Gill, Devinder
    Department of Haematology, Princess Alexandra Hospital, Brisbane, Australia.
    Hammerström, Jens
    Department of Hematology, St Olav University Hospital, Trondheim, Norway .
    Hertzberg, Mark
    Department of Haematology, Westmead Hospital, Sydney, Australia .
    McLennan, Roger
    Department of Haematology, Ballarat Base Hospital, Ballarat, Australia .
    Uggla, Bertil
    Örebro University Hospital. Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Norman, John
    Department of Haematology, Royal Adelaide Hospital, Adelaide, Australia .
    Wallvik, Jonas
    Department of Medicine, Region Västernorrland County Hospital, Sundsvall, Sweden .
    Sundström, Gunnel
    Department of Hematology, Norrlands University Hospital, Umeå, Sweden .
    Johansson, Hemming
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden .
    Brandberg, Yvonne
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden .
    Liliemark, Jan
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden; Swedish Council on Health Technology Assessment, Stockholm, Sweden .
    Juliusson, Gunnar
    Department of Hematology, University Hospital, Linköping, Sweden; Department of Hematology, Skåne University Hospital, Lund, Sweden .
    Cladribine prolongs progression-free survival and time to second treatment compared to fludarabine and high-dose chlorambucil in chronic lymphocytic leukemia2014In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 55, no 12, p. 2769-2777Article in journal (Refereed)
    Abstract [en]

    We conducted a randomized phase III trial to compare the efficacy and safety of two purine analogs, cladribine and fludarabine, with high-dose chlorambucil, in patients with previously untreated chronic lymphocytic leukemia (CLL). Between 1997 and 2004, 223 patients with CLL were randomly assigned to cladribine, fludarabine or chlorambucil, for six cycles of therapy with frequent health-related quality of life assessments. There was no statistical difference for the primary endpoint of overall response with cladribine (70%), fludarabine (67%) and chlorambucil (59%), or complete remission (12%, 7% and 8%), respectively. However, the median progression-free survival (25, 10, 9 months) and median time to second treatment (40, 22, 21 months) were superior with cladribine. There was no significant difference in overall survival (96, 82 and 91 months), nor in toxicity or HRQoL assessments. Monotherapy with cladribine gives superior PFS and longer response duration than fludarabine and chlorambucil as first-line treatment of CLL.

  • 12.
    Prenkert, Malin
    et al.
    Örebro University, School of Health and Medical Sciences.
    Uggla, Bertil
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences.
    Strid, Hilja
    CRIM1 is expressed at higher levels in drug resistant than in drug sensitive myeloid leukemia HL60 cellsManuscript (preprint) (Other academic)
  • 13.
    Prenkert, Malin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Research Center, Örebro University Hospital, Örebro; Sweden.
    Uggla, Bertil
    Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Strid, Hilja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    CRIM1 is expressed at higher levels in drug-resistant than in drug-sensitive myeloid leukemia HL60 cells2010In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 30, no 10, p. 4157-61Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to explore possible differences in the mRNA expression levels of CRIM1, SMAD5, BMP4 and BMP7 in sensitive (S) and multidrug-resistant (R0.5) myeloid leukemia HL60 cells.

    Materials and Methods: HL60S and HL60R0.5 cells were exposed to daunorubicin (DNR) or cytarabine (Ara-C).

    Results: Baseline levels of CRIM1 were found to be 15-fold higher in HL60R0.5 than in HL60S. Sixteen hours of exposure to DNR resulted in a 5.6-fold increase in CRIM1 levels in HL60S. Exposure to either DNR or Ara-C resulted in modest increases in CRIM1 levels in HL60R0.5. Similarly, baseline levels of SMAD5 and BMP4 were higher in HL60R0.5 than in HL60S cells. Analysis of the drug SMAD5-resistance marker permeability-glycoprotein (Pgp) revealed that CRIM1 and Pgp exhibit a covariance pattern of expression.

    Conclusion: This study demonstrated that CRIM1 is expressed at high levels in resistant leukemia cells, indicating that CRIM1 may play a role in drug-resistance.

  • 14.
    Prenkert, Malin
    et al.
    Örebro University, School of Health and Medical Sciences.
    Uggla, Bertil
    Karolinska Institutet.
    Tina, Elisabet
    Örebro University, School of Health and Medical Sciences.
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences.
    Strid, Hilja
    Örebro University, School of Health and Medical Sciences.
    Rapid Induction of P-Glycoprotein mRNA and Protein Expression by Cytarabine in HL-60 Cells2009In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 29, no 10, p. 4071-4076Article in journal (Refereed)
    Abstract [en]

    Background: Overexpression of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and glutathione-S-transferase π (GSTπ) is associated with drug resistance in acute myeloid leukemia (AML). The short-term effects of drug exposure on their expression levels were investigated.

    Materials and Methods: HL-60 cells and drug-resistant sublines were cultured with or without daunorubicin (DNR) and cytarabine (Ara-C). At several time-points the expression levels of P-gp, BCRP and GSTπ were determined.

    Results: After exposure to Ara-C, P-gp mRNA rapidly increased in all the cell lines. P-gp protein was detected in the sensitive cells after 8 h exposure to Ara-C. GSTπ mRNA increased in the resistant cells, but no change in BCRP mRNA was observed. Exposure to DNR revealed rapidly increased P-gp and GSTπ mRNA in the resistant cells.

    Conclusion: Ara-C rapidly increases P-gp mRNA and protein expression in sensitive and resistant cells, and GSTπ mRNA in resistant cells, in vitro. This may be of clinical importance during AML induction chemotherapy.

  • 15.
    Uggla, Bertil
    et al.
    Department of Medicine, Örebro Medical Center Hospital, Örebro, Sweden.
    Möllgård, Lars
    Department of Hematology, Huddinge Uniersity Hospital, Huddinge, Sweden.
    Ståhl, Elisabeth
    Department of Pathology, Örebro Medical Center Hospital, Örebro, Sweden.
    Mossberg, Lise-Lott Mossberg
    Department of Pathology, Örebro Medical Center Hospital, Örebro, Sweden.
    Karlsson, Mats G.
    Department of Pathology, Örebro Medical Center Hospital, Örebro, Sweden.
    Paul, Christer
    Department of Pathology, Örebro Medical Center Hospital, Örebro, Sweden; Karolinska Institute, Stockholm, Sweden.
    Tidefelt, Ulf
    Department of Medicine, Örebro Medical Center Hospital, Örebro, Sweden; Karolinska Institute, Stockholm, Sweden.
    Expression of topoisomerase IIalpha in the G0/G1 cell cycle phase of fresh leukemic cells2001In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 25, no 11, p. 961-966Article in journal (Refereed)
    Abstract [en]

    Topoisomerase IIalpha (topoII alpha) is the target enzyme for several antineoplastic drugs. Correlation between low expression of topo IIalpha and drug resistance has been shown in vitro, but there is limited evidence of a correlation to initial response to treatment or to overall prognosis. Normal cells express topo IIalpha in S/G2/M phase of the cell cycle but not in G0/G1 phase. However, some data suggest that topo IIalpha could be expressed in G0/G1 phase in malignant cells. We have investigated the expression of topo IIalpha in leukemic cells from 25 patients with acute leukemia by flow cytometry, separating cells of different cell cycle phases. We demonstrated that 9/25 samples showed >50% positive cells in G0/G1, and another five samples showed >20%. This finding could possibly provide an explanation to previous difficulties in correlating topo IIalpha expression with clinical outcome. Six of eight patients, where >20% of the cells in G0/G1 were positive for topo IIalpha, entered CR, compared to one of five patients with <20% topo IIalpha positive cells in G0/G1. We suggest that topo IIalpha expression in G0/G1 in leukemic cells may be of predictive value for clinical response to cytostatic drugs.

  • 16.
    Uggla, Bertil
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden.
    Nilsson, Torbjörn
    Department of Medical Biosciences/Clinical Chemistry, Umeå University, Umeå, Sweden.
    Whole blood viscosity in plasma cell dyscrasias2015In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, no 3, p. 122-124Article in journal (Refereed)
    Abstract [en]

    Objectives: Plasma or serum hyperviscosity in plasma cell dyscrasias (PCD) has been described as a risk factor for circulatory disturbances. Whole blood viscosity (WBV) would theoretically be a better biomarker but has not been studied in PCD.

    Design and methods: Plasma viscosity (PV) and WBV were measured in 89 subjects with PCD and in 60 healthy blood donors by free oscillation rheometry. A complete blood count was obtained using an automated hematology analyzer. Plasma proteins were quantitated by immunoturbidimetry.

    Results: The reference intervals for men & women were 1.16-1.36 & 1.16-1.38. mPa for PV, and 4.9-6.3 & 4.4-6.2. mPa for WBV, respectively. Of the PCD patients, 71% had PV above the reference limit and 40% were above the WBV limit. Multivariate analysis showed that WBV was independently related to hematocrit, PV, concentration of the monoclonal protein (M-protein), plasma fibrinogen concentration and albumin concentration. This model accounted for 76% of the variance in WBV. When the same model was applied to PV, only the concentration of the M-protein was significantly related and the model accounted only for 20% of the variance in PV.

    Conclusion: PV cannot be used as a surrogate marker for WBV in PCD patients. Whole blood viscosity should replace plasma viscosity in patients with PCD.

  • 17.
    Uggla, Bertil
    et al.
    Department of Medicine, Örebro University Hospital, Örebro; Karolinska Institute, Stockholm.
    Ståhl, Elisabet
    Clinical Research Centre, Örebro University Hospital, Örebro.
    Wågsäter, Dick
    Örebro University, Department of Nursing and Caring Sciences.
    Paul, Christer
    Department of Haematology, Huddinge University Hospital, Stockholm; Karolinska Institute, Stockholm.
    Karlsson, Mats G.
    Department of Pathology, Örebro University Hospital, Örebro.
    Sirsjö, Allan
    Örebro University, Department of Nursing and Caring Sciences.
    Tidefelt, Ulf
    Örebro University, Department of Clinical Medicine. Department of Medicine, Örebro University Hospital, Örebro.
    BCRP mRNA expression v. clinical outcome in 40 adult AML patients2005In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 29, no 2, p. 141-146Article in journal (Refereed)
    Abstract [en]

    Efflux pumps are considered being mechanisms behind drug resistance in acute myeloid leukaemia (AML). A recently described efflux pump, breast cancer resistance protein (BCRP), can be expressed in AML, but its clinical importance is uncertain. In this study BCRP mRNA expression was determined in samples from 40 AML patients by real-time RT-PCR. The expression varied from negative to 76 times that of control cells. There was no difference in BCRP mRNA expression between patients responding to induction treatment and non-responders. However, in the group of responders, the 14 patients with the highest expression had significantly shorter overall survival (mean 38 months, SEM 15 months) than the 14 patients with the lowest (74 months, SEM 16 months) (P = 0.047). This suggests a possible role of BCRP in drug resistance in AML.

  • 18.
    Uggla, Bertil
    et al.
    Department of Medicine, Örebro University Hospital, Örebro.
    Tina, Elisabet
    Clinical Research Centre, Örebro University Hospital, Örebro.
    Nahi, Hareth
    Department of Clinical Hematology, Karolinska University Hospital, Huddinge, Stockholm; Karolinska Institute, Stockholm.
    Paul, Christer
    Department of Clinical Hematology, Karolinska University Hospital, Huddinge, Stockholm; Karolinska Institute, Stockholm.
    Höglund, Martin
    Department of Haematology, Uppsala University Hospital, Uppsala,.
    Sirsjö, Allan
    Örebro University, Department of Clinical Medicine.
    Tidefelt, Ulf
    Örebro University, Department of Clinical Medicine. Department of Medicine, Örebro University Hospital, Örebro.
    Topoisomerase IIα mRNA and protein expression vs. in vitro drug resistance and clinical outcome in acute leukaemia2007In: International Journal of Oncology, ISSN 1019-6439, Vol. 31, no 1, p. 153-160Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to correlate the expression of topoisomerase (topo) IIalpha to in vitro drug sensitivity and to the clinical outcome in patients with acute leukaemia. Leukaemic cells were isolated from bone marrow or blood from 94 patients. Topo IIalpha mRNA (n=58) and protein (n=60) expression was determined by real-time RT-PCR and flow cytometry, respectively. In both groups, chemosensitivity testing by a bioluminescence ATP assay was performed to a variable extent for both topo IIalpha poisons and non-topo IIalpha targeting drugs. Topo IIalpha mRNA expression varied with relative values ranging from 0.03 to 14.20 (median 1.10). The median value for topo IIalpha protein-positive cells was 23% (range 0-99%). Cell samples from patients with a high (>median value) percentage of topo IIalpha-positive cells were significantly more sensitive to the topo IIalpha active drugs etoposide and daunorubicin, and showed a borderline value for idarubicin (p=0.08), while there was no difference for non-topo IIalpha targeting drugs. However, we did not find any significant differences in mRNA expression or the percentage of topo IIalpha-positive cells in patients who achieved complete remission after at most two induction courses compared with those who did not, nor did we find any difference in survival when patients with high mRNA expression/percentage of topo IIalpha-positive cells were compared with patients with low values. We conclude that expression of topo IIalpha, determined as percentage of topo IIalpha-positive cells, in leukaemic cells correlates to chemosensitivity in vitro against topoisomerase poisons but that it does not predict clinical outcome in acute leukaemia.

  • 19.
    Vaht, Krista
    et al.
    Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Medicine, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Göransson, Magnus
    Department of Pediatrics, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Carlson, Kristina
    Department of Hematology, Uppsala University Hospital, Uppsala, Sweden.
    Isaksson, Cecilia
    Department of Hematology, Cancer Centre, University Hospital, Umeå, Sweden.
    Lenhoff, Stig
    Department of Hematology, Skåne University Hospital, Lund University, Lund, Sweden.
    Sandstedt, Anna
    Department of Hematology, Linköping University Hospital, Linköping, Sweden.
    Uggla, Bertil
    Örebro University, School of Medical Sciences. Section of Hematology Department of Medicine.
    Winiarski, Jacek
    Astrid Lindgren Children's Hospital, Karolinska University Hospital, Huddinge and CLINTEC, Karolinska Institutet, Stockholm, Sweden.
    Ljungman, Per
    Centre of Allogeneic Stem Cell Transplantation Unit (CAST), Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Per-Ola
    Institute of Medicine, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden; Department of Medicine, Södra Älvsborg Hospital Borås, Borås, Sweden.
    Brune, Mats
    Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Medicine, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    High Graft-versus-Host Disease-Free, Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study2019In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 25, no 10, p. 1970-1974Article in journal (Refereed)
    Abstract [en]

    Allogeneic stem cell transplantation (SCT) as primary treatment for aplastic anemia (AA) is being increasingly used. Yet, age, stem cell source, and donor type are important outcome factors. We have recently performed a nationwide cohort study of all patients with AA in Sweden diagnosed from 2000 to 2011 and now present outcome data on SCT patients. In total, 68 patients underwent SCT, and 63% of them had failed immunosuppressive therapy. We found that, with a median follow-up of 109 months (range, 35 to 192 months), 5-year overall survival (OS) for all patients was 86.8%, whereas graft-versus-host disease-free, relapse/rejection-free survival (GRFS) at 5 years was 69.1%. There was no survival impact regarding the donor type or stem cell source. Patients aged >= 40 years had a higher transplant-related mortality (29.4% versus 7.8%; P= .023), which translated into a lower 5-year OS: 70.6% versus 92.2% (A=.022) and a trend of lower GRFS (52.9% versus 74.5%; P = .069). In conclusion, we found in this real-world setting that both OS and GRFS were high, but SCT for patients with AA aged >= 40 years is problematic, and clinical trials addressing this issue are warranted. (C) 2019 American Society for Transplantation and Cellular Therapy.

  • 20.
    Vaht, Krista
    et al.
    Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden; Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Göransson, Magnus
    Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden; Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Carlson, Kristina
    Department of Hematology, Uppsala University Hospital, Uppsala, Sweden.
    Isaksson, Cecilia
    Department of Hematology, Cancer Centre, University Hospital, Uppsala, Sweden.
    Lenhoff, Stig
    Department of Hematology, Skåne University Hospital, Lund University, Malmö, Sweden.
    Sandstedt, Anna
    Department of Hematology, Linköping University Hospital, Linköping, Sweden.
    Uggla, Bertil
    Örebro University, School of Medical Sciences. Department of Medicine, Section of Hematology, , Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Winiarski, Jacek
    Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Ljungman, Per
    Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Brune, Mats
    Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden; Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Andersson, Per-Ola
    South Älvsborg Hospital, Borås, Sweden; Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Incidence and outcome of acquired aplastic anemia: real-world data from patients diagnosed in Sweden from 2000-20112017In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, no 10, p. 1683-1690Article in journal (Refereed)
    Abstract [en]

    A plastic anemia is a rare life-threatening disease. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, the outcome has improved considerably, and the 5-year survival is reported to be 70-80% in selected patient cohorts. Yet, contemporary population-based data on incidence and survival are lacking. We performed a national retrospective study to determine the incidence, treatment, and survival of patients with aplastic anemia diagnosed in Sweden from 2000-2011. Patients were included via the National Patient Registry, and diagnosed according to the Camitta criteria. In total, 257 confirmed cases were identified, with an overall incidence of 2.35 (95% CI: 2.06-2.64) cases per million inhabitants per year. Median age was 60 years (range: 2-92), and median follow up was 76 (0-193) months. Primary treatments included immunosuppressive therapy (63%), allogenic stem cell transplantation (10%), or single-agent cyclosporine/no specific therapy (27%). The 5-year survival was 90.7% in patients aged 0-18 years, 90.5% in patients aged 19-39 years, 70.7% in patients aged 40-59 years, and 38.1% in patients aged ≥60 years. Multivariate analysis showed that age (both 40-59 and ≥60 age groups), very severe aplastic anemia and single-agent cyclosporine/no specific therapy were independent risk factors for inferior survival. In conclusion, younger aplastic anemia patients experience a very good long-term survival, while that of patients ≥60 years in particular remains poor. Apparently, the challenge today is to improve the management of older aplastic anemia patients, and prospective studies to address this medical need are warranted.

  • 21.
    Vaht, Krista
    et al.
    Section of Haematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Medicine, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Göransson, Magnus
    Department of Pediatrics, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Carlson, Kristina
    Department of Haematology, Uppsala University Hospital, Uppsala, Sweden.
    Isaksson, Cecilia
    Department of Haematology, Cancer Centre, University Hospital, Umeå, Sweden.
    Lenhoff, Stig
    Department of Haematology, Skåne University Hospital, Lund University, Lund, Sweden.
    Sandstedt, Anna
    Department of Haematology, Linköping University Hospital, Linköping, Sweden.
    Uggla, Bertil
    Örebro University, School of Medical Sciences. Section of Haematology Department of Medicine.
    Winiarski, Jacek
    Astrid Lindgren Children's Hospital, Karolinska Institutet, Karolinska University Hospital and CLINTEC, Stockholm, Sweden.
    Ljungman, Per
    Centre of Allogeneic Stem Cell Transplantation Unit (CAST), Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Brune, Mats
    Section of Haematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Medicine, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Andersson, Per-Ola
    Institute of Medicine, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden; Department of Medicine, Södra Älvsborg Hospital Borås, Borås, Sweden.
    Low response rate to ATG-based immunosuppressive therapy in very severe aplastic anaemia: A Swedish nationwide cohort study2018In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 100, no 6, p. 613-620Article in journal (Refereed)
    Abstract [en]

    Objectives: Antithymocyte globulin (ATG)-based immunosuppression remains a cornerstone in aplastic anaemia (AA) treatment. However, most ATG studies are not population-based and knowledge about real-world results concerning response and outcome could offer important information for treating physicians.

    Methods: We have recently performed a nationwide retrospective cohort study on all AA patients diagnosed in Sweden in 2000–2011 and now present treatment and outcome data on patients receiving first-line ATG. In total, 158 patients showed a 47.0% response rate which was similar in all age groups (range 41.5%-51.7%) with no difference regarding ATG formulation. The response was significantly associated with severity grade—especially at time of treatment initiation: very severe (VSAA) 22.7%; severe (SAA) 54.5% (P <.001); and non-severe 88.5% (P <.001). A logistic regression-based predictive model indicated that VSAA patients with an absolute reticulocyte count <25 × 109/L had only a 19% probability of response. In a multivariable analysis, age and VSAA at the time of treatment were the independent factors for inferior survival.

    Conclusions: Real-world VSAA patients respond poorly to ATG which indicates the need for a different treatment approach. Our findings suggest that age alone should not be a discriminating factor for administering ATG treatment.

  • 22.
    Österroos, Albin
    et al.
    Uppsala University Hospital, Uppsala, Sweden.
    Eriksson, Anna
    Uppsala University Hospital, Uppsala, Sweden.
    Antunovic, Petar
    Linköping University Hospital, Linköping, Sweden.
    Cammenga, Jörg
    Linköping University, Linköping, Sweden.
    Deneberg, Stefan
    Karolinska University Hospital, Stockholm, Sweden.
    Lazarevic, Vladimir
    Skåne University Hospital, Lund, Sweden.
    Lorenz, Fryderyk
    Umeå University, Umeå, Sweden.
    Möllgård, Lars
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Derolf, Åsa R.
    Karolinska Institute, Stockholm, Sweden.
    Uggla, Bertil
    Örebro University, School of Medical Sciences.
    Wennström, Lovisa
    Sahlgrenska Academy, Gothenburg, Sweden.
    Ölander, Emma
    Sundsvall Hospital, Sundsvall, Sweden.
    Höglund, Martin
    Uppsala University Hospital, Uppsala, Sweden.
    Juliusson, Gunnar
    Sundsvall Hospital, Sundsvall, Sweden.
    Lehmann, Sören
    Uppsala University Hospital, Uppsala, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Real-world data on treatment patterns and outcomes of hypomethylating therapy in patients with newly diagnosed acute myeloid leukaemia aged ≥ 60 years2020In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 189, no 1, p. e13-e16Article in journal (Refereed)
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