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  • 1.
    Burman, Joachim
    et al.
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Iacobaeus, Ellen
    Karolinska Institute Solna, Sweden.
    Svenningsson, Anders
    Umeå University, Sweden; University Hospital Northern Sweden, Sweden.
    Lycke, Jan
    Sahlgrens University Hospital, Sweden.
    Gunnarsson, Martin
    Örebro University Hospital, Sweden; University of Örebro, Sweden.
    Nilsson, Petra
    Skåne University Hospital Lund, Sweden.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Fredrikson, Sten
    Karolinska Institute Huddinge, Sweden.
    Martin, Claes
    Karolinska Institute, Sweden.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Health Sciences.
    Uggla, Bertil
    University of Örebro, Sweden; Örebro University Hospital, Sweden.
    Lenhoff, Stig
    Skåne University Hospital, Sweden.
    Johansson, Jan-Erik
    Sahlgrens University Hospital, Sweden.
    Isaksson, Cecilia
    Umeå University, Sweden.
    Hagglund, Hans
    University of Uppsala Hospital, Sweden.
    Carlson, Kristina
    University of Uppsala Hospital, Sweden.
    Fagius, Jan
    Uppsala University, Sweden; University of Uppsala Hospital, 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.
    Czerw, Tomasz
    et al.
    Maria Sklodowska Curie Mem Cancer Centre, Poland; Institute Oncol, Poland.
    Labopin, Myriam
    Hop St Antoine, France; INSERM, France; University of Paris 06, France.
    Schmid, Christoph
    University of Munich, Germany.
    Cornelissen, Jan J.
    Erasmus University, Netherlands.
    Chevallier, Patrice
    CHU Nantes, France.
    Blaise, Didier
    Institute J Paoli I Calmettes, France.
    Kuball, Juergen
    University of Medical Centre, Netherlands.
    Vigouroux, Stephane
    Hop Haut Leveque, France.
    Garban, Frederic
    Hop A Michallon, France.
    Lioure, Bruno
    Nouvel Hop Civil, France.
    Fegueux, Nathalie
    CHU Lapeyronie, France.
    Clement, Laurence
    Centre Hospital University of CHU Nancy, France.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Maertens, Johan
    University Hospital Gasthuisberg, Belgium.
    Guillerm, Gaelle
    CHU Morvan, France.
    Bordessoule, Dominique
    CHRU Limoges, France.
    Mohty, Mohamad
    Hop St Antoine, France; INSERM, France; University of Paris 06, France.
    Nagler, Arnon
    Hop St Antoine, France; Chaim Sheba Medical Centre, Israel.
    High CD3+and CD34+peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia - an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 19, p. 27255-27266Article in journal (Refereed)
    Abstract [en]

    Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, amp;gt;347 x 10amp;lt;^amp;gt;6/kg and amp;gt;8.25 x 10amp;lt;^amp;gt;6/kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95% CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes.

  • 3.
    Eketorp Sylvan, Sandra
    et al.
    Karolinska Inst, Sweden.
    Asklid, Anna
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Johansson, Hemming
    Karolinska Inst, Sweden.
    Klintman, Jenny
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Bjellvi, Jenny
    Sahlgrens Univ Hosp, Sweden.
    Tolvgard, Staffan
    Ostersunds Hosp, Sweden.
    Kimby, Eva
    Karolinska Inst, Sweden.
    Norin, Stefan
    Karolinska Inst, Sweden.
    Andersson, Per-Ola
    South Alvsborg Hosp, Sweden.
    Karlsson, Claes
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Karlsson, Karin
    Skane Univ Hosp, Sweden.
    Lauri, Birgitta
    Sunderby Hosp, Sweden.
    Mattsson, Mattias
    Uppsala Univ Hosp, Sweden.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Strandberg, Maria
    Sundsvall Hosp, Sweden.
    Osterborg, Anders
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Hansson, Lotta
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    FFirst-line therapy in chronic lymphocytic leukemia: a Swedish nation-wide real-world study on 1053 consecutive patients treated between 2007 and 20132019In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 104, no 4, p. 797-805Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate long-term outcome following first-line therapy in consecutive chronic lymphocytic leukemia (CLL) patients in a well-defined geographic area: Sweden. All patients diagnosed with CLL (2007-2013) (n=3672) were identified from national registries, screening of patient files identified all (100%) treated first line (n=1053) and for those, an in-depth analysis was performed. End points were overall response rate, progression-free survival (PFS), overall survival (OS), and safety. Median age was 71 years; 53% had Rai stage III-IV and 97% had performance status grade 0-2. Fluorescence in situ hybridization (FISH) was performed in 57% of patients: 15% had del(17p). Chlorambucil + prednisone was used in 39% (5% also received rituximab). Fludarabine+cyclophosphamide+rituximab or fludarabine+cyclophosphamide was used in 43% and bendamustine + rituximab in 6%. Overall response rate was 64%; chlorambucil 43%, fludarabine+cyclophosphamide+rituximab 84%, fludarabine+cyclophosphamide 75% and bendamustine + rituximab 75%. Median PFS and OS was 24 and 58 months, respectively, both were significantly associated (multivariate analysis) with type of treatment, del(17p), performance status, gender, age and geographical region (OS only). Chlorambucil-treated patients had a median PFS and OS of only 9 and 33 months, respectively. Chlorambucil usage declined gradually throughout the study period, but one-third of patients still received chlorambucil + rituximab in 2013. Infections amp;gt;= grade III were significantly associated with treatment; chlorambucil 19% versus fludarabine+cyclophosphamide+rituximab 30%. Richter transformation occurred in 5.5% of the patients, equally distributed across therapies. This is the largest retrospective, real-world cohort of consecutive first-line treated CLL patients with a complete follow up. In elderly patients, an unmet need for more effective, well-tolerated therapies was identified.

  • 4.
    Håkansson, Irene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Lundin, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Askmark, Håkan
    University of Uppsala Hospital, Sweden.
    Pirskanen, Ritva
    Karolinska Institute, Sweden.
    Carlson, Kristina
    University Hospital, Sweden.
    Piehl, Fredrik
    Karolinska Institute, Sweden.
    Hägglund, Hans
    University Hospital, Sweden.
    Successful autologous haematopoietic stem cell transplantation for refractory myasthenia gravis - a case report2017In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 27, no 1, p. 90-93Article in journal (Refereed)
    Abstract [en]

    Myasthenia gravis (MG) is an autoimmune disease, with immune reactivity against the post-synaptic endplate of the neuromuscular junction. Apart from symptomatic treatment with choline esterase blockers, many patients also require immunomodulatory treatment. Despite existing treatment options, some patients are treatment refractory. We describe a patient with severe MG refractory to corticosteroids, four oral immunosuppressants, cyclophosphamide, rituximab and bortezomib who was treated with autologous haematopoietic stem cell transplantation. Two years after this, the patient has significantly improved in objective tests and in quality of life and leads an active life. Diplopia is her only remaining symptom and she is completely free of medication for MG. We believe that autologous haematopoietic stem cell transplantation can be an effective therapeutic option for carefully selected cases of severe, treatment refractory MG. (c) 2016 Elsevier B.V. All rights reserved.

  • 5.
    Pahnke, Simon
    et al.
    Uppsala Univ Hosp, Sweden; Uppsala Univ, Sweden.
    Larfors, Gunnar
    Uppsala Univ Hosp, Sweden.
    Axdorph-Nygell, Ulla
    Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Fischer-Nielsen, Anne
    Copenhagen Univ Hosp, Denmark.
    Haastrup, Eva
    Copenhagen Univ Hosp, Denmark.
    Heldal, Dag
    Oslo Univ Hosp, Norway.
    Itala-Remes, Maija
    Turku Univ Hosp, Finland.
    Johansson, Jan-Erik
    Univ Gothenburg, Sweden.
    Kauppila, Marjut
    Turku Univ Hosp, Finland.
    Lenhoff, Stig
    Skane Univ Hosp, Sweden.
    Ljungman, Per
    Karolinska Inst, Sweden; Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Niittyvuopio, Riita
    Helsinki Univ Hosp, Finland.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Hagglund, Hans
    Uppsala Univ Hosp, Sweden.
    Short-term side effects and attitudes towards second donation: A comparison of related and unrelated haematopoietic stem cell donors2018In: Journal of clinical apheresis, ISSN 0733-2459, E-ISSN 1098-1101, Vol. 33, no 3, p. 226-235Article in journal (Refereed)
    Abstract [en]

    The Nordic Register of Haematopoietic Stem Cell Donors (NRHSD) has registered related and unrelated donors from 10 transplant centres in Sweden, Norway, Finland and Denmark since 1998. We present a prospective, observational study of 1,957 donors, focusing mainly on the differences between related and unrelated donors. Related donors are reported to have more comorbidities, but similar side effects compared with unrelated donors. Side effects after BM or PBSC donation are generally of short duration and in this study no deaths, myocardial infarctions, splenic ruptures, or thromboembolic events are reported. Interestingly, related donors express more hesitancy towards donating again when asked 1 month after donation.

  • 6.
    Skoglund, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Richter, J.
    Department of Hematology and Coagulation, Skåne University Hospital, Lund, Sweden.
    Olsson-Strömberg, U.
    Department of Medical Sciences, Uppsala University and Department of Hematology, University Hospital, Uppsala, Sweden.
    Bergquist, J.
    Analytical Chemistry, Department of Chemistry – Biomedical Center and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Aluthgedara, W.
    Analytical Chemistry, Department of Chemistry – Biomedical Center and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Ubhayasekera, K.
    Analytical Chemistry, Department of Chemistry – Biomedical Center and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Svedberg, A.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Söderlund, S.
    Department of Medical Sciences, Uppsala University and Department of Hematology, University Hospital, Uppsala, Sweden.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Health Sciences.
    Johnsson, A.
    Department of Internal Medicine, Motala Hospital, Motala, Sweden.
    Aagesen, J.
    Department of Medicine, Ryhov County Hospital, Jönköping, Sweden.
    Alsenhed, J.
    Department of Internal Medicine, Västervik Hospital, Västervik, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    In vivo CYP3A activity and pharmacokinetics of imatinib in relation to therapeutic outcome in chronic myeloid leukemia patientsManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: The hepatic enzymes CYP3A4 and CYP3A5 metabolize the tyrosine kinase inhibitor imatinib into a large number of metabolites including the pharmacologically active N-desmethyl imatinib (CGP74588). Because the metabolic activity of CYP3A varies considerably between individuals and a previous pilot study suggested an inverse association between in vivo CYP3A metabolic activity and therapeutic outcome of imatinib, the primary aim of this study was to investigate the influence of CYP3A metabolic activity on the outcome of imatinib therapy in chronic myeloid leukemia patients.

    Methods: Fifty-five patients were included and CYP3A activity was estimated in vivo using quinine as a probe drug. Imatinib and CGP74588 trough concentrations in the plasma were determined at steady state in 34 patients. Cytogenetic and molecular responses after 12 months of first-line imatinib were retrospectively collected from patients’ medical records.

    Results: Patients with optimal response to imatinib (complete cytogenetic response (CCgR) or molecular response of BCR-ABL <1%) did not have different levels of CYP3A activity compared to non-optimal responders. Similar results were found when analyzing the molecular response and CCgR separately. Neither the imatinib trough concentration nor the CGP74588/imatinib ratio were significantly associated with CYP3A activity.

    Conclusion: CYP3A enzyme activity, as measured by quinine metabolic ratio, does not correlate with the plasma concentrations of imatinib or CGP74588 and is not predictive of imatinib therapeutic outcome. These results indicate that even though imatinib is metabolized by CYP3A enzymes, this activity is not the   ratelimiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes such as plasma protein binding or transport protein activity to look for the major contributor to patient variability in imatinib plasma concentration.

  • 7.
    Skoglund, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Richter, Johan
    Skåne University Hospital, Sweden.
    Olsson-Stromberg, Ulla
    Uppsala University, Sweden.
    Bergquist, Jonas
    Uppsala University, Sweden.
    Aluthgedara, Warunika
    Uppsala University, Sweden.
    Ubhayasekera, S. J. Kumari A.
    Uppsala University, Sweden.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Svedberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Söderlund, Stina
    Uppsala University, Sweden.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Johnsson, Anders
    Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Aagesen, Jesper
    Ryhov County Hospital, Sweden.
    Alsenhed, Jonas
    Vastervik Hosp, Dept Internal Med, Västervik, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    In Vivo Cytochrome P450 3A Isoenzyme Activity and Pharmacokinetics of Imatinib in Relation to Therapeutic Outcome in Patients With Chronic Myeloid Leukemia2016In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 38, no 2, p. 230-238Article in journal (Refereed)
    Abstract [en]

    Background: Cytochrome P450 3A (CYP3A) isoenzyme metabolic activity varies between individuals and is therefore a possible candidate of influence on the therapeutic outcome of the tyrosine kinase inhibitor imatinib in patients with chronic myeloid leukemia (CML). The aim of this study was to investigate the influence of CYP3A metabolic activity on the plasma concentration and outcome of imatinib in patients with CML. Methods: Forty-three patients with CML were phenotyped for CYP3A activity using quinine as a probe drug and evaluated for clinical response parameters. Plasma concentrations of imatinib and its main metabolite, CGP74588, were determined using liquid chromatography-mass spectrometry. Results: Patients with optimal response to imatinib after 12 months of therapy did not differ in CYP3A activity compared to nonoptimal responders (quinine metabolic ratio of 14.69 and 14.70, respectively; P = 0.966). Neither the imatinib plasma concentration nor the CGP74588/imatinib ratio was significantly associated with CYP3A activity. Conclusions: The CYP3A activity does not influence imatinib plasma concentrations or the therapeutic outcome. These results indicate that although imatinib is metabolized by CYP3A enzymes, this activity is not the rate-limiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes so as to identify the major contributor to patient variability in imatinib plasma concentrations.

  • 8.
    Vaht, Krista
    et al.
    Sahlgrens Univ Hosp, Sweden; Gothenburg Univ, Sweden.
    Goransson, Magnus
    Sahlgrens Univ Hosp, Sweden.
    Carlson, Kristina
    Uppsala Univ Hosp, Sweden.
    Isaksson, Cecilia
    Univ Hosp, Sweden.
    Lenhoff, Stig
    Lund Univ, Sweden.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Uggla, Bertil
    Orebro Univ, Sweden.
    Winiarski, Jacek
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Ljungman, Per
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Andersson, Per-Ola
    Gothenburg Univ, Sweden; Sodra Alvsborg Hosp Boras, Sweden.
    Brune, Mats
    Sahlgrens Univ Hosp, Sweden; Gothenburg Univ, 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 amp;gt;= 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 amp;gt;= 40 years is problematic, and clinical trials addressing this issue are warranted. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

  • 9.
    Vaht, Krista
    et al.
    Sahlgrens University Hospital, Sweden; Gothenburg University, Sweden.
    Goransson, Magnus
    Sahlgrens University Hospital, Sweden.
    Carlson, Kristina
    Uppsala University Hospital, Sweden.
    Isaksson, Cecilia
    University Hospital, Sweden.
    Lenhoff, Stig
    Lund University, Sweden.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Uggla, Bertil
    Örebro University, Sweden.
    Winiarski, Jacek
    Karolinska University Hospital, Sweden.
    Ljungman, Per
    Karolinska University Hospital Huddinge, Sweden.
    Brune, Mats
    Sahlgrens University Hospital, Sweden; Gothenburg University, Sweden.
    Andersson, Per-Ola
    South Alvsborg Hospital Boras, Sweden; Gothenburg University, 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 amp;gt;= 60 years. Multivariate analysis showed that age (both 40-59 and amp;gt;= 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 amp;gt;= 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.

  • 10.
    Vaht, Krista
    et al.
    Sahlgrens Univ Hosp, Sweden; Gothenburg Univ, Sweden.
    Goransson, Magnus
    Sahlgrens Univ Hosp, Sweden.
    Carlson, Kristina
    Uppsala Univ Hosp, Sweden.
    Isaksson, Cecilia
    Univ Hosp, Sweden.
    Lenhoff, Stig
    Lund Univ, Sweden.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology. Linköping University, Faculty of Medicine and Health Sciences.
    Uggla, Bertil
    Orebro Univ, Sweden.
    Winiarski, Jacek
    Karolinska Inst, Sweden; CLINTEC, Sweden.
    Ljungman, Per
    Karolinska Inst, Sweden.
    Brune, Mats
    Sahlgrens Univ Hosp, Sweden; Gothenburg Univ, Sweden.
    Andersson, Per-Ola
    Gothenburg Univ, Sweden; Sodra Alvsborg Hosp Boras, 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]

    ObjectivesAntithymocyte 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. MethodsWe 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 gradeespecially at time of treatment initiation: very severe (VSAA) 22.7%; severe (SAA) 54.5% (Pamp;lt;.001); and non-severe 88.5% (Pamp;lt;.001). A logistic regression-based predictive model indicated that VSAA patients with an absolute reticulocyte count amp;lt;25x10(9)/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. ConclusionsReal-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.

  • 11.
    Winqvist, Maria
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Andersson, Per-Ola
    Boras Hosp, Sweden.
    Asklid, Anna
    Karolinska Inst, Sweden.
    Karlsson, Karin
    Lund Univ Hosp, Sweden.
    Karlsson, Claes
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Lauri, Birgitta
    Sunderby Hosp, Sweden.
    Lundin, Jeanette
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Mattsson, Mattias
    Uppsala Univ Hosp, Sweden.
    Norin, Stefan
    Karolinska Inst, Sweden.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Rosenquist, Richard
    Karolinska Inst, Sweden.
    Spath, Florentin
    Umea Univ, Sweden.
    Hansson, Lotta
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Osterborg, Anders
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Long-term real-world results of ibrutinib therapy in patients with relapsed or refractory chronic lymphocytic leukemia: 30-month follow up of the Swedish compassionate use cohort2019In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 104, no 5, p. E208-E210Article in journal (Other academic)
    Abstract [en]

    n/a

  • 12.
    Winqvist, Maria
    et al.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Asklid, Anna
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Andersson, P. O.
    South Älvsborg Hospital, Sweden.
    Karlsson, Karin
    Skåne University Hospital, Sweden.
    Karlsson, Claes
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Lauri, Birgitta
    Sunderby Hospital, Sweden.
    Lundin, Jeanette
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Mattsson, Mattias
    University of Uppsala Hospital, Sweden.
    Norin, Stefan
    Karolinska University Hospital, Sweden.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology. Linköping University, Faculty of Medicine and Health Sciences.
    Hansson, Lotta
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Osterborg, Anders
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no 12, p. 1573-1580Article in journal (Refereed)
    Abstract [en]

    Ibrutinib, a Brutons tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine healthcare are commonly observed in oncology. Herein we report real-world results for 95 poor prognosis Swedish patients treated with ibrutinib in a compassionate use program. Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015. The median age was 69 years. 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy amp;gt;= 10cm. Patients received ibrutinib 420 mg once daily until progression. At a median follow-up of 10.2 months, the overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression-free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (P=0.017 and P=0.027, log-rank test); no other factor was significant in Cox proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richters transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered in future with regards to new agents and new indications in chronic lymphocytic leukemia.

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