BACKGROUND: Primary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT) in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML. METHODS: The current study aimed to address the issue of HSCT for PRF-AML and to compare the outcomes of HSCT from matched sibling donors (n = 660) versus unrelated donors (n = 381), for patients with PRF-AML between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. RESULTS: HSCT provide patients with PRF-AML a 2-year leukemia-free survival and overall survival of about 25 and 30%, respectively. In multivariate analysis, two predictive factors, cytogenetics and time from diagnosis to transplant, were associated with lower leukemia-free survival, whereas Karnofsky performance status at transplant ≥90% was associated with better leukemia-free survival (LFS). Concerning relapse incidence, cytogenetics and time from diagnosis to transplant were associated with increased relapse. Reduced intensity conditioning regimen was the only factor associated with lower non-relapse mortality. CONCLUSIONS: HSCT was able to rescue about one quarter of the patients with PRF-AML. The donor type did not have any impact on PRF patients' outcomes. In contrast, time to transplant was a major prognostic factor for LFS. For patients with PRF-AML who do not have a matched sibling donor, HSCT from an unrelated donor is a suitable option, and therefore, initiation of an early search for allocating a suitable donor is indicated.

Acute Leukemia Working Party Office Hôpital Saint Antoine APHP Paris France

Bone Marrow Transplantation Center University Hospital Eppendorf Hamburg Germany

Chaim Sheba Medical Center Tel Hashomer Israel

Charite Campus Benjamin Franklin Universitaetsmedizin Berlin Klinik 3 Hematologie u Onkologie Hindenburgdamm Berlin Germany

Department of Clinical Hematology Institute of Hematology and Blood Transfusion Prague Czech Republic

Department of Haematology Oncology University Hospital Regensburg Regensburg Germany

Department of Hematology Hemostasis Oncology and Stem Cell Transplantation Hannover Medical School Hannover Germany

Department of Internal Medicine 1 Bone Marrow Transplantation Unit Medical University of Vienna Vienna Austria

Department of Internal Medicine 2 Würzburg University Medical Center Würzburg Germany

Department of Medicine A Hematology and Oncology University of Muenster Muenster Germany

Department of Stem Cell Transplantation University Medical Center Hamburg Eppendorf Hamburg Germany

Deutsche Klinik für Diagnostik KMY Zentrum Wiesbaden Germany

Division of Stem Cell Transplantation and Immunotherapy University of Kiel Kiel Germany

Faculty of Medicine and Medical Center Hematology Oncology and Stem Cell Transplantation University of Freiburg Freiburg im Breisgau Germany

Hematology CHU de Bordeaux Bordeaux France

Hospital Clinic Institut d'investigacions Biomèdiques August Pi i Sunyer Barcelona Spain

Klinik fuer Innere Medizin 3 Universtätklinikum Ulm Germany

Klinikum Grosshadern Med Klinik 3 München Germany

Medical Department Hematology and Oncology University of Tuebingen Tübingen Germany

Medizinische Klinik Klinikum Augsburg Germany

Medizinische Klinik und Poliklinik 1 Universitätsklinikum Dresden Germany

Medizische Klinik Paracelsus Medizinische Privatuniversität Nürnberg Germany

Service d'Hématologie Clinique et de Thérapie Cellulaire Hôpital Saint Antoine APHP 184 rue du faubourg Saint Antoine 75571 Paris Cedex 12 France

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