BACKGROUND: Data comparing fully matched and mismatched-unrelated-donor (M- and mM-URD) allogeneic hematopoietic stem cell transplant (allo-SCT) following reduced intensity conditioning regimens for acute myeloid leukemia are limited. METHODS: We retrospectively compared the outcome of 3398 patients above the age of 50 years who underwent 10/10 M-URD (n = 2567), 9/10 (n = 723), or 8/10 (n = 108) mM-URD allo-SCT for acute myeloid leukemia after reduced intensity conditioning regimen between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. RESULTS: HLA matching had no impact on engraftment (p = 0.31). In univariate analysis, in comparison to 10/10 M-URD, mM-URD was associated with higher incidence of grade II-IV acute graft-versus-host disease (GVHD) (p = 0.0002), similar rates of chronic GVHD (p = 0.138) but increased incidence of its extensive form (p = 0.047). Compared to 10/10 M-URD, patients transplanted in the first complete remission (CR1) with a 9 or an 8/10 mM-URD had decreased 2-year leukemia free (LFS) (p = 0.005) and overall survivals (OS) (56.7, 46.1, and 50.2 %, respectively, p = 0.005), while outcomes were comparable between all groups for patients transplanted beyond CR1. In multivariate analysis, 9/10 versus 10/10 URD was associated with higher non-relapse mortality (HR 1.34, p = 0.001), similar risk of relapse and chronic GVHD and inferior LFS (HR 1.25, p = 0.0001), and OS (HR 1.27, p = 0.0001). There was no difference in adjusted transplant outcomes between 9/10 and 8/10 mM-URD. CONCLUSIONS: Reduced intensity conditioned allo-SCT with a 10/10 M-URD remains the preferable option for AML patients above the age of 50 years. The use of a 9/10 or an 8/10 mM-URD in patients not having a fully matched donor represents an alternative therapeutic option that should be compared to other alternative donor transplant strategies.

Acute Leukemia Working Party of EBMT Paris France

Centre for Clinical Haematology Queen Elizabeth Hospital Birmingham UK

CNRS UMR 7365 IMoPA Nancy France

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

Department of Haematology Saint Antoine Hospital Paris France

Department of Hematology Hôpital Brabois CHRU Nancy Vandœuvre lès Nancy France

Department of Hematology Oncology Charles University Hospital Pilsen Czech Republic

Department of Medicine Hematology Oncology University of Freiburg Freiburg Germany

Department of Medicine University of Cologne Cologne Germany

Department of Stem cell Transplantation University Hospital Eppendorf Hamburg Germany

Deutsche KlinikfürDiagnostik KMT Zentrum Wiesbaden Germany

Division Hematology Oncology and Hemostasiology University Hospital Leipzig Leipzig Germany

EBMT Paris study office CEREST TC Paris France

Hematology Division Chaim Sheba Medical Center Tel Hashomer Ramat Gan Israel

INSERM UMR 938 Paris France

Medizinische Klinik und Poliklinik 1 Universitätsklinikum Carl Gustav Carus der TU Dresden Dresden Germany

MedizinischeKlinik m S Hämatologie Onkologie Campus Virchow Klinikum Charité Universitätsmedizin Berlin Berlin Germany

Université de Lorraine Nancy France

Université Pierre et Marie Curie Paris France

Vanderbilt University Medical Center Nashville TN USA

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