title: The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years-a report from the EBMT acute leukemia working party.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Hematology, Hôpital Brabois, CHRU Nancy, Vandœuvre-lès-Nancy, France. mt_rubio@hotmail.com.|CNRS UMR 7365, IMoPA, Nancy, France. mt_rubio@hotmail.com.|Université de Lorraine, Nancy, France. mt_rubio@hotmail.com.|Acute Leukemia Working Party of EBMT, Paris, France. mt_rubio@hotmail.com.
authors.forename: Marie T
authors.initials: MT
authors.lastname: Rubio
authors.affiliation: Acute Leukemia Working Party of EBMT, Paris, France. Bipin.Savani@Vanderbilt.Edu.|Vanderbilt University Medical Center, Nashville, TN, USA. Bipin.Savani@Vanderbilt.Edu.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: Acute Leukemia Working Party of EBMT, Paris, France.|EBMT Paris study office/CEREST-TC, Paris, France.|Department of Haematology, Saint Antoine Hospital, Paris, France.|INSERM UMR 938, Paris, France.|Université Pierre et Marie Curie, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: Acute Leukemia Working Party of EBMT, Paris, France.|EBMT Paris study office/CEREST-TC, Paris, France.|Department of Haematology, Saint Antoine Hospital, Paris, France.|INSERM UMR 938, Paris, France.|Université Pierre et Marie Curie, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Polge
authors.affiliation: Division Hematology, Oncology and Hemostasiology, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.affiliation: Department of Haematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.affiliation: Deutsche KlinikfürDiagnostik, KMT Zentrum, Wiesbaden, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Schwerdtfeger
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: Department of Medicine, Hematology, Oncology, University of Freiburg, Freiburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Finke
authors.affiliation: MedizinischeKlinik m. S. Hämatologie/Onkologie, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Arnold
authors.initials: A
authors.lastname: Renate
authors.affiliation: Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Craddock
authors.affiliation: Department of Stem cell Transplantation, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.affiliation: Department of Medicine, University of Cologne, Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.affiliation: Department of Hematology/Oncology, Charles University Hospital, Pilsen, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Jindra
authors.affiliation: Acute Leukemia Working Party of EBMT, Paris, France.|EBMT Paris study office/CEREST-TC, Paris, France.|Department of Haematology, Saint Antoine Hospital, Paris, France.|INSERM UMR 938, Paris, France.|Université Pierre et Marie Curie, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Acute Leukemia Working Party of EBMT, Paris, France.|Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000368:Aged; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D061349:Unrelated Donors
keywords: Acute leukemia; Allogeneic stem cell transplantation; Anti-leukemic effect; HLA matching; Older patients; Toxicity; Unrelated donor