Journal Article

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

Labopin, Myriam, Ganser, Arnold, Niederwieser, Dietger, Hallek, Michael, Savani, Bipin, Jindra, Pavel, Polge, Emmanuelle, Ehninger, Gerhard, Finke, Jürgen, Nagler, Arnon, Renate, Arnold, Rubio, Marie, Mohty, Mohamad, Schwerdtfeger, Rainer, Craddock, Charles, Kröger, Nicolaus

2016

Overview

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.

• Publisher: Springer Science and Business Media LLC,BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: [SDV.CAN]Life Sciences [q-bio]/Cancer / [SDV.IMM]Life Sciences [q-bio]/Immunology / [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology / [SDV]Life Sciences [q-bio] / Acute leukemia / Age / Aged / Allogeneic stem cell transplantation / Anti-leukemic effect / Cancer Research / Chemotherapy / ddc:no / Diseases of the blood and blood-forming organs / Female / Graft Survival / Graft versus host disease / Graft vs Host Disease / Graft vs Host Disease - etiology / Graft vs Host Disease - immunology / Hematology / Hematopoietic Stem Cell Transplantation / Hematopoietic Stem Cell Transplantation - adverse effects / Hematopoietic Stem Cell Transplantation - methods / Hematopoietic stem cells / Histocompatibility Testing / HLA matching / Humans / Leukemia / Leukemia, Myeloid, Acute / Leukemia, Myeloid, Acute - complications / Leukemia, Myeloid, Acute - mortality / Leukemia, Myeloid, Acute - therapy / Life Sciences / Lymphocytes / Male / Medicine / Medicine & Public Health / Middle Aged / Molecular Biology / Mortality / Neoplasms. Tumors. Oncology. Including cancer and carcinogens / Older patients / Older people / Oncology / Patients / RC254-282 / RC633-647.5 / Remission Induction / Retrospective Studies / Risk factors / Stem cell transplantation / Survival Analysis / Toxicity / Transplantation / Transplantation Conditioning / Transplantation Conditioning - methods / Unrelated donor / Unrelated Donors