Unrelated Donor Allogeneic Transplantation after Failure of Autologous Transplantation for Acute Myelogenous Leukemia: A Study from the Center for International Blood and Marrow Transplantation Research

• Type of Material: Article
• Authors: James M. Foran, Mayo Clinic; Steven Z. Pavletic, National Cancer Institute; Brent R. Logan, Medical College of Wisconsin; Manza A. Agovi-Johnson, University of South Carolina; Waleska S. Perez, Medical College of Wisconsin; Brian J. Bolwell, Cleveland Clinic Foundation; Martin Bornhaeuser, Universitatsklinikum Carl Gustav Carus; Christopher N. Bredeson, Ottawa Hospital; Mitchell S. Cairo, New York Medical College; Bruce M. Camitta, Children's Hospital of Wisconsin; Edward A. Copelan, Cleveland Clinic Foundation; Jason Dehn, National Marrow Donor Program; Robert P. Gale, Imperial College; Biju George, Christian Medical College Hospital; Vikas Gupta, Princess Margaret Hospital; Gregory A. Hale, University of South Florida; Hillard M. Lazarus, University Hospitals of Cleveland; Mark R. Litzow, Mayo Clinic; Dipnarine Maharaj, Bethesda Health City; Edmund K Waller, Emory University
• Language: English
• Date: 2013-07-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 American Society for Blood and Marrow Transplantation.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbmt.2013.04.022
• Title of Journal or Parent Work: Biology of Blood and Marrow Transplantation
• ISSN: 1083-8791
• Volume: 19
• Issue: 7
• Start Page: 1102
• End Page: 1108
• Grant/Funding Information: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children’s Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, Inc.; and Wellpoint, Inc.
• Keywords: Acute myelogenous leukemia; ADULT PATIENTS; STEM-CELL TRANSPLANTATION; THERAPY; Unrelated donor; ACUTE MYELOID-LEUKEMIA; 1ST REMISSION; Immunology; CHEMOTHERAPY; SURVIVAL; RELAPSE; Life Sciences & Biomedicine; Allogeneic; HEMATOLOGIC MALIGNANCIES; CONDITIONING REGIMEN; Transplantation; Hematology; Science & Technology; Autologous
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Immunology; Health Sciences, Oncology

Abstract

The survival of patients with relapsed acute myelogenous leukemia (AML) after autologous hematopoietic stem cell transplantation (auto-HCT) is very poor. We studied the outcomes of 302 patients who underwent secondary allogeneic hematopoietic cell transplantation (allo-HCT) from an unrelated donor (URD) using either myeloablative (n= 242) or reduced-intensity conditioning (RIC; n= 60) regimens reported to the Center for International Blood and Marrow Transplantation Research. After a median follow-up of 58 months (range, 2 to 160 months), the probability of treatment-related mortality was 44% (95% confidence interval [CI], 38%-50%) at 1-year. The 5-year incidence of relapse was 32% (95% CI, 27%-38%), and that of overall survival was 22% (95% CI, 18%-27%). Multivariate analysis revealed a significantly better overal survival with RIC regimens (hazard ratio [HR], 0.51; 95% CI, 0.35-0.75; P <.001), with Karnofsky Performance Status score ≥90% (HR, 0.62; 95% CI, 0.47-0.82: P= .001) and in cytomegalovirus-negative recipients (HR, 0.64; 95% CI, 0.44-0.94; P= .022). A longer interval (>18 months) from auto-HCT to URD allo-HCT was associated with significantly lower riak of relapse (HR, 0.19; 95% CI, 0.09-0.38; P <.001) and improved leukemia-free survival (HR, 0.53; 95% CI, 0.34-0.84; P= .006). URD allo-HCT after auto-HCT relapse resulted in 20% long-term leukemia-free survival, with the best results seen in patients with a longer interval to secondary URD transplantation, with a Karnofsky Performance Status score ≥90%, in complete remission, and using an RIC regimen. Further efforts to reduce treatment-related mortaility and relapse are still needed.