Does FLT3 Mutation Impact Survival After Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia? A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis

• Type of Material: Article
• Authors: Abhinav Deol, Wayne State University; Salyka Sengsayadeth, Vanderbilt University; Kwang Woo Ahn, Medical College of Wisconsin; Hai-Lin Wang, Medical College of Wisconsin; Mahmoud Aljurf, King Faisal Specialist Hospital Center & Research; Joseph Harry Antin, Dana-Farber Cancer Institute; Minoo Battiwalla, National Heart Lung and Blood Institute; Martin Bornhauser, Universitatsklinikum Carl Gustav Carus; Jean-Yves Cahn, University Hospital, Grenoble; Bruce Camitta, Medical College of Wisconsin; Yi-Bin Chen, Massachusetts General Hospital; Corey S. Cutler, Dana-Farber Cancer Institute; Robert Peter Gale, Imperial College London; Siddhartha Ganguly, University of Kansas; Mehdi Hamadani, Medical College of Wisconsin; Yoshihiro Inamoto, National Cancer Center Hospital; Madan Jagasia, Vanderbilt University; Rammurti Kamble, Baylor College of Medicine; John Koreth, Dana-Farber Cancer Institute; Hillard M. Lazarus, University Hospitals Case Medical Center; Jane Liesveld, University of Rochester; Mark R. Litzow, Mayo Clinic; David I. Marks, University Hospitals Bristol NHS Trust; Taiga Nishihori, H. Lee Moffitt Cancer Center and Research Institute; Richard F. Olsson, Karolinska Institutet; Ran Reshef, Columbia University; Jacob M. Rowe, Shaare Zedek Medical Center; Ayman A. Saad, University of Alabama Birmingham; Mitchell Sabloff, University of Ottawa; Harry C. Schouten, Academische Ziekenhuis; Thomas C. Shea, University of North Carolina Health Care; Robert J. Soiffer, Dana-Farber Cancer Institute; Geoffrey L. Uy, Washington University School of Medicine; Edmund Waller, Emory University; Peter H. Wiernik, Our Lady of Mercy Medical Center; Baldeep Wirk, Seattle Cancer Care Alliance; Ann E. Woolfrey, Fred Hutchinson Cancer Research Center; Donald Bunjes, Universitatsklinkum Ulm; Steven Devine, Ohio State University; Marcos de Lima, University Hospitals Case Medical Center; Brenda M. Sandmaier, University of Washington; Dan Weisdorf, CIBMTR, NMDP/ Be The Match; Hanna Khoury, Emory University; Wael Saber, Medical College of Wisconsin
• Language: English
• Date: 2016-10-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 American Cancer Society.
• Final Published Version (URL): http://dx.doi.org/10.1002/cncr.30140
• Title of Journal or Parent Work: Cancer
• ISSN: 0008-543X
• Volume: 122
• Issue: 19
• Start Page: 3005
• End Page: 3014
• Grant/Funding Information: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement 5U24-CA076518 from the NCI, the NHLBI and the NIAID; a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with HRSA/DHHS; two Grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from Alexion; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Be the Match Foundation; *Bristol Myers Squibb Oncology; *Celgene Corporation; *Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Genentech, Inc.; Genzyme Corporation; *Gilead Sciences, Inc.; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; *Jazz Pharmaceuticals, Inc.; Jeff Gordon Children's Foundation; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc.; Mesoblast; *Millennium: The Takeda Oncology Co.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Neovii Biotech NA, Inc.; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Otsuka Pharmaceutical Co, Ltd. – Japan; Oxford Immunotec; Perkin Elmer, Inc.; Pharmacyclics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; *Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; *Sunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Telomere Diagnostics, Inc.; TerumoBCT; Therakos, Inc.; University of Minnesota; and *Wellpoint, Inc.
• Keywords: AML; DISTINCT; PROGNOSIS; GENE; FMS-like tyrosine kinase 3 (FLT3); Oncology; allogeneic stem cell transplantation; CYTOGENETICS; COMPLETE REMISSION; Science & Technology; 1 more; Life Sciences & Biomedicine; acute myeloid leukemia; 12 TRIALS; ALLOGENEIC TRANSPLANTATION; MINIMAL RESIDUAL DISEASE; TANDEM DUPLICATIONS
• Research Categories: Health Sciences, Oncology

Abstract

BACKGROUND: Patients with FMS like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (HCT). METHODS: Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were used to evaluate 511 adult patients with de novo AML who underwent HCT during 2008 through 2011 to determine whether FLT3 mutations had an impact on HCT outcomes. RESULTS: In total, 158 patients (31%) had FLT3 mutations. Univariate and multivariate analyses revealed an increased risk of relapse at 3 years in the FLT3 mutated group compared with the wild-type (WT) group (38% [95% confidence interval (CI), 30%-45%] vs 28% [95% CI, 24%-33%]; P=.04; relative risk, 1.60 [95% CI, 1.15-2.22] ; P=.0048). However, FLT3 mutation status was not significantly associated with nonrelapse mortality, leukemia-free survival, or overall survival. Although more patients in the FLT3 mutated group died from relapsed primary disease compared with those in the WT group (60% vs 46%), the 3-year overall survival rate was comparable for the 2 groups (mutated group: 49%; 95% CI, 40%-57%; WT group: 55%, 95% CI, 50%-60%; P=.20). CONCLUSIONS: The current data indicate that FLT3 mutation status did not adversely impact overall survival after HCT, and about 50% of patients with this mutation who underwent HCT were long-term survivors.