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

Abhinav Deol, Salyka Sengsayadeth, Kwang Woo Ahn, Hai Lin Wang, Mahmoud Aljurf, Joseph Harry Antin, Minoo Battiwalla, Martin Bornhauser, Jean Yves Cahn, Bruce Camitta, Yi Bin Chen, Corey S. Cutler, Robert Peter Gale, Siddhartha Ganguly, Mehdi Hamadani, Yoshihiro Inamoto, Madan Jagasia, Rammurti Kamble, John Koreth, Hillard M. LazarusJane Liesveld, Mark R. Litzow, David I. Marks, Taiga Nishihori, Richard F. Olsson, Ran Reshef, Jacob M. Rowe, Ayman A. Saad, Mitchell Sabloff, Harry C. Schouten, Thomas C. Shea, Robert J. Soiffer, Geoffrey L. Uy, Edmond K. Waller, Peter H. Wiernik, Baldeep Wirk, Ann E. Woolfrey, Donald Bunjes, Steven Devine, Marcos de Lima, Brenda M. Sandmaier, Dan Weisdorf, Hanna Jean Khoury, Wael Saber

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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%]; P5.04; relative risk, 1.60 [95% CI, 1.15-2.22]; P5.0048). 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%; P5.20). 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.

Original languageEnglish (US)
Pages (from-to)3005-3014
Number of pages10
JournalCancer
Volume122
Issue number19
DOIs
StatePublished - Oct 2016

Bibliographical note

Funding Information:
The Center for International Blood and Marrow Transplant Research (CIBMTR) is supported by a Public Health Service grant (cooperative agreement 5U24-CA076518) from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); by the NHLIB and the NCI (grant/cooperative agreement 5U10HL069294); by the Health Resources and Services Administration/Department of Health and Human Services (contract HHSH250201200016C; grants N00014-13-1-0039 and N00014-14-1-0028) from the Office of Naval Research; by an anonymous donation to the Medical College of Wisconsin; and by grants from Alexion; Amgen, Inc (a corporate member); Be the Match Foundation; Bristol-Myers Squibb Oncology (a corporate member); Celgene Corporation (a corporate member); Chimerix, Inc (a corporate member); the Fred Hutchinson Cancer Research Center; Gamida Cell Ltd; Genentech, Inc; Genzyme Corporation; Gilead Sciences, Inc (a corporate member); Health Research, Inc; the Roswell Park Cancer Institute; HistoGenetics, Inc; Incyte Corporation; Jazz Pharmaceuticals, Inc (a corporate member); Jeff Gordon Children?s Foundation; The Leukemia and Lymphoma Society; The Medical College of Wisconsin; Merck and Company, Inc; Mesoblast; Millennium: The Takeda Oncology Company; Miltenyi Biotec, Inc (a corporate member); the National Marrow Donor Program; Neovii Biotech NA, Inc; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Health Care Solutions, Inc; Otsuka America Pharmaceutical, Inc; Otsuka Pharmaceutical Company, Ltd-Japan; Oxford Immunotec; Perkin Elmer, Inc; Pharmacyclics; Sanofi US (a corporate member); Seattle Genetics; Sigma-Tau Pharmaceuticals; Spectrum Pharmaceuticals, Inc (a corporate member); St Baldrick?s Foundation; Sunesis Pharmaceuticals, Inc (a corporate member); Swedish Orphan Biovitrum, Inc; Telomere Diagnostics, Inc; TerumoBCT; Therakos, Inc; the University of Minnesota; and Wellpoint, Inc (a corporate member).

Funding Information:
The Center for International Blood and Marrow Transplant Research (CIBMTR) is supported by a Public Health Service grant (cooperative agreement 5U24-CA076518) from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); by the NHLIB and the NCI (grant/cooperative agreement 5U10HL069294); by the Health Resources and Services Administration/Department of Health and Human Services (contract HHSH250201200016C; grants N00014-13-1-0039 and N00014-14-1-0028) from the Office of Naval Research; by an anonymous donation to the Medical College of Wisconsin; and by grants from Alexion; Amgen, Inc (a corporate member); Be the Match Foundation; Bristol-Myers Squibb Oncology (a corporate member); Celgene Corporation (a corporate member); Chimerix, Inc (a corporate member); the Fred Hutchinson Cancer Research Center; Gamida Cell Ltd; Genentech, Inc; Genzyme Corporation; Gilead Sciences, Inc (a corporate member); Health Research, Inc; the Roswell Park Cancer Institute; HistoGenetics, Inc; Incyte Corporation; Jazz Pharmaceuticals, Inc (a corporate member); Jeff Gordon Children’s Foundation; The Leukemia and Lymphoma Society; The Medical College of Wisconsin; Merck and Company, Inc; Mesoblast; Millennium: The Takeda Oncology Company; Miltenyi Biotec, Inc (a corporate member); the National Marrow Donor Program; Neovii Biotech NA, Inc; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Health Care Solutions, Inc; Otsuka America Pharmaceutical, Inc; Otsuka Pharmaceutical Company, Ltd-Japan; Oxford Immunotec; Perkin Elmer, Inc; Pharmacyclics; Sanofi US (a corporate member); Seattle Genetics; Sigma-Tau Pharmaceuticals; Spectrum Pharmaceuticals, Inc (a corporate member); St Baldrick’s Foundation; Sunesis Pharmaceuticals, Inc (a corporate member); Swedish Orphan Biovi-trum, Inc; Telomere Diagnostics, Inc; TerumoBCT; Therakos, Inc; the University of Minnesota; and Wellpoint, Inc (a corporate member).

Publisher Copyright:
© 2016 American Cancer Society.

Keywords

  • 1 more
  • Acute myeloid leukemia
  • Allogeneic stem cell transplantation
  • FMS-like tyrosine kinase 3 (FLT3)

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