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Bone Marrow Transplant. 2016 Apr;51(4):511-520. doi: 10.1038/bmt.2015.170. Epub 2015 Jul 20.

FLT3 mutational status is an independent risk factor for adverse outcomes after allogeneic transplantation in AML.

Song Y#1,2, Magenau J#3,4,5, Li Y6,7, Braun T6,7, Chang L2, Bixby D3,4,5, Hanauer DA4,7,8, Chughtai KA1,2, Gatza E2, Couriel D3,4,5, Goldstein S3,4,5, Pawarode A3,4,5, Reddy P3,4,5, Riwes M3,4,5, Connelly J4,5,2, Harris A4,5,2, Kitko C4,5,2, Levine J4,5,2, Yanik G4,5,2, Parkin B#3,4,5, Choi SW#4,5,2.

Author information

1
University of Michigan Medical School, University of Michigan, Ann Arbor, MI, USA.
2
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
3
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
4
Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
5
Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
6
School of Public Health, University of Michigan, Ann Arbor, MI, USA.
7
Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
8
Bioinformatics Core, University of Michigan, Ann Arbor, MI, USA.
#
Contributed equally

Abstract

Allogeneic hematopoietic cell transplantation (HCT) has been increasingly used in the setting of FMS-like tyrosine kinase-3 (FLT3)-mutated AML. However, its role in conferring durable relapse-free intervals remains in question. Herein we sought to investigate FLT3 mutational status on transplant outcomes. We conducted a retrospective cohort study of 262 consecutive AML patients who underwent first-time allogeneic HCT (2008-2014), of whom 171 had undergone FLT3-ITD (internal tandem duplication) mutational testing. FLT3-mutated AML was associated with nearly twice the relapse risk (RR) compared with those without FLT3 mutation 3 years post-HCT (63% vs 37%, P<0.001) and with a shorter median time to relapse (100 vs 121 days). FLT3 mutational status remained significantly associated with this outcome after controlling for patient, disease and transplant-related risk factors (P<0.05). Multivariate analysis showed a significant association of FLT3 mutation with increased 3-year RR (hazard ratio (HR) 3.63, 95% confidence interval (CI): 2.13, 6.19, P<0.001) and inferior disease-free survival (HR 2.05, 95% CI: 1.29, 3.27, P<0.01) and overall survival (HR 1.92, 95% CI: 1.14, 3.24, P<0.05). These data demonstrate high risk of early relapse after allogeneic HCT for FLT3-mutated AML that translates into adverse disease-free and overall survival outcomes. Additional targeted and coordinated interventions are needed to maintain durable remission after allogeneic HCT in this high-risk population.

PMID:
26191952
PMCID:
PMC4720584
DOI:
10.1038/bmt.2015.170
[Indexed for MEDLINE]
Free PMC Article

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