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Clinical Trial
. 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

Yeohan Song #  1   2 , John Magenau #  3   4   5 , Yumeng Li  6   7 , Thomas Braun  6   7 , Lawrence Chang  2 , Dale Bixby  3   4   5 , David A Hanauer  4   7   8 , Komal A Chughtai  1   2 , Erin Gatza  2 , Daniel Couriel  3   4   5 , Steven Goldstein  3   4   5 , Attaphol Pawarode  3   4   5 , Pavan Reddy  3   4   5 , Mary Riwes  3   4   5 , James Connelly  4   5   2 , Andrew Harris  4   5   2 , Carrie Kitko  4   5   2 , John Levine  4   5   2 , Greg Yanik  4   5   2 , Brian Parkin #  3   4   5 , Sung Won Choi #  4   5   2
Affiliations
Clinical Trial

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

Yeohan Song et al. Bone Marrow Transplant. 2016 Apr.

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.

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Figure 1
Figure 1
Three-year Cumulative Incidence Outcomes by FLT3 Mutational Status. A) Relapse Risk, B) Non-relapse Mortality, C) Disease-free Survival, D) Overall Survival Solid line: FLT3 mutation positive; Dashed line: FLT3 mutation negative
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References

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