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Acute Leukemia

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

Bone Marrow Transplantation volume 51, pages 511–520 (2016)Cite this article

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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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Acknowledgements

We are grateful to the patients, their families and the clinical personnel who participated in this study. We thank Tracey Churay and Ashley Crouch and the BMT Program Team at the University of Michigan Clinical Trials Office for data collection and management. SWC is an A Alfred Taubman Institute/Edith Briskin/SKS Foundation Emerging Scholar. SWC is supported by a grant from the National Institutes of Health (1K23AI091623).

Author contributions

YS collected and analyzed data and drafted and approved the manuscript; YL analyzed data and approved the manuscript; LC, DAH, KAC and EG collected data and approved the manuscript; DC, SG, AP, PR, MR, JC, AH, CK, JL and GY cared for patients and approved the manuscript; TB designed the study, analyzed data and approved the manuscript; JM, BP and DB designed the study, cared for patients and approved the manuscript. SWC designed the study, cared for patients, collected and analyzed data and drafted and approved the manuscript.

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Author notes

  1. Y Song, J Magenau, B Parkin and S W Choi: These authors contributed equally to this work.

Authors and Affiliations

  1. University of Michigan Medical School, University of Michigan, Ann Arbor, MI, USA

    Y Song & K A Chughtai

  2. Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA

    Y Song, L Chang, D A Hanauer, K A Chughtai, E Gatza, J Connelly, A Harris, C Kitko, J Levine, G Yanik & S W Choi

  3. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

    J Magenau, D Bixby, D Couriel, S Goldstein, A Pawarode, P Reddy, M Riwes & B Parkin

  4. Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA

    J Magenau, D Bixby, D A Hanauer, D Couriel, S Goldstein, A Pawarode, P Reddy, M Riwes, J Connelly, A Harris, C Kitko, J Levine, G Yanik, B Parkin & S W Choi

  5. Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA

    J Magenau, D Bixby, D Couriel, S Goldstein, A Pawarode, P Reddy, M Riwes, J Connelly, A Harris, C Kitko, J Levine, G Yanik, B Parkin & S W Choi

  6. School of Public Health, University of Michigan, Ann Arbor, MI, USA

    Y Li & T Braun

  7. Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA

    Y Li & T Braun

  8. Bioinformatics Core, University of Michigan, Ann Arbor, MI, USA

    D A Hanauer

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  1. Y Song
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  2. J Magenau
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Correspondence to S W Choi.

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Song, Y., Magenau, J., Li, Y. et al. FLT3 mutational status is an independent risk factor for adverse outcomes after allogeneic transplantation in AML. Bone Marrow Transplant 51, 511–520 (2016). https://doi.org/10.1038/bmt.2015.170

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