title: FLT3 mutational status is an independent risk factor for adverse outcomes after allogeneic transplantation in AML.
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.
authors.affiliation: University of Michigan Medical School, University of Michigan, Ann Arbor, MI, USA.|Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Yeohan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
authors.forename: John
authors.initials: J
authors.lastname: Magenau
authors.affiliation: School of Public Health, University of Michigan, Ann Arbor, MI, USA.|Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Yumeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Public Health, University of Michigan, Ann Arbor, MI, USA.|Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Dale
authors.initials: D
authors.lastname: Bixby
authors.affiliation: Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.|Bioinformatics Core, University of Michigan, Ann Arbor, MI, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hanauer
authors.affiliation: University of Michigan Medical School, University of Michigan, Ann Arbor, MI, USA.|Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Komal A
authors.initials: KA
authors.lastname: Chughtai
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Gatza
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Couriel
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Goldstein
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Attaphol
authors.initials: A
authors.lastname: Pawarode
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Pavan
authors.initials: P
authors.lastname: Reddy
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Riwes
authors.affiliation: Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.|Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: James
authors.initials: J
authors.lastname: Connelly
authors.affiliation: Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.|Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Harris
authors.affiliation: Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.|Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Kitko
authors.affiliation: Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.|Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: John
authors.initials: J
authors.lastname: Levine
authors.affiliation: Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.|Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Yanik
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Parkin
authors.affiliation: Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.|Hematological Malignancies and Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.|Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Choi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3