Allogeneic Stem Cell Transplantation in Patients With FLT3-ITD Mutated AML: Transplantation in CR1 Is the Decisive Factor for Good Outcome

Patients with internal tandem duplication in fms-related tyrosine kinase receptor gene 3 acute myeloid leukemia have a poor outcome and early allogeneic stem cell transplantation (alloSCT) seems to be the only curative modality. Our data confirm that early alloSCT remains the best consolidation therapy (even for older patients) and should be performed immediately in first complete remission (CR1). The unsatisfactory results with alloSCT beyond CR1 disqualify the policy of postponement stem cell transplantation until relapse and suggest that innovative approaches are needed for such patients. Background: Patients with internal tandem duplication in fms-related tyrosine kinase receptor gene 3 (FLT3-ITD)-mutated acute myeloid leukemia (AML) have a dismal prognosis and the only curative option seems to be allogeneic stem cell transplantation (alloSCT). However, its timing is still matter of debate. Patients and Methods: We retrospectively analyzed 73 consecutive AML patients with FLT3-ITD (median age 53, range 20-68 years) allografted with consistent policy to try to refer them all for upfront alloSCT in first complete remission (CR1). Results: With a median follow-up of 44 (range, 5-135) months the 5-year overall survival (OS)/disease-free survival (DFS) probabilities were 49%/47%. The cumulative incidence of relapse and nonrelapse mortality (NRM) were 37% and 14%, respectively. The estimated 5-year OS for patients who received transplantation in CR1 was 62% versus 0% for patients who received trans-plantation beyond CR1. Multivariable analysis identified stem cell transplantation beyond CR1 as the key factor for poor OS (hazard ratio [HR], 5.41; P < .0001), DFS (HR, 4.41; P = .0002), and high relapse incidence (HR, 8.08; P < .0001). Acute graft versus host disease Grade >= 3 predicted higher NRM (HR, 3.80; P = .059) as well as inferior OS (HR, 2.04; P = .0079). No association of patient age, nucleophosmin status, donor type, conditioning, and other variables on the survival was detected. Conclusion: AlloSCT should be regarded with urgency as soon as CR1 is achieved in this subset of AML patients.