Outcome of Childhood Acute Myeloid Leukemia With FLT3-ITD Mutation: The Experience of Children's Cancer Hospital Egypt, 2007-17

Abstract

Introduction: The presence of FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutation in pediatric acute myeloid leukemia (AML) is associated with high rates of induction failure and worse survival. Its presence places the patient into a high-risk group. We aimed to describe the outcome of pediatric AML with FLT3-ITD mutation.

Patients and methods: We performed a retrospective analysis of cases of AML from July 2007 till July 2017 at Children's Cancer Hospital Egypt.

Results: Seventy-one patients had FLT3 gene mutation out of 687 patients with AML. Sixty-five patients had FLT3 gene mutation with allelic ratio > 0.4; 43 (66.1%) of 65 patients experienced complete remission (CR). Of the 43 patients, 16 patients maintained CR, 18 patients relapsed after first CR, 8 patients died, and 1 patient was lost to follow-up. Patients with relapsing disease died after salvage chemotherapy, except for one patient, who was alive after second CR. Allogeneic bone marrow transplantation (allo-BMT) was performed for 9 (13.8%) of 65 patients in first CR, of whom 8 were alive and in CR, and 1 patient experienced disease relapse and died. Seven patients (10.7%) were alive without allo-BMT. Three years' overall and event-free survival for patients with FLT3-ITD mutation with high allelic ratio was 26.9% and 22.8%, respectively. Three years' overall and event-free survival for patients treated with allo-BMT was 77.8% and 78.8%, respectively, versus patients treated without allo-BMT, 16.3% and 12.8%, respectively.

Conclusion: FLT3-ITD mutation in pediatric AML was associated with poor treatment outcomes, and the survival of relapsing patients was extremely poor. Allo-BMT in first remission was the best treatment option. Alternative donor transplants and FLT3 inhibitors are needed to improve outcome in developing countries.

Keywords: AML induction failure; Bone marrow transplantation; FLT3 inhibitor; Minimal residual disease; Poor outcome of AML with FLT3-ITD mutation; Relapsing AML with FLT3-ITD mutation.