Prognostic Factors, FLT-3 Mutations, and Treatment Outcomes with Pediatric-Inspired Protocols in Adolescent and Young Adults and Adult Patients with Acute Lymphoblastic Leukemia.

Abstract

Introduction: The treatment protocols of adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) have evolved, with the advent of pediatric-based regimens, measurable residual disease monitoring, and mutation analysis. Among the latter, previous reports have identified FLT-3 mutations in up to 5% of pediatric patients; however, the full clinical significance of these mutations in the non-pediatric population is still uncertain.

Methods: Our cohort includes AYA patients with ALL treated with the NY-II and BFM protocols at different time periods, allowing analysis of prognostic factors and survival outcomes. Additionally, we analyzed DNA samples for FLT-3 mutations, focusing on the potential prognostic implications and treatment responses within our cohort.

Results: No significant differences were found in overall survival or progression-free survival between the two treatment protocols. However, a higher rate of hematopoietic stem-cell transplantation was noted in the NY-II patients. Older age and high WBC count at presentation were identified as adverse prognostic factors using multivariate analysis. FLT-3 mutations were identified in 4 patients (5%) of the cohort, with only 1 patient having FLT-3 internal tandem duplication mutation and 3 patients having FLT-3-tyrosine kinase domain mutations.

Conclusions: The low rate and variability of FLT-3 mutations in an Israeli cohort precludes broad conclusions regarding their prognostic significance. In our cohort, age and WBC count but not treatment protocol or FLT-3 mutations influenced survival.