FLT3 mutation status is a predictor of early death in pediatric acute promyelocytic leukemia: A report from the Children's Oncology Group

Background FLT3 mutations (FLT3/Mut) are prevalent in de novo AML and are associated with early relapse. The prevalence and prognostic significance of FLT3/Mut have not been well defined in childhood acute promyelocytic leukemia (APL). Procedure Diagnostic specimens from 104 pediatric APL patients were screened for FLT3/Mut (FLT3/ITD or FLT3/ALM). FLT3/Mut status was correlated with disease characteristics and clinical outcome for patients treated on CALGB C9710 (n?=?50). Results Forty-two of the 104 patients (40%) had either FLT3/ITD (n?=?28, 27%) or FLT3/ALM (n?=?15, 14%). Median diagnostic WBC count was 23,400?cells/mu l vs. 3,600?cells/mu l for those with and without FLT3/Mut (P?<?0.001), and similar results for the cohort of 50 patients treated on C9710 (P?<?0.001). In patients treated on C9710, presence of a FLT3 mutation was highly correlated with diagnostic WBC count >10,000 (P?=?0.004), microgranular variant histology (P?=?0.035), and a lower remission rate (P?=?0.009). In patients who received ATRA (C9710 or CCG-2911, n?=?58), those with FLT3/Mut had an induction death rate of 30% (7/23) compared to 3% (1/35) in FLT3/WT patients (P?=?0.005). In patients with high WBC counts (>10,000), those with FLT3/Mut had a significantly higher risk of induction death versus FLT3/WT patients (47% vs. 0%, P?=?0.05). FLT3/Mut was not associated with adverse outcome in those who survived induction therapy. Conclusions FLT3/Mut are prevalent in pediatric APL and are associated with high WBC count and increased induction death. This study provides further evidence for testing APL patients for FLT3/Mut and the potential role for FLT3 inhibitors in this disease. Pediatr Blood Cancer 2012;59:662667. (c) 2012 Wiley Periodicals, Inc.