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. 2012 Oct;59(4):662-7.
doi: 10.1002/pbc.24122. Epub 2012 Feb 29.

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

Matthew A Kutny  1 , Barry K Moser, Kristina Laumann, James H Feusner, Alan Gamis, John Gregory, Richard A Larson, Bayard L Powell, Wendy Stock, Cheryl L Willman, William G Woods, Soheil Meshinchi
Affiliations

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

Matthew A Kutny et al. Pediatr Blood Cancer. 2012 Oct.

Abstract

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/µl vs. 3,600 cells/µl 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 = 8), 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.

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Figures

Figure 1
Figure 1
Induction Death in all patients (left) and in those with high WBC count (right) based on FLT3 mutation status.
Figure 2
Figure 2
Overall survival from study entry by FLT3 mutation status (A) and event free survival by FLT3 mutation status (B).
Figure 3
Figure 3
Relapse free survival from end of induction 1 by FLT3 mutation status.
See this image and copyright information in PMC

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