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, 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

Research output: Contribution to journalArticlepeer-review

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 23,400cells/μl vs. 3,600cells/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=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;59:662-667.

Original languageEnglish (US)
Pages (from-to)662-667
Number of pages6
JournalPediatric Blood and Cancer
Volume59
Issue number4
DOIs
StatePublished - Oct 2012

Keywords

  • Acute promyelocytic leukemia
  • APL
  • FLT3 mutation
  • Pediatric

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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