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FLT3 mutation status is a predictor of early death in pediatric acute promyelocytic leukemia: A report from the Children's Oncology Group
Author(s) -
Kutny Matthew A.,
Moser Barry K.,
Laumann Kristina,
Feusner James H.,
Gamis Alan,
Gregory John,
Larson Richard A.,
Powell Bayard L.,
Stock Wendy,
Willman Cheryl L.,
Woods William G.,
Meshinchi Soheil
Publication year - 2012
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24122
Subject(s) - medicine , acute promyelocytic leukemia , gastroenterology , cohort , acute leukemia , leukemia , biochemistry , retinoic acid , chemistry , gene
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 = 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. © 2012 Wiley Periodicals, Inc.