Journal
BLOOD
Volume 115, Issue 12, Pages 2372-2379Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-09-241075
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Funding
- National Cancer Institute [5K12CA076930-08]
- St Baldrick's Foundation Career Development Award
- CureSearch Research Fellowship Award
- For Julie Foundation
- VA Merit Review Grant
- Leukemia & Lymphoma Society
- National Institutes of Health [R21 CA10262-01, R01 CA114563-01]
- Children's Oncology Group Chair [NIH U10 CA98543]
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KIT receptor tyrosine kinase mutations are implicated as a prognostic factor in adults with core binding factor (CBF) acute myeloid leukemia (AML). However, their prevalence and prognostic significance in pediatric CBF AML is not well established. We performed KIT mutational analysis (exon 8 and exon 17) on diagnostic specimens from 203 pediatric patients with CBF AML enrolled on 4 pediatric AML protocols. KIT mutations were detected in 38 (19%) of 203 (95% CI, 14%-25%) patient samples of which 20 (52.5%) of 38 (95% CI, 36%-69%) involved exon 8, 17 (45%) of 38 (95% CI, 29%-62%) involved exon 17, and 1 (2.5%; 95% CI, 0%-14%) involved both locations. Patients with KIT mutations had a 5-year event-free survival of 55% (+/- 17%) compared with 59% (+/- 9%) for patients with wild-type KIT (P = .86). Rates of complete remission, overall survival, disease-free survival, or relapse were not significantly different for patients with or without KIT mutations. Location of the KIT mutation and analysis by cytogenetic subtype [t(8; 21) vs inv(16)] also lacked prognostic significance. Our study shows that KIT mutations lack prognostic significance in a large series of pediatric patients with CBF AML. This finding, which differs from adult series and a previously published pediatric study, may reflect variations in therapeutic approaches and/or biologic heterogeneity within CBF AML. Two of 4 studies included in this analysis are registered at http://clinicaltrials.gov as NCT00002798(CCG-2961) and NCT00070174 (COG AAML03P1). (Blood. 2010; 115: 2372-2379)
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