[1442] Prevalence and Prognostic Significance of c-KIT Mutations in Pediatric CBF AML Patients Enrolled on Serial CCG/COG Protocols. Session Type: Poster Session, Board #596-I

Jessica Pollard, Todd Alonzo, Robert Gerbing, Rong Zeng, Betsy Hirsch, Susana Raimondi, Nyla Heerema, William Woods, Beverly Lange, Craig Hurwitz, Robert Arceci, Jerald Radich, Irwin Bernstein, Michael Heinrich, Soheil Meshinchi Fred Hutchinson Cancer Research Center, Seattle, WA, USA; University of Washington, Seattle, WA, USA; University of Southern California Keck School of Medicine, Los Angeles, CA, USA; Childrens Oncology Group, Arcadia, CA, USA; University of Minnesota Cancer Center, Minneapolis, MN, USA; St Jude Childrens Research Hospital, Memphis, TN, USA; Ohio State University, Columbus, OH, USA; Childrens Healthcare of Atlanta/Emory University, Atlanta, GA, USA; Childrens Hospital of Philadelphia, Philadelphia, PA, USA; Maine Medical Center, Portland, ME, USA; Johns Hopkins Hospital, Baltimore, MD, USA; Oregon Health and Science University, Portland, OR, USA

Pediatric patients with core binding factor (CBF) acute myeloid leukemia (AML) [t(8;21) and inv(16)] typically have favorable outcome, yet 20-40% of patients will relapse, suggesting that additional events may impact disease response. Recently, mutations of the c-KIT receptor tyrosine kinase gene were implicated as a prognostic factor in adults with CBF AML. The prevalence and prognostic significance of c-KIT mutations in pediatric CBF AML has not been well established. We analyzed diagnostic specimens from 156 pediatric patients with CBF AML enrolled on serial AML protocols CCG 2891, 2961 and COG AAML03P1 with 3 different methodologies (direct sequencing, HPLC, and micro capillary electrophoresis) to identify mutations in c-KIT exons 8 and 17. Mutations were detected in 27 samples (17%); 13 (48%) involved exon 8, 13 (48%) involved exon 17, and 1 (4%) involved both regions. Of 15 inv(16) specimens with c-KIT mutations, 9 (60%) involved exon 8, 5 (33%) involved exon 17, and 1 (7%) affected both exons. In contrast, of 12 t(8;21) specimens with c-KIT mutations, 4 (33%) involved exon 8 whereas 8 (67%) affected exon 17. Clinical outcome data from 98 CBF AML patients enrolled on CCG 2961 was analyzed to determine the prognostic significance of c-KIT mutations in this patient population. CBF AML patients with c-KIT mutations had similar clinical characteristics (age, sex, race, presenting white blood cell count and blast percentage) to those CBF AML patients without c-KIT mutations. There was no difference in the rate of complete remission (CR) (c-KIT mutations, 88% vs. no mutation 92%; p=0.645), overall survival (OS) at 5 years from study entry (c-KIT mutation, 68% vs. no mutation 71%; p=0.733), or corresponding relapse risk (RR) from the time of CR (c-KIT mutations, 33% vs. no mutation 31%; p=0.92). The relative prognostic significance of the location of c-KIT mutation (i.e. exon 8 or exon 17) was also evaluated. No differences were found in CR rates (exon 8 mutation, 100% vs. exon 17 mutation, 75%; p= 0.467), OS from CR (exon 8 mutation, 86% vs. exon 17 mutation, 47%; p=0.088), or corresponding RR at 5 years from CR (exon 8 mutation, 29% vs. exon 17 mutation, 50%; p=0.517). This study demonstrates that the prevalence of c-KIT mutations in pediatric CBF AML patients enrolled on serial CCG/COG AML protocols is lower than that observed in adult studies. We found that c-KIT mutations lacked prognostic significance in pediatric CBF AML patients treated with intensive chemotherapy on CCG 2961, though there was a suggestion that patients with exon 17 mutations may have worse outcome. Outcome data from the entire cohort (CCG 2891, 2961 and COG AAML03P1) will be analyzed to determine whether this finding is significant with larger scale analysis.
Abstract #1442 appears in Blood, Volume 110, issue 11, November 16, 2007
Keywords: Acute Myeloid Leukemia|Kit|Pediatric
Disclosure: No relevant conflicts of interest to declare.

Saturday, December 8, 2007 5:30 PM

Session Info:  Poster Session: Molecular and Cytogenetic Markers and MRD in Pediatric AML and ALL (5:30 p.m.-7:30 p.m.)