Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 2
© 2006 American Society of Clinical Oncology

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Paschka, P. Articles by Bloomfield, C. D. Search for Related Content PubMed Articles by Paschka, P. Articles by Bloomfield, C. D.

Abstract

Mutations of KIT tyrosine kinase (TK) gene predict relapse in adult patients (pts) with core binding factor acute myeloid leukemia (CBF AML): A Cancer and Leukemia Group B (CALGB) study

Ohio State University, Columbus, OH; University of Chicago, Chicago, IL; Cancer and Leukemia Group B, Chicago, IL

2

Background: Multi-course high-dose cytarabine (HDAC) has largely improved the outcome of CBF AML pts with t(8;21)(q22;q22) and inv(16)(p13q22). Yet, 50% of pts relapse within 5 years (yrs), indicating the need for markers identifying high-risk pts who require more aggressive and/or novel therapies. KIT mutations (mKIT) of exons 17 (mKIT17) and 8 (mKIT8) are good candidates to be such markers. Previous studies showed that mKIT17 impacted adversely on outcome of t(8;21), but not inv(16), pts. Methods: Sixty-one pts with inv(16) and 49 with t(8;21), assigned to HDAC consolidation on CALGB protocols,were analyzed at diagnosis for mKIT17 and mKIT8 by denaturing high-performance liquid chromatography and direct sequencing. The median follow-up was 5.3 yrs. Results: Among pts with inv(16), 10 had mKIT17 (3 with concurrent mKIT8) and 8 sole mKIT8; among pts with t(8;21), 9 had mKIT17 (2 with mKIT8) and 2 sole mKIT8. In each cytogenetic group, complete remission rates were similar for pts with wild-type KIT (wtKIT) and those with mKIT or mKIT17. In both groups, cumulative incidence of relapse (CIR) was higher for pts with any mKIT [inv(16), P=.050, 5-yr CIR 56% vs 29%; t(8;21), P=.017, 5-yr CIR 70% vs 36%], and also for the subsets of pts with mKIT17 [inv(16), P=.002, 5-yr CIR 80% vs 29%; t(8;21), P=.014, 5-yr CIR 75% vs 36%] compared to wtKIT. Neither mKIT nor mKIT17 significantly affected overall survival (OS). In multivariable analyses (see table), mKIT [in t(8;21)] and mKIT17 [in inv(16) and t(8;21)] independently predicted worse CIR; worse OS correlated significantly with mKIT only in inv(16) pts. Conclusions: We show for the first time that mKIT17 confer significantly higher relapse rates in inv(16) pts and confirm their adverse impact on t(8;21) pts. Thus, this subset of pts may benefit from more aggressive treatment and/or, since mKIT17 lead to constitutive KIT activation, from therapy that includes TK inhibitors, such as imatinib or PKC412.

No significant financial relationships to disclose.

Abstract presentation from the 2006 ASCO Annual Meeting