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Impact of numerical variation in FMS-like tyrosine kinase receptor 3 internal tandem duplications on clinical outcome in normal karyotype acute myelogenous leukemia†
Article first published online: 17 MAY 2012
Copyright © 2012 American Cancer Society
Volume 118, Issue 23, pages 5819–5822, 1 December 2012
How to Cite
Borthakur, G., Kantarjian, H., Patel, K. P., Ravandi, F., Qiao, W., Faderl, S., Kadia, T., Luthra, R., Pierce, S. and Cortes, J. E. (2012), Impact of numerical variation in FMS-like tyrosine kinase receptor 3 internal tandem duplications on clinical outcome in normal karyotype acute myelogenous leukemia. Cancer, 118: 5819–5822. doi: 10.1002/cncr.27571
G.B. collected and analyzed the data, drafted the brief report, and provided clinical care to patients. H.K., F.R., S.F., T.K., and J.E.C. coauthored the article and provided clinical care to patients. S.P., K.P.P., R.L., and W.Q. collected data, analyzed results. and coauthored the article. W.Q. performed statistical analyses and coauthored the article.
- Issue published online: 19 NOV 2012
- Article first published online: 17 MAY 2012
- Manuscript Revised: 28 FEB 2012
- Manuscript Accepted: 28 FEB 2012
- Manuscript Received: 8 DEC 2011
- fms-like tyrosine kinase receptor;
- internal tandem duplications;
- normal karyotype acute myelogenous leukemia;
- relapse risk;
- internal tandem duplication mutation
The impact of single versus multiple fms-like tyrosine kinase receptor 3 internal tandem duplication (FLT3-ITD) mutations on the clinical outcome of patients with acute myelogenous leukemia has not been well studied, and particularly has not been investigated while simultaneously accounting for the quantitative mutation burden.
The authors conducted a multivariate analysis of overall survival, event-free survival, and complete remission duration, including numeric variation (single vs multiple) and quantitative mutant burden of FLT3-ITD as variables among other clinically relevant factors.
An analysis of a cohort of 1043 patients with AML demonstrated that, among patients with normal-karyotype acute myelogenous leukemia and FLT3-ITD mutation, overall survival and event-free survival were not affected by the number of FLT3-ITD mutations, but complete remission duration was significantly longer in patients who had multiple FLT3-ITD mutations (median, 86 weeks vs 34 weeks; P = .03).
The current results indicated that time-to-event analyses of patients with normal-karyotype acute myelogenous leukemia and FLT3-ITD mutation should take into account the number of mutations and the mutant burden, among other factors. Cancer 2012. © 2012 American Cancer Society.