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Prognostic significance of alterations in IDH enzyme isoforms in patients with AML treated with high‐dose cytarabine and idarubicin
Author(s) -
Ravandi Farhad,
Patel Keyur,
Luthra Rajyalakshmi,
Faderl Stefan,
Konopleva Marina,
Kadia Tapan,
Brandt Mark,
Pierce Sherry,
Kornblau Steven,
Andreeff Michael,
Wang Xuemei,
GarciaManero Guillermo,
Cortes Jorge,
Kantarjian Hagop
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26580
Subject(s) - idarubicin , idh2 , idh1 , medicine , cytarabine , myeloid leukemia , oncology , npm1 , karyotype , cancer research , gastroenterology , biology , genetics , mutation , gene , chromosome
Abstract BACKGROUND: IDH1 and IDH2 gene mutations are novel, recurring molecular aberrations among patients with normal karyotype acute myeloid leukemia (AML). METHODS: Among 358 patients with AML treated on 4 protocols using high‐dose ara‐C plus idarubicin induction, pretreatment samples were available for 170 (median age 53 years, [range, 17‐73]; 96% ≤65) and were evaluated for IDH1R132 , IDH2R172 , and IDH2R140 mutations or the codon 105 single nucleotide polymorphism (SNP) in IDH 1. RESULTS: IDH1 and IDH2 mutations were present in 12 (7%) and 24 (14%) of patients, and IDH1 G105 SNP in 24 (14%). Overall, 52 (30%) patients had IDH gene alterations. There was no association with complete response (CR), remission duration, overall survival, and event‐free survival and any of the IDH alterations, and no association with a higher CR rate or survival with the 4 regimens for the 52 patients with aberrant IDH . Among the patients with diploid karyotype and NPM1 mut FLT3 WT genotype, those with IDH1 or IDH2 mutations had an inferior outcome. CONCLUSIONS: IDH aberrations and IDH1 codon 105 SNP occur in about 30% of younger patients with AML, mostly with diploid karyotype. Using high‐dose ara‐C‐based induction regimens, we did not detect an association with outcome for any of the aberrations. Cancer 2011;. © 2011 American Cancer Society.