title: Outcome of patients with chronic myeloid leukemia with multiple ABL1 kinase domain mutations receiving tyrosine kinase inhibitor therapy.
abstract: We investigated the impact of carrying more than one BCR-ABL1 mutation in 207 patients with chronic myeloid leukemia (102 chronic, 61 accelerated, and 44 blast phase) post-imatinib failure. Seven (8%) of 92 patients carrying mutations had more than one mutation: 4 (4%) in chronic phase, 2 (2%) in accelerated phase, and one (1 %) in blast phase. The cytogenetic response rate to second generation TKIs for patients with no, one, or more than one mutation was 88%, 69%, 50% (P=0.03) in chronic phase, 54%, 42%, 50% in accelerated phase (P=0.67), and 35%, 25%, 0% (P=0.63) in blast phase, respectively. No differences were observed in event free survival or overall survival in accelerated or blast phase according to their mutational status. However, the 4-year event free survival rates among patients in chronic phase with no, one, or more than one BCR-ABL1 mutation were 56%, 49%, and 0%, respectively (P=0.02), with overall survival rates of 91%, 69%, and 75%, respectively (P=0.13). In conclusion, patients with more than one BCR-ABL1 mutation fare worse than those with no or one mutation.
authors.affiliation: UT Anderson Cancer Center, Department of Leukemia, Unit 428 1515 Holcombe Blvd. Houston, TX 77030, USA.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintás-Cardama
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Jianqin
authors.initials: J
authors.lastname: Shan
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases