title: Results of allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia patients who failed tyrosine kinase inhibitors after developing BCR-ABL1 kinase domain mutations.
abstract: Hematopoietic stem cell transplantation (HSCT) is effective therapy for patients with chronic myelogenous leukemia (CML) but is now mostly indicated for patients who develop resistance to tyrosine kinase inhibitors (TKIs), which can be associated with point mutations in BCR-ABL1. We reviewed the outcomes of imatinib-resistant CML patients (chronic phase, n = 34; accelerated phase [AP], n = 9; and blast phase [BP], n = 4) who underwent HSCT and had BCR-ABL1 sequencing. Mutations were found in 19 patients (40%); 15 of 19 had advanced CML (AP + BP + second chronic phase). Patients with mutations were more likely to transform to AP/BP at time of imatinib failure (69% vs 35%, P = .03). Forty-two patients (89%) responded to HSCT: 32 (68%) had at least a major molecular response. The 2-year event-free survival was 36% and 58% (P = .05) for the mutant and nonmutant groups, respectively; and the 2-year overall survival was 44% and 76% (P = .02), respectively. HSCT is an important salvage option for TKI-resistant patients with or without BCR-ABL1 mutations. Patients with mutations were more likely to develop advanced disease and had worse outcomes after HSCT. HSCT should be considered early for patients deemed to have a low probability of responding to second-generation TKI.
authors.affiliation: Department of Leukemia, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Fabio P S
authors.initials: FP
authors.lastname: Santos
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rondon
authors.forename: Uday
authors.initials: U
authors.lastname: Popat
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.forename: Roy B
authors.initials: RB
authors.lastname: Jones
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D020134:Catalytic Domain / Q000235:genetics; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017434:Protein Structure, Tertiary / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*; D014184:Transplantation, Homologous; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl