title: Allogeneic Hematopoietic Stem Cell Transplantation Is an Effective Salvage Therapy for Patients with Chronic Myeloid Leukemia Presenting with Advanced Disease or Failing Treatment with Tyrosine Kinase Inhibitors.
abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only known curative therapy for chronic myeloid leukemia (CML); however, it is rarely utilized given the excellent long-term results with tyrosine kinase inhibitor (TKI) treatment. The purpose of this study is to examine HSCT outcomes for patients with CML who failed TKI therapy or presented in advanced phase and to identify predictors of survival, relapse, and nonrelapse mortality (NRM). Fifty-one patients with CML underwent HSCT for advanced disease at diagnosis (n = 15), TKI resistance as defined by the European LeukemiaNet guidelines (n = 30), TKI intolerance (n = 2), or physician preference (n = 4). At a median follow-up of 71.9 months, the 8-year overall survival (OS), event-free survival (EFS), relapse, and NRM were 68%, 46%, 41%, and 23%, respectively. In univariate analysis, predictors of OS included first chronic phase (CP1) disease status at HSCT (P = .0005), European Society for Blood and Marrow Transplantation score 1 to 4 (P = .04), and complete molecular response (CMR) to HSCT (P < .0001). Donor (female) to patient (male) gender combination (P = .02) and CMR to HSCT (P < .0001) predicted lower relapse. In multivariate analysis, CMR to HSCT remained an independent predictor of OS (odds ratio [OR], 43), EFS (OR, 56) and relapse (OR, 29). This report indicates that the outlook is excellent for those patients who remain in CP1 at the time of HSCT and achieve a CMR after HSCT. However, only approximately 50% of those in advanced phase at HSCT are long-term survivors. This highlights the ongoing need to try to identify patients earlier, before disease progression, who are destined to fail this treatment to optimize transplantation outcomes.
authors: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada.
authors: Anish P
authors: AP
authors: Nair
authors: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada.
authors: Michael J
authors: MJ
authors: Barnett
authors: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada.
authors: Raewyn C
authors: RC
authors: Broady
authors: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada.
authors: Donna E
authors: DE
authors: Hogge
authors: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada.
authors: Kevin W
authors: KW
authors: Song
authors: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada.
authors: Cynthia L
authors: CL
authors: Toze
authors: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada.
authors: Stephen H
authors: SH
authors: Nantel
authors: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada.
authors: Maryse M
authors: MM
authors: Power
authors: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada.
authors: Heather J
authors: HJ
authors: Sutherland
authors: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada.
authors: Thomas J
authors: TJ
authors: Nevill
authors: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada.
authors: Yasser
authors: Y
authors: Abou Mourad
authors: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada.
authors: Sujaatha
authors: S
authors: Narayanan
authors: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada.
authors: Alina S
authors: AS
authors: Gerrie
authors: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: dforrest@bccancer.bc.ca.
authors: Donna L
authors: DL
authors: Forrest
mesh_terms: D000328:Adult; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016879:Salvage Therapy / Q000379:methods*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods*; D055815:Young Adult
chemical_list: D047428:Protein Kinase Inhibitors
keywords: Allogeneic stem cell transplantation; Chronic myeloid leukemia; Imatinib mesylate; Tyrosine kinase inhibitor