title: Response to tyrosine kinase inhibitor therapy in patients with chronic myelogenous leukemia relapsing in chronic and advanced phase following allogeneic hematopoietic stem cell transplantation.
abstract: Tyrosine kinase inhibitors (TKI) have been used to treat relapse of chronic myelogenous leukemia (CML) after allogeneic stem cell transplant (HSCT), with responses seen predominantly in chronic phase (CP) patients. This study aimed to analyze the response to TKI therapy and overall survival for patients relapsing predominantly in advanced phase. We retrospectively reviewed 22 patients treated with imatinib (n=20) and/or dasatinib (n=6) for relapsed CML after HSCT; 8 patients were in CP, and 14 patients had advanced disease. Seven patients also received donor lymphocyte infusions. Hematologic, cytogenetic, and molecular responses were analyzed. Nineteen patients (86%) achieved complete hematologic response (CHR), 17 patients (77%) achieved complete cytogenetic response (CCR), and 14 patients (64%) achieved complete molecular response (CMR). In advanced phase patients, 11 (79%) achieved CHR, 10 (71%) CCR, and 8 (57%) achieved CMR. Grade 3 or 4 cytopenias occurred in 10 cases. With median follow-up of 31.5 months from relapse, 14 (64%) patients remain alive, 13 in CMR. In multivariate analysis, the achievement of CMR was significantly correlated with OS with an odds ratio of 20.5 (95% confidence interval 2.3-182) P=.007. TKI therapy is capable of inducing durable molecular responses for CML relapsing after HSCT, both in chronic and advanced phases. The achievement of CMR appears to be crucial in providing long-term disease control for these patients.
authors.affiliation: Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Wright
authors.forename: John D
authors.initials: JD
authors.lastname: Shepherd
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Barnett
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Nantel
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Sutherland
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Toze
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hogge
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Nevill
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Song
authors.forename: Yasser R
authors.initials: YR
authors.lastname: Abou Mourad
authors.forename: Sujaatha
authors.initials: S
authors.lastname: Narayanan
authors.forename: Maryse M
authors.initials: MM
authors.lastname: Power
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Smith
authors.forename: Donna L
authors.initials: DL
authors.lastname: Forrest
mesh_terms: D000328:Adult; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D015465:Leukemia, Myeloid, Accelerated Phase / Q000401:mortality / Q000628:therapy; D015466:Leukemia, Myeloid, Chronic-Phase / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases