Second-generation tyrosine kinase inhibitors combined with stem cell transplantation in patients with imatinib-refractory chronic myeloid leukemia

Am J Med Sci. 2014 Jun;347(6):439-45. doi: 10.1097/MAJ.0000000000000186.

Abstract

Background: Allogeneic stem cell transplantation (allo-SCT) remains a curative therapy for chronic myeloid leukemia with advanced diseases, but limited data exist on the efficacy of short-time 2nd-generation tyrosine kinase inhibitors (TKIs) used before and after allo-SCT for patients failing imatinib therapy.

Methods: We present a single-center report of a series of 12 imatinib-refractory patients in advanced phases, 9 of whom harbored BCR-ABL1 mutations. All of them were treated with 2nd TKI, followed by allo-SCT.

Results: Dasatinib or nilotinib reinduced complete hematologic responses in 11 patients and complete cytogenetic responses in 4 patients. All patients engrafted successfully. Five patients experienced acute graft-versus-host-disease (GVHD), including 4 with grade III-IV disease. Four patients experienced chronic GVHD, including 1 with extensive disease. Post-transplant prophylactic dasatinib or nilotinb was administrated in 9 patients and discontinued 1 year later, all of whom sustained complete molecular remission, even after a median follow-up of 13 months after withdrawal of the TKI. No hematologic relapse was observed. Four patients died: 1 of primary disease and 3 of transplant-related complications. After a median follow-up of 28 months (range, 12-37 months) after SCT, 8 (66.7%) of 12 patients are alive, including 7 with complete molecular remission.

Conclusions: Allo-SCT has a satisfactory outcome when combined with 2nd-generation TKI, which could provide a good quality of remission before transplantation and prevent relapse after transplantation.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Benzamides / administration & dosage*
  • Child
  • Combined Modality Therapy / methods
  • Female
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Male
  • Middle Aged
  • Piperazines / administration & dosage*
  • Prospective Studies
  • Protein Kinase Inhibitors / administration & dosage*
  • Pyrimidines / administration & dosage*
  • Stem Cell Transplantation / methods*
  • Transplantation, Homologous
  • Young Adult

Substances

  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate