title: Second-generation tyrosine kinase inhibitors combined with stem cell transplantation in patients with imatinib-refractory chronic myeloid leukemia.
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.
authors.affiliation: Department of Hematology and Bone Marrow Transplantation Center, The First Affiliated Hospital of Zhejiang University, Hangzhou, China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Jimin
authors.initials: J
authors.lastname: Shi
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cai
authors.forename: He
authors.initials: H
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D001549:Benzamides / Q000008:administration & dosage*; D002648:Child; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D033581:Stem Cell Transplantation / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate