title: Stem cell transplantation for patients with chronic myeloid leukemia resistant to tyrosine kinase inhibitors with BCR-ABL kinase domain mutation T315I.
abstract: BACKGROUND
  Resistance to tyrosine kinase inhibitor (TKIs) therapy is associated with the development of kinase domain mutations. Although many imatinib-resistant mutations respond well to second-generation TKIs, the threonine-to-isoleucine mutation at codon 315 of the breakpoint cluster region/v-abl Abelson murine leukemia viral oncogene protein fusion Bcr-Abl (T315I) is insensitive to all currently available TKIs. The outcome in such patients after stem cell transplantation (SCT) is unknown.
  
  
  METHODS
  Eight patients with TKI-resistant CML who had T315I mutations underwent 9 transplantations. At the time of SCT, 2 patients were in chronic phase, 3 patients were in accelerated phase; and 3 patients were in second chronic phase.
  
  
  RESULTS
  The best responses after SCT were a complete molecular response (CMR) in 3 patients, a complete cytogenetic response (CCyR) in 4 patients, and a complete hematologic response (CHR) in 1 patient, and 1 patient had no response. The best outcome was for patients who underwent transplantation in chronic phase, and both of those patients remained alive and in complete molecular remission 14 months and 42 months after SCT. After a median follow-up of 13 months from SCT, 5 patients remained alive, including 3 patients in CMR, 1 patient in CCyR, and 1 patient in CHR.
  
  
  CONCLUSIONS
  The current results indicated that SCT is an effective strategy for patients with CML who have the T315I mutation, particularly in earlier stages.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Velev
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rondon
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Marcos
authors.initials: M
authors.lastname: De Lima
mesh_terms: D000328:Adult; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000628:therapy*; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl