title: Novel tyrosine kinase inhibitor therapy before allogeneic stem cell transplantation in patients with chronic myeloid leukemia: no evidence for increased transplant-related toxicity.
abstract: BACKGROUND
  Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML) are increasingly likely to have received a novel tyrosine kinase inhibitor (NTKI) after failing imatinib mesylate. It is unknown whether the use of these NTKIs before HSCT increases transplant-related toxicity.
  
  
  METHODS
  The outcome of 12 patients with CML (1 in chronic phase, 6 in the accelerated phase, and 5 in the blastic phase) who received dasatinib (n = 2), nilotinib (n = 7), or both (n = 3) before HSCT were retrospectively analyzed.
  
  
  RESULTS
  The median time on treatment was 134 days, and the median time from the end of NTKI therapy to HSCT was 34 days. The preparative regimen was ablative in 8 patients and nonablative in 4. All patients engrafted within 13 days. There was no significant early transplant-related toxicity. One patient developed secondary graft failure after 6 months from the first HSCT that required a second HSCT. Acute and chronic graft-versus-host disease (GVHD) was observed in 7 and 6 patients, respectively. Nine patients achieved a molecular response: 4 complete and 5 major (quantitative reverse transcriptase-polymerase chain reaction <0.05%). Three patients had disease progression by Day 30 after HSCT. Two patients developed disease recurrence after a median of 12 months. After a median follow-up of 10 months, 7 patients were alive in molecular response and 5 patients had died, 4 of disease progression and 1 of extensive chronic GVHD.
  
  
  CONCLUSIONS
  Previous treatment with NTKI did not increase transplant-related toxicity in this preliminary experience. Further follow-up and a larger number of patients will be necessary to confirm these observations.
authors.affiliation: Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
authors.forename: Borje S
authors.initials: BS
authors.lastname: Andersson
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shpall
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D000069439:Dasatinib; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib