Novel tyrosine kinase inhibitor therapy before allogeneic stem cell transplantation in patients with chronic myeloid leukemia: no evidence for increased transplant-related toxicity

Cancer. 2007 Jul 15;110(2):340-4. doi: 10.1002/cncr.22778.

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.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / therapeutic use*
  • Combined Modality Therapy
  • Dasatinib
  • Female
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / surgery
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrimidines / therapeutic use*
  • Thiazoles / therapeutic use*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Thiazoles
  • Protein-Tyrosine Kinases
  • nilotinib
  • Dasatinib