Stem cell transplantation for patients with chronic myeloid leukemia resistant to tyrosine kinase inhibitors with BCR-ABL kinase domain mutation T315I

Nikolai Velev, Jorge Cortes, Richard Champlin, Dan Jones, Gabriela Rondon, Sergio Giralt, Gautam Borthakur, Hagop M. Kantarjian, Marcos De Lima

Research output: Contribution to journalArticle

25 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3631-3637
Number of pages7
JournalCancer
Volume116
Issue number15
DOIs
StatePublished - Aug 1 2010
Externally publishedYes

    Fingerprint

Keywords

  • Chronic myeloid leukemia
  • Resistance
  • Stem cell transplantation
  • T315I

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Velev, N., Cortes, J., Champlin, R., Jones, D., Rondon, G., Giralt, S., Borthakur, G., Kantarjian, H. M., & De Lima, M. (2010). Stem cell transplantation for patients with chronic myeloid leukemia resistant to tyrosine kinase inhibitors with BCR-ABL kinase domain mutation T315I. Cancer, 116(15), 3631-3637. https://doi.org/10.1002/cncr.25092