Results of allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia patients who failed tyrosine kinase inhibitors after developing BCR-ABL1 kinase domain mutations

Elias Jabbour, Jorge Cortes, Fabio P.S. Santos, Dan Jones, Susan O'Brien, Gabriela Rondon, Uday Popat, Sergio Giralt, Partow Kebriaei, Roy B. Jones, Hagop Kantarjian, Richard Champlin, Marcos De Lima

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Hematopoietic stem cell transplantation (HSCT) is effective therapy for patients with chronic myelogenous leukemia (CML) but is now mostly indicated for patients who develop resistance to tyrosine kinase inhibitors (TKIs), which can be associated with point mutations in BCR-ABL1. We reviewed the outcomes of imatinib-resistant CML patients (chronic phase, n = 34; accelerated phase [AP], n = 9; and blast phase [BP], n = 4) who underwent HSCT and had BCR-ABL1 sequencing. Mutations were found in 19 patients (40%); 15 of 19 had advanced CML (AP + BP + second chronic phase). Patients with mutations were more likely to transform toAP/BPat time of imatinib failure (69% vs 35%, P = .03). Forty-two patients (89%) responded to HSCT: 32 (68%) had at least a major molecular response. The 2-year event-free survival was 36% and 58% (P = .05) for the mutant and nonmutant groups, respectively; and the 2-year overall survival was 44% and 76% (P = .02), respectively. HSCT is an important salvage option for TKI-resistant patients with or without BCR-ABL1 mutations. Patients with mutations were more likely to develop advanced disease and had worse outcomes after HSCT. HSCT should be considered early for patients deemed to have a low probability of responding to second-generation TKI.

Original languageEnglish (US)
Pages (from-to)3641-3647
Number of pages7
JournalBlood
Volume117
Issue number13
DOIs
StatePublished - Mar 31 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Jabbour, E., Cortes, J., Santos, F. P. S., Jones, D., O'Brien, S., Rondon, G., Popat, U., Giralt, S., Kebriaei, P., Jones, R. B., Kantarjian, H., Champlin, R., & De Lima, M. (2011). Results of allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia patients who failed tyrosine kinase inhibitors after developing BCR-ABL1 kinase domain mutations. Blood, 117(13), 3641-3647. https://doi.org/10.1182/blood-2010-08-302679