Epidemiologic study on survival of chronic myeloid leukemia and Ph + acute lymphoblastic leukemia patients with BCR-ABL T315I mutation

Franck E. Nicolini, Michael J. Mauro, Giovanni Martinelli, Dong Wook Kim, Simona Soverini, Martin C. Müller, Andreas Hochhaus, Jorge Cortes, Charles Chuah, Inge H. Dufva, Jane F. Apperley, Fumiharu Yagasaki, Jay D. Pearson, Senaka Peter, Cesar Sanz Rodriguez, Claude Preudhomme, Francis Giles, John M. Goldman, Wei Zhou

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Abstract

The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP), or blastic-phase (BP) and Philadelphia chromosome-positive (Ph)+ acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation detection was 54 years; 57% cases were men. Median time between TKI treatment initiation and T315I mutation detection was 29.2, 15.4, 5.8, and 9.1 months, respectively, for CP, AP, BP, and Ph+ ALL patients. After T315I mutation detection, second-generation TKIs were used in 56% of cases, hydroxyurea in 39%, imatinib in 35%, cytarabine in 26%, MK-0457 in 11%, stem cell transplantation in 17%, and interferon-α in 6% of cases. Median overall survival from T315I mutation detection was 22.4, 28.4, 4.0, and 4.9 months, and median progression-free survival was 11.5, 22.2, 1.8, and 2.5 months, respectively, for CP,AP, BP, and Ph+ ALL patients. These results confirm that survival of patients harboring a T315I mutation is dependent on disease phase at the time of mutation detection.

Original languageEnglish (US)
Pages (from-to)5271-5278
Number of pages8
JournalBlood
Volume114
Issue number26
DOIs
StatePublished - Dec 17 2009

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Nicolini, F. E., Mauro, M. J., Martinelli, G., Kim, D. W., Soverini, S., Müller, M. C., Hochhaus, A., Cortes, J., Chuah, C., Dufva, I. H., Apperley, J. F., Yagasaki, F., Pearson, J. D., Peter, S., Rodriguez, C. S., Preudhomme, C., Giles, F., Goldman, J. M., & Zhou, W. (2009). Epidemiologic study on survival of chronic myeloid leukemia and Ph + acute lymphoblastic leukemia patients with BCR-ABL T315I mutation. Blood, 114(26), 5271-5278. https://doi.org/10.1182/blood-2009-04-219410