Prognostic factors and survival outcomes in patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era: Cohort study of 477 patients

Cancer. 2017 Nov 15;123(22):4391-4402. doi: 10.1002/cncr.30864. Epub 2017 Jul 25.

Abstract

Background: Outcomes in patients with chronic myeloid leukemia in blast phase (CML-BP) are historically dismal. Herein, the authors sought to analyze the characteristics, prognostic factors, and survival outcomes in patients with CML-BP in the tyrosine kinase inhibitor (TKI) era.

Methods: A total of 477 patients with CML-BP were treated with a TKI at some point during the course of their CML. Cox proportional hazard models identified characteristics that were predictive of survival. Overall survival and failure-free survival were assessed. Optimal cutoff points for specific parameters were identified using classification and regression tree (CART) analysis.

Results: The median age of the patients was 53 years (range, 16-84 years) and 64% were male. Approximately 80% of patients initially were diagnosed in the chronic phase of CML at a median of 41 months (range, 0.7-298 months) before transformation to CML-BP. De novo CML-BP occurred in 71 patients. Approximately 72% of patients received TKI therapy before CML-BP. The initial therapy for CML-BP included a TKI alone (35%), a TKI with chemotherapy (46%), and non-TKI therapies (19%). The median overall survival was 12 months and the median failure-free survival was 5 months. In multivariate analysis, myeloid immunophenotype, prior TKI, age ≥58 years, lactate dehydrogenase level ≥1227 IU/L, platelet count < 102 K/μL, no history of stem cell transplantation, transition to BP from chronic phase/accelerated phase, and the presence of chromosome 15 aberrations predicted for a significantly increased risk of death. Achievement of major hematologic response and/or complete cytogenetic response to first-line treatment was found to be predictive of better survival. The combination of a TKI with intensive chemotherapy followed by stem cell transplantation appeared to confer the best outcome.

Conclusions: Patients with CML-BP continue to pose a therapeutic challenge, have dismal outcomes, and require newer treatment approaches. Cancer 2017;123:4391-402. © 2017 American Cancer Society.

Keywords: blast phase (BP); bosutinib; chronic myeloid leukemia (CML); dasatinib; imatinib; nilotinib; ponatinib; tyrosine kinase inhibitors (TKI).

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Blast Crisis / diagnosis*
  • Blast Crisis / drug therapy*
  • Blast Crisis / mortality
  • Cohort Studies
  • Female
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality
  • Male
  • Middle Aged
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Risk Factors
  • Survival Analysis
  • Young Adult

Substances

  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases