Occurrence of chromosomal abnormalities in Philadelphia chromosome-negative metaphases in patients with chronic-phase chronic myeloid leukemia undergoing TKI treatments

Leuk Lymphoma. 2019 Dec;60(14):3503-3511. doi: 10.1080/10428194.2019.1636984. Epub 2019 Jul 8.

Abstract

Forty-three chromosomal abnormalities in Philadelphia-negative metaphases (Ph-CAs) appeared in 35 of 432 patients in chronic phase chronic myeloid leukemia (CP-CML) undergoing tyrosine kinase inhibitor (TKI) treatments. These CAs were mostly common in trisomy-8 (16 cases), trisomy-Y (five cases), and monosomy-7 (five cases). Furthermore, Ph- CAs were significantly associated with higher platelet count (494 × 109/L vs. 326 × 109/L, p = .006), and higher incidence of true clonal evolution in Ph-positive metaphase (22.9% vs. 9.1%, p = .017). Additionally, patients with Ph- CAs had worse rates of complete cytogenetic remission (76% vs. 86%, p = .0091), major molecular remission (55% vs. 76%, p = .001), progression-free survival (47% vs. 86%, p < .001), but a similar overall survival rates compared to those in patients without Ph- CAs. In conclusion, Ph- CAs may predict worse response to TKI therapies and survival in patients with CP-CML, thus requiring close cytogenetic monitoring.

Keywords: Chronic myeloid leukemia; Philadelphia chromosome-negative metaphases; monosomy-7 and del(7q); prognosis; tyrosine kinase inhibitors.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Chromosome Aberrations / chemically induced*
  • Cytogenetic Analysis
  • Female
  • Follow-Up Studies
  • Humans
  • Leukemia, Myeloid, Chronic-Phase / drug therapy
  • Leukemia, Myeloid, Chronic-Phase / genetics*
  • Leukemia, Myeloid, Chronic-Phase / mortality*
  • Leukemia, Myeloid, Chronic-Phase / pathology
  • Male
  • Metaphase*
  • Middle Aged
  • Philadelphia Chromosome*
  • Prognosis
  • Protein Kinase Inhibitors / adverse effects*
  • Retrospective Studies
  • Survival Rate
  • Young Adult

Substances

  • Protein Kinase Inhibitors