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

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.