3 years ago

Clonal chromosomal abnormalities appearing in Philadelphia negative metaphases during CML treatment.

Rios MB, Garcia-Manero G, Kantarjian H, Sasaki K, Nogueras Gonzalez G, Kadia T, Ravandi F, Tang G, Borthakur G, Ferrajoli A, Wierda W, Jabbour E, Patel K, Issa GC, Dellasala S, Short NJ, Cortes JE, Luthra R
Clonal chromosomal abnormalities in Philadelphia chromosome-negative metaphases (CCA/Ph-) emerge as patients with chronic phase chronic myeloid leukemia (CP-CML) are treated with tyrosine kinase inhibitors (TKI). We assessed the characteristics and prognostic impact of 598 patients with CP-CML treated on clinical trials with various TKIs. CCA/Ph- occurred in 58 patients (10%) and the most common were - Y in 25 (43%) and trisomy 8 in 7 patients (12%). Response to TKI therapy was similar for patients with CCA/Ph- and those without additional chromosomal abnormalities (ACAs). We further categorized CCA/Ph- into those where - Y was the only clonal abnormality, and all others. We found that patients with non -Y CCA/Ph- had worse failure-free survival (FFS), event-free survival (EFS), transformation-free survival (TFS) and overall survival (OS) compared to those without ACAs with the following 5-year rates: FFS (52% vs 70%, P=0.02), EFS (68% vs 86%, P=0.02), TFS (76% vs 94%, P <0.01) and OS (79% vs 94%, P=0.03). In a multivariate analysis, non -Y CCA/Ph- increased the risk of transformation or death when baseline characteristics were considered with a hazard ratio (HR) of 2.81 (95% CI 1.15-6.89, P=0.02). However, this prognostic impact was not statistically significant when achieving BCR-ABL <10% at 3 months was included in the analysis. In conclusion, non -Y CCA/Ph- are associated with decreased survival when emerging in patients with chronic phase CML across various TKIs.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28835440

DOI: PubMed:28835440

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