PROGNOSTIC VALUE OF ADDITIONAL CHROMOSOMAL ABERRATIONS IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA ON TYROSINEKINASE INHIBITORS THERAPY

Abstract

Prognostic significance of additional chromosomal abnormalities (ACAs) for tyrosinekinase inhibitors therapy (TKI) response in chronic myeloid leukemia (CML) patients is discussed. In many ways, this uncertainty is dueto the low frequency as well as the high variability of ACAs in patients with chronic phase CML. In this study, rate of this phenomenon and its impact on the resistance to TKI therapy in CML patients was evaluated. Overall, 502 (91.8%) patients had only the classic translocation t(9;22)(q34;q11) without ACAs at diagnosis. 45 (8.2%) patients presented with additional cytogenetic findings at diagnosis: 29 (5.3%) patients had variant translocations t(9;V;22), which were formed by three chromosomes, and in 16 patients (2.9%) had ACAs. One patient had both and was included in the group of patients with ACAs. The analysis of the tumor clone reduction dynamics by the Kaplan-Meier method did not reveal statistically significant differences in the cumulative complete cytogenetic and major molecular response rates (p = 0.712 and p = 0.111 respectively) between the patients with classical translocation t(9;22), patients with variant translocations and patients with ACAs. Analysis of long-term outcomes demonstrated inferior event-free (EFS), progression-free (PFS) and overall survival (OS) in CML patients with ACA at diagnosis. At 3 years, for patients with a classic translocation, patients with ACAs, and patients with a variant translocation t(9;V;22), the probability of EFS was 84,9% (95% ÑI, 81,2% – 88,6%), 93,8% (95% CI, 81,8% – 100,0%) and 43,9% (95% CI, 17,4% – 70,4%), respectively. The probability of PFS was 92,0% (95% Ѳ, 89,3% – 94,7%), 93,3% (95% Ѳ, 80,8% – 100,0%) and 60,6% (95% Ѳ, 35,9% – 85,3%), respectively. The probability of OS was 93,8% (95% C², 91,3% – 96,4%), 93,8% (95% C², 82,1% – 100,0%) and 76,2% (95% C², 65,2% – 87,2%), respectively. No statistical difference was observed between the patients with classic translocation t(9;22) and those with variant translocations in terms of EFS, PFS and OS. Chromosomal abnormalities that appeared in CML patients at diagnosis and are not classic CML-specific translocation t(9;22)(q34;q11) may impair the prognosis of disease outcome. The presence of variant transactions in diagnosis does not impact the TKI therapy effectiveness. Additional chromosomal abnormalities in Ph+ cells lead to loss of the achieved cytogenetic and/or molecular response, disease progression, and the overall survival reduction in CML patients, treated with TKI.

Keywords

• chromosomal aberrations
• chronic myeloid leukemia
• prognostic factors
• resistance
• tyrosine kinase inhibitors.