Long Term Survival of Chronic Myeloid Leukemia Patients with Chromosomal Aberrations in Philadelphia Negative Metaphases During Treatment with Tyrosine Kinase Inhibitors

Abstract

Additional clonal aberrations (ACAs) in Philadelphia negative metaphases of Chronic Myeloid Leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) were an early noticed event in the course of the treatment plan. However, their biological and clinical implications are not conclusive. In the present study, we investigated their incidence and impact on the prognosis and treatment response. Among 200 CML patients treated in our Department from 2002 to 2019, ACAs in Ph- cells were found in 21 (10.5%), with a median time from initiation of TKIs at 58 months. In addition to monosomy 7, trisomy 8 and loss of chromosome Y, we also identified other numerical and structural abnormalities including add(6)(q27), t(4;15)(q31;q26) t(2;10)(q23;q24), which have never been reported before. We noticed that the number of ACAs developed in Phcells is associated to the number of treatments before the initiation of TKIs. Probability of long-term overall survival at 15 years was 87.1%. Persistent clones were revealed in eight patients. As a result, our study indicates that Ph- ACAs do not impact the outcomes of CML. Aberrations such as monosomy 7 need close monitoring due to their association with increased risk of evolution to myelodysplastic syndrome or acute leukemia.