Clinical characteristics, disease evolution and survival in patients with chronic myeloid leukemia, BCR-ABL1 (+) and T315I mutation

Introduction: The T315I mutation in patients with chronic myeloid leukemia (CML) has been associated with therapeutic resistance and an unfavourable prognosis. Aim: To study the frequency of T315I mutation in patients with CML, BCR-ABL(+), their clinical characteristics, disease evolution, and median survival. Patients and methods: We studied 75 patients with CML and BCR-ABL1(+). T315I mutation was detected by digital droplet PCR and BCR-ABL1 was analyzed by RT-PCR. A comparative analysis was performed by sex, age, disease phase, risk group, treatment, molecular response (MR), and median survival in T315I(+) and T315I(−) patients. Results: T315I mutation was detected in 11 patients (14.7%). No significant difference was found in the phase, risk group, and first-line therapy. A significantly higher proportion of T315I(+) did not achieve MR>3.5 log: 8 (72.7%) vs. 22 (34.4%) (p=0.023). The lowest mean BCR-ABL1 levels were significantly higher in the CML T315I(+) group compared to the CML T315I(−) group: 12.1±6.0 vs. 3.77±1.28 (p=0.009). The median survival of T315I(+) patients was significantly shorter: 73 months vs. 175 months (p Conclusions: Our data confirm the world experience on the frequency of T315I mutation, including the unfavourable evolution, resistance to TKI treatment and short survival. ddPCR is a highly sensitive method for early detection of genetic mutations which gives the chance for effective treatment.