T315I Mutation in Chronic Myeloid Leukemia: Clinicopathological Profile, Mutation Evolution, Treatment Response, and Clinical Outcomes

Background: The T315I BCR: ABL1 kinase-domain mutation represents an important mechanism of tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia (CML). Its pattern of emergence and association with treatment response and clinical outcomes remain clinically relevant. Material and Methods: This retrospective cohort study included 34 T315I-positive patients identified from a source cohort of 101 patients with imatinib-resistant CML. Demographic, clinicopathological, prognostic, molecular, treatment-response, and outcome data were evaluated. T315I mutation patterns were categorized as isolated/upfront, upfront with additional mutation, or sequential. Complete hematological response (CHR), major molecular response (MMR), blast-phase progression, and mortality were assessed. Results: The mean age was 40.50 ± 13.16 years, and 91.2% were male. At diagnosis, 82.4% were in chronic phase. High-risk disease was observed in 70.6%, 61.8%, and 64.7% according to Sokal, ELTS, and EUTOS scores, respectively. Isolated/upfront T315I was observed in 79.4%, upfront T315I with an additional mutation in 5.9%, and sequential T315I in 14.7%. The median time to mutation detection was 23.5 months. CHR was achieved in 67.6%, 91.2%, and 88.2% at 3, 6, and 12 months, respectively, while only 14.7% achieved MMR. During follow-up, 29.4% progressed to blast phase and 17.6% died. Small numbers of patients with sequential and additional-mutation patterns limited definitive comparisons between mutation subgroups. Conclusion: T315I-positive CML was characterized by adverse prognostic features, low molecular response, and clinically important rates of blast-phase progression and mortality. Most patients had isolated/upfront T315I, while sequential and additional-mutation patterns were less frequent. Timely mutation testing and close molecular monitoring remain important for guiding individualized therapy in TKI-resistant CML.

Keywords: Chronic myeloid leukemia, T315I mutation, BCR: ABL1, tyrosine kinase inhibitor resistance, mutation evolution, molecular response, blast-phase progression.