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Abstract Background Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that harbors the Philadelphia chromosome. Tyrosine kinase inhibitor (TKI) therapy has dramatically improved the survival of patients with CML. Nevertheless, 20%–40% of CML patients require changes in TKI therapy due to intolerance or drug resistance. A total of 30%–60% of resistant cases result from kinase domain (KD) mutations. There is currently no published data on CML KD mutations in South Africa. Methods This retrospective, descriptive study collected data from 206 CML patients attending the King Edward Hospital Hematology clinic. Patient‐based and mutation‐based factors were analyzed using descriptive statistical analysis and Kaplan–Meier curves for survival analysis. Results KD mutations were detected in 29.1% (n = 60 of 206). A total of 40 different KD mutations were detected, with unknown responses to TKI therapy in 65% (n = 26 of 40). A total of 57.7% (n = 15 of 26) of mutations with an unknown response, showed a response to specific TKIs in our study. Four patients had A399T mutations, of which two showed good responses to Nilotinib. Patients with I293N and V280M mutations showed good responses to Imatinib. G250E was most frequently detected. Despite M351T being one of six most commonly reported KD mutations globally, this mutation was not detected in our patient cohort. A total of 20.9% (n = 43 of 206) human immunodeficiency virus (HIV) positive patients were identified, of which 25.6% (n = 11 of 43) had KD mutations. HIV status showed no significant effect on mutational status or overall survival. Conclusion The predicted response to TKI therapy was unknown in more than half of the KD mutations detected in our patient population. Additionally, eight patients with mutations with known responses to TKIs showed responses discordant to that expected. HIV status and KD mutations had no statistically significant effect on overall survival. Although some data were comparable to international publications, few notable differences warrant further investigation.

Introduction. Chronic myeloid leukaemia (CML) management has evolved from a disease once considered to be incurable just over 2 decades ago to that of one of a “functional cure” as defined by the sustained molecular response on stopping tyrosine kinase inhibitor(TKI) therapy. The next goal of CML management has been treatment-free remission (TFR). The past 4 years have seen much international data on TFR attempts in CML in clinical practice. However, Africa as a continent has lagged behind the rest of the world, in keeping up with the latest trends in CML management, and so this study aims to address this gap by assessing the outcome of TFR in CML in a single centre in South Africa (SA). Methods. We conducted a retrospective cohort study in 12 CML patients in the chronic phase to assess the success of TKI discontinuation. The patients were treated in King Edward VIII Hospital (KEH), a tertiary, academic hospital in KwaZulu-Natal, South Africa, and the study period was from June 2020 to May 2022. Patients included had to have been on TKI therapy for a minimum of 5 years and achieved a deep molecular response (DMR) for a minimum period of 3 years. Results. The overall TFR cohort showed a success rate of 75% at a median follow-up of 12 months. All patients who failed TFR, defined as a loss of major molecular remission (MMR), failed within 6 months of stopping TKI therapy. All patients who failed TFR regained DMR after retreatment with TKI, with no disease progression reported. The only factor influencing the success of TFR was the total period of TKI therapy. Conclusion. Despite our study having a small cohort of patients, this study demonstrated that TFR in CML is an attainable goal, even in a resource-limited setting.