Predictors of Response to Imatinib Therapy and Long-Term Outcomes in Paediatric and Adolescent Patients With Chronic Myeloid Leukaemia

预测儿童和青少年慢性粒细胞白血病患者对伊马替尼治疗的反应和长期预后的因素

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Abstract

BACKGROUND: Chronic myeloid leukaemia (CML) is an infrequent myeloproliferative neoplasm in the paediatric population as compared to adults. Despite vast progress in understanding the disease biology and therapy of CML-chronic phase (CML CP), the applicability of risk scoring systems in practice and prognostic factors in children remain grey areas. Hence, we tried to analyse disease characteristics, molecular response to frontline imatinib therapy and its clinical predictors along with long-term outcomes in our population. MATERIALS AND METHODS: In this study, we retrospectively analysed 104 paediatric patients aged ≤ 18 years, diagnosed with CML CP, treated at our centre between 2007 and 2024. Their baseline demographic profile, clinical characteristics, haematological parameters and molecular transcripts as diagnosed by RT-PCR were recorded. The follow-up response assessments, including haematological response, molecular response and long-term survival, were collected from medical records. Risk scores were computed and correlated with clinical outcomes. RESULTS: Our study included 104 paediatric patients presenting with CML CP. Splenomegaly was a universal feature with a median size of 10 cm below costal margin. The majority of patients belonged to the low-risk group according to Sokal, EUTOS and ELTS systems. Imatinib was initiated in all of them and was followed up for a median duration of 72 months. Overall, 95.2% patients achieved complete hematologic response (CHR) at 3 months. A total of 42.5% (43/101) patients achieved MMR at 12 months and 54.4% (55/101) patients achieved MMR at 18 months. Sokal scoring system and EMR at 3 months were significantly correlated with the achievement of MMR at 12 months. A total of 11 patients progressed to blast crisis and 10 patients expired in due course of the disease. The 2- and 10-year PFS was 96% and 82%, respectively. CHR at 3 months was significantly predictive of PFS. None of the scoring systems had predictive value for PFS. CONCLUSION: This is one of the largest reported data on Indian paediatric CML CP patients with long-term outcomes. The dynamics of adult CML, including risk scores, do not perfectly fit the scenario of paediatric patients. Hence, further studies and newer strategies are required for optimal management of paediatric CML patients.

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