Impact of Bone Marrow Fibrosis on the Outcome of Chronic Myeloid Leukemia Treated with Second Generation Tyrosine Kinase Inhibitors

骨髓纤维化对采用第二代酪氨酸激酶抑制剂治疗慢性粒细胞白血病预后的影响

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Abstract

Chronic myeloid leukemia (CML) is characterized by the BCR-ABL1 fusion oncogene, leading to increased tyrosine kinase activity. The current study was aimed to evaluate the impact of bone marrow fibrosis on the clinical outcomes of CML patients treated with second-generation tyrosine kinase inhibitor(TKI) among patients in Pakistan. A longitudinal study was conducted at National Institute of Blood Disease and Bone Marrow Transplantation (NIBD-BMT), Karachi, from October 2022 to October 2023. A total of 150 CML patients aged 18-80 years receiving second generation TKI were included. BM fibrosis was graded according to WHO criteria. Outcomes such as complete hematological response (CHR) and major molecular response (MMR) were evaluated at 3 and 6 months. Data were analyzed using SPSS version 25, with p-value of < 0.05. The median age of patients was 43.5 years, with male predominance (60.7%). BM fibrosis was present in 69.3% of patients at diagnosis. Patients with lower fibrosis grades (MF 0-1) had significantly higher rates of CHR at 3 months (73.5%) and MMR at 6 months (64.7%) compared to those with higher grade fibrosis (MF 2-3) with CHR of 66.7% and MMR of 50%. Optimal response rates were also higher in lower fibrosis grades (77.4% vs. 56.2%). Moreover, treatment failure was common with higher fibrosis grade. BM fibrosis is a critical factor influencing the response to TKIs in CML patients. Lower grades of fibrosis correlate with higher response rates and better clinical outcomes, suggesting the importance of early intervention and tailored treatment approaches based on fibrosis grading.

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