Management of pre-treatment comorbidities andtyrosine kinase inhibitor use in patients with chronicphase chronic myeloid leukemia

The aim of this study was to determine the frequency and distribution of pretreatment comorbidities in patients with chronic-phase chronic myeloid leukemia (CML), to evaluate their impact on tyrosine kinase inhibitor (TKI) selection and treatment course, to identify the management of treatment-related adverse effects, and to assess the influence of comorbidities on survival outcomes. This retrospective, single-center study included 121 patients diagnosed with chronic- phase CML and followed at Trakya University Faculty of Medicine between January 2005 and September 2024. Demographic, laboratory, and genetic data, comorbidities, treatment lines, adverse events, and outcomes were retrieved from patient records. Comorbidities were assessed using the Charlson Comorbidity Index (CCI). Data were analyzed with SPSS v22.0. Statistical comparisons were made using chi-square, Student's t, Mann-Whitney U, and Kruskal-Wallis tests. Survival analyses were performed using Kaplan-Meier and Cox regression methods, with p<0.05 considered significant. The median age was 57 years, and 57.9% of patients were male. At diagnosis, 80.17% had at least one comorbidity; the median CCI score was 2 (range 0–6), and the median number of comorbidities was 2 (range 0–11). The most common comorbidity systems were cardiovascular (63.6%), endocrine (38.8%), and respiratory (28.9%). First-line therapy consisted primarily of imatinib (62.8%), followed by nilotinib (16.5%), dasatinib (5.8%), bosutinib (11.6%), and ponatinib (3.3%). Second-line therapy was required in 37.2% of patients, mainly due to drug resistance (82.2%). Over 91% of patients in the second and third lines had at least one comorbidity. The mortality rate was 19%; deaths were significantly more frequent among patients with comorbidities (p=0.043). The mean overall survival was 190.8 months, being shorter in those with comorbidities (181.8 vs. 200 months, p=0.040). Cardiovascular (p=0.003), respiratory (p=0.017), and urinary (p=0.035) comorbidities adversely affected survival. Cox regression analysis identified high CCI score, greater number of comorbidities, and shorter first-line therapy duration as independent poor prognostic factors. Pretreatment comorbidities are highly prevalent among chronic-phase CML patients and significantly affect survival, particularly cardiovascular and respiratory disorders. Comorbidity burden should be carefully considered in TKI selection and treatment management. Higher CCI score and increased comorbidity count are independent predictors of poorer outcomes. Thorough assessment and individualized treatment strategies are essential for optimizing survival and reducing mortality. Keywords: chronic myeloid leukemia; tyrosine kinase inhibitor; comorbidity