Risk of secondary chronic myeloid leukemia in cancer survivors: A nationwide population-based study in Taiwan

Abstract Background. Secondary chronic myeloid leukemia (CML) is a rare but serious late complication in cancer survivors. Despite its clinical relevance, population-based evidence regarding its incidence and risk factors across different solid tumor types remains limited. This study aimed to investigate the risk and clinical predictors of secondary CML using Taiwan's National Health Insurance Research Database. Material and methods. We conducted a retrospective cohort study using data from the Taiwan National Health Insurance Research Database (NHIRD) and Taiwan Cancer Registry between 2000 and 2021. Patients with a primary malignancy were identified and followed longitudinally for the development of CML. Exclusion criteria included age under 18 years, missing demographic data, primary hematologic malignancies, and metastatic or unknown primary cancer types. The primary outcome was the development of secondary CML, defined by diagnosis confirmed through disease-specific molecular or cytogenetic testing (e.g., RT-PCR, RQ-PCR, or chromosomal translocation analysis) and subsequent treatment with a tyrosine kinase inhibitor. Cox proportional hazards models were used to identify clinical risk factors associated with secondary CML. Results. A total of 1,564,947 patients were included, with a median age of 63 years (range 18–121), and 53.9% were male. The most common comorbidities were dyslipidemia (70.0%), hypertension (54.4%), pulmonary hypertension (47.1%), and diabetes mellitus (34.0%). The most frequent cancer types were gastrointestinal (38.6%), respiratory (13.5%), breast (13.5%), and head and neck (10.7%). During the follow-up period, 191 patients developed secondary CML, with an overall incidence of 2.55 per 100,000 person-years. The highest incidence rates (per 100,000 person-years) were observed in central nervous system (4.34), endocrine (3.71), urinary tract (3.39), and GI cancers (3.39). Among cancer subtypes, pancreas (5.28), gallbladder and extrahepatic bile ducts (5.04), and liver/intrahepatic bile duct cancers (4.77) had the highest rates. In univariate analysis, significant risk factors included male sex (hazard ratio [HR] 2.01), age ≥ 65 years (HR 1.29), atrial fibrillation (HR 2.08), autoimmune disease (HR 1.63), liver cirrhosis (HR 1.92), chronic obstructive pulmonary disease (HR 1.32), cerebrovascular accident (HR 1.42), diabetes mellitus (HR 1.75), heart failure (HR 2.21), hypertension (HR 1.59), and pulmonary hypertension (HR 1.40). Multivariate analysis identified male sex (HR 1.96; 95% confidence interval [CI] 1.45–2.64; p < 0.001), diabetes mellitus (HR 1.46; 95% CI 1.07–2.01; p = 0.018), and heart failure (HR 1.74; 95% CI 1.10–2.76; p = 0.018) as independent predictors.Conclusion. In this population-based cohort, specific solid tumors such as pancreatic and hepatobiliary cancers were associated with a relatively higher incidence of secondary CML. Male sex, diabetes, and heart failure were independently associated with increased risk. These findings support long-term hematologic surveillance in high-risk cancer survivors.