Secondary Malignancies in Patients with Chronic Lymphocytic Leukemia: A Single-Center Real-World Experience

CLL in Secondary Malignancies

Abstract

Background: Patients with chronic lymphocytic leukemia (CLL) have an increased risk of developing secondary malignancies due to disease-related immune dysregulation, treatment-associated immunosuppression, and advanced age. However, real-world data regarding the incidence and characteristics of secondary malignancies in CLL remain limited. This study aimed to evaluate the incidence, clinical characteristics, and distribution of secondary malignancies in patients with CLL.
Methods: This retrospective single-center study included 308 patients diagnosed with CLL between January 2010 and December 2024. CLL diagnosis was established by flow cytometric immunophenotyping, and all secondary malignancies were confirmed histopathologically by tissue biopsy. Demographic characteristics, disease stage, immunophenotypic findings, cytogenetic abnormalities, and secondary malignancy types were analyzed.
Results: Among 308 patients with CLL, 21 patients (6.8%) developed secondary malignancies during follow-up. The mean age of these patients was 71 years, and 16 (76.2%) were male. The most common secondary malignancies were skin cancer (n=6, 28.6%) and lung cancer (n=6, 28.6%), followed by bladder cancer (n=5, 23.8%), breast cancer (n=2, 9.5%), prostate cancer (n=1, 4.7%), and rectal cancer (n=1, 4.7%). Most patients (76.2%) were classified as Rai stage 1–2 at the time of CLL diagnosis. Although 17p deletion was detected in approximately 15% of the overall CLL cohort, it was identified in only one patient (4.7%) who developed a secondary malignancy.
Conclusion: Secondary malignancies represent a clinically significant complication in patients with CLL, occurring in approximately 6.8% of cases in our cohort. Skin and lung cancers were the most frequently observed malignancies. The predominance of secondary malignancies among older patients and those with early-stage disease suggests that immune dysregulation associated with CLL may contribute to carcinogenesis independently of disease burden. Long-term surveillance and appropriate cancer screening strategies should be considered an integral component of CLL follow-up.