CLL-153: Evaluation of Second Primary Cancer Risk Among Chronic Lymphocytic Leukemia Patients: Multicenter Study

Abstract

Context: Patients with chronic lymphocytic leukemia (CLL) have an increased risk of developing second primary cancers (SPC). Although cytogenetic disorders and some risk factors (such as ZAP 70, IGHC mutation) are held responsible, there is no definitive explanation for the increased cancer risk. Objective: Determining the frequency of SPC in CLL patients and determining the relationship between these cancers and the treatment status of CLL, cytogenetic factors, and other risk factors were the study aims. Design: The study was designed as a multicenter and retrospective study. The sample comprised 553 subjects with CLL diagnosis. Data collection commenced in August 2016 and was completed in May 2021. Results: Fifty-one of 553 patients followed for CLL had a history of SPC. The SPC development rate was 9.2%. The duration of CLL disease was 2.7 years, on average, at the time of SPC detection. Epithelial tumors were mostly observed. According to the incidence, the tumor types were skin, lymphoma, renal, breast, lung, gastrointestinal system, thyroid, malignant melanoma, prostate, Kaposi sarcoma, neuroendocrine tumor, ovarian, larynx, and salivary gland. The 13q deletion was the most common genetic abnormality in those who developed SPC, and the frequency of the 13q deletion was found to be increased significantly in those with malignancy compared to those without malignancy. Conclusion: In CLL patients with SPC, older age at diagnosis, 13q deletion, CD38 positivity, and treatment with fludarabine and monoclonal antibodies were found to be risk factors. We determined that SPC frequency increased independently from hemogram values, β2 microglobulin levels at diagnosis, the number of treatment lines, and genetic mutations other than 13q in CLL patients. In addition, the mortality rate was higher in CLL patients with SPC, and they were prone to be in advanced stages at the time of diagnosis. Patients with chronic lymphocytic leukemia (CLL) have an increased risk of developing second primary cancers (SPC). Although cytogenetic disorders and some risk factors (such as ZAP 70, IGHC mutation) are held responsible, there is no definitive explanation for the increased cancer risk. Determining the frequency of SPC in CLL patients and determining the relationship between these cancers and the treatment status of CLL, cytogenetic factors, and other risk factors were the study aims. The study was designed as a multicenter and retrospective study. The sample comprised 553 subjects with CLL diagnosis. Data collection commenced in August 2016 and was completed in May 2021. Fifty-one of 553 patients followed for CLL had a history of SPC. The SPC development rate was 9.2%. The duration of CLL disease was 2.7 years, on average, at the time of SPC detection. Epithelial tumors were mostly observed. According to the incidence, the tumor types were skin, lymphoma, renal, breast, lung, gastrointestinal system, thyroid, malignant melanoma, prostate, Kaposi sarcoma, neuroendocrine tumor, ovarian, larynx, and salivary gland. The 13q deletion was the most common genetic abnormality in those who developed SPC, and the frequency of the 13q deletion was found to be increased significantly in those with malignancy compared to those without malignancy. In CLL patients with SPC, older age at diagnosis, 13q deletion, CD38 positivity, and treatment with fludarabine and monoclonal antibodies were found to be risk factors. We determined that SPC frequency increased independently from hemogram values, β2 microglobulin levels at diagnosis, the number of treatment lines, and genetic mutations other than 13q in CLL patients. In addition, the mortality rate was higher in CLL patients with SPC, and they were prone to be in advanced stages at the time of diagnosis.