Second Myeloid Malignancies in a Large Cohort of Patients With Chronic Lymphocytic Leukemia: AÂ Single Institution Experience

Patients with chronic lymphocytic leukemia (CLL) have a 2- to 5-fold risk of developing a second malignancy compared with the general population. The incidence of myeloid malignancies, such as acute myeloid leukemia and myelodysplastic syndrome, is increased in CLL and has been linked to previous therapy. In this study, we aim at describing characteristics and determining risk factors for developing second myeloid disorders (SMDs) in patients with CLL. From a total of 1269 patients diagnosed with CLL during the study time period, 30 (2.4%) were found to have an SMD. The majority of SMDs were myelodysplastic syndrome or acute myeloid leukemia (76.7%). The median time from diagnosis of CLL to diagnosis of SMD was 4.47 years. Most patients who developed an SMD had received treatment for their CLL (86%). The median time from treatment of CLL to diagnosis of SMD was 4.19 years. The overall survival of patients with CLL with no second malignancy was significantly longer than those with an SMD (11.9 vs. 7.1 years, P = .001). There was no association between developing SMD and age, gender, expression of CD38, expression of ZAP-70, and unmutated immunoglobulin heavy chain gene status. The risk of developing SMD in our cohort was higher in patients who received fludarabine- or alkylator-based therapy. Our analysis is one of the largest series showing that patients receiving fludarabine or alkylator-based therapies for CLL have a higher risk of developing SMD. Our study also confirms previous reports that prognostic factors in CLL do not increase the risk for development of SMD. Clinicians should understand the leukemogenicity of fludarabine or alkylator-based treatments when considering treatments for patients with CLL.