Secondary myelodisplasia (MDS) and acute myeloide leukaemia (AML) are frequent long term complications in Chronic Lymphocytic Leukemia (CLL) and Waldesntrom Macroglobulinemia (WM) patients. Although disease-related immune-suppression plays a crucial role in leukemogenesis there is great concern that therapy may further increase the risk of developing these devastating complications.
Nucleoside analogs (NA) and alkilator agents are considered appropriate agents in the treatment of both CLL and WM patients. Prolonged immunosuppression related to nucleoside analogs therapy and the incorporation of these agents or their metabolites into DNA, with potentially mutagenic action, leads to speculation that their therapeutic use might be responsible for an increased incidence of second cancer especially when combined with other DNA damaging agents like alkylators. In this review the published studies considering the occurrence of secondary MDS and AML in CLL and WM patients are reported and the potential role of chemotherapeutic agents in leukemogenesis is discussed.