Second primary malignancies in non-Hodgkin lymphoma: epidemiology and risk factors.

With the advancements in therapeutics for non-Hodgkin lymphoma (NHL), the long-term survival of patients with NHL has markedly increased. Second primary malignancies (SPMs) have become an increasingly relevant long-term concern for NHL survivors. The etiology of SPMs is multifactorial and involves multiple steps. Germline alterations, immune dysregulation, and clonal hematopoiesis contribute to the accumulation of intrinsic adverse factors, and external factors such as lifestyle; exposure to infectious factors; and late effects of radiotherapy, chemotherapy, high-dose therapy, and autologous hematopoietic stem cell transplantation further increase SPM risk. Therapy-related myeloid neoplasms (t-MNs) are a devastating complication of cytotoxic chemotherapeutic agents. However, as targeted therapies begin to replace cytotoxic chemotherapy, the incidence of t-MNs is likely to decline, particularly for indolent B-cell NHL.