Indicators of an increased risk of therapy-related myeloid neoplasms in lymphoma patients: how can we best evaluate severe impairment of bone marrow function?

The development of new lymphoma therapies in recent years has led to a significant increase in patient survival. However, in some cases, despite disease remission, the outcome of the applied therapy is diminished by the development of secondary cancers. These often have dismal outcomes and are unresponsive to standard therapies. Both therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML) are well-known side effects of cytotoxic chemotherapy and/or radiation therapy. This review summarizes the key factors associated with an increased risk of therapy-related neoplasms in lymphoma patients, focusing on the various elements that may contribute to this susceptibility. The major factors described in detail include the impact of different anti-lymphoma therapies, disturbances in the bone marrow microenvironment, the presence of clonal hematopoiesis, and germline predispositions. The review is based on a PubMed database search for articles published up to 1 May 2025, covering the abovementioned topics, as well as the authors' clinical and research experience. Considering the progress in lymphoma therapy and the prospect of long-term survival, efforts should be made to identify patients at higher risk of developing therapy-related myeloid neoplasms. A better understanding of germline predispositions and the role of clonal hematopoiesis should support therapy tailored to individual risk profiles.