Second primary cancers following hematologic malignancies: Epidemiology, pathobiology and clinical management

Second primary cancers (SPCs) pose an increasingly significant clinical challenge for survivors of hematologic malignancies, attributed to improved therapeutic outcomes and prolonged survival. The development of SPCs is influenced by a complex interplay of treatment-related factors, genetic susceptibility, immune dysregulation, and microenvironmental remodeling. This narrative review summarizes the epidemiological patterns of SPCs in survivors of hematologic malignancies and discusses the underlying biological mechanisms, including therapy-induced genomic instability, clonal hematopoiesis, inflammatory signaling, and alterations in the bone marrow microenvironment. Furthermore, we review current surveillance strategies and emerging biomarkers for early detection and risk stratification. Additionally, we discuss the potential contributions of integrated multi-omics approaches, tumor microenvironment profiling, and precision medicine strategies to SPC monitoring and prevention. Lastly, we outline future directions for clinicians and researchers, emphasizing the necessity for personalized surveillance programs, translational biomarker validation, and multidisciplinary management strategies to mitigate SPC risk in long-term survivors.