Journal: Human vaccines & immunotherapeutics
This narrative review focuses on second primary cancers (SPCs) in survivors of hematologic malignancies.
Key points:
- Epidemiology: SPCs are increasingly common as patients live longer after treatment for leukemias, lymphomas, and related disorders. The review summarizes incidence patterns and risk profiles across different hematologic malignancies, though detailed rates are not provided in the abstract.
- Pathogenesis: SPC risk arises from multiple, interacting mechanisms:
- • Therapy-related effects: Cytotoxic chemotherapy, radiotherapy, and other treatments induce genomic instability that can drive secondary malignancies.
- • Clonal hematopoiesis: Treatment and age-related selective pressures promote expansion of mutated hematopoietic clones, which may predispose to subsequent cancers.
- • Immune dysregulation and inflammation: Chronic inflammatory signaling and impaired immune surveillance support oncogenesis.
- • Microenvironmental remodeling: Alterations in the bone marrow and surrounding microenvironment create a pro-tumor niche that may facilitate SPC development.
- Surveillance and biomarkers:
- • Current surveillance strategies are reviewed, including their limitations for early SPC detection in this population.
- • The review highlights emerging biomarkers and risk stratification tools designed to identify high-risk survivors earlier and more accurately.
- Emerging approaches:
- • Integrated multi-omics (genomics, transcriptomics, epigenomics, etc.) and tumor microenvironment profiling are proposed as ways to refine SPC risk assessment and monitoring.
- • Precision medicine strategies aimed at personalizing surveillance and potentially modifying treatment in initial hematologic malignancies to reduce long-term SPC risk are discussed.
- Future directions:
- • Strong emphasis on developing personalized surveillance programs tailored to individual treatment history, genetic risk, and microenvironmental features.
- • Need for translational validation of candidate biomarkers in prospective cohorts.
- • Advocacy for multidisciplinary management, integrating oncology, survivorship care, genetics, and primary care to mitigate SPC risk and improve long-term outcomes.