Clonal Hematopoiesis in Solid Tumor Survivors: A Retrospective Literature Review on an Emerging Precursor to Therapy-Related Hematologic Malignancies

Document Type

Conference Proceeding

Publication Date

9-2025

Publication Title

Clinical Lymphoma, Myeloma and Leukemia

Abstract

Context: Clonal hematopoiesis (CH), defined as the expansion of hematopoietic stem or progenitor cells harboring somatic mutations in the absence of cytopenias or hematologic malignancy, has recently emerged as a significant biomarker of future myeloid transformation. It is most commonly age-associated but is also increasingly recognized in patients exposed to cytotoxic cancer therapies. In solid tumor survivors, CH may reflect subclinical genomic stress resulting from radiation, platinum-based chemotherapy, or immunotherapy and is believed to increase the risk of therapy-related myeloid neoplasms, particularly myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Objective: Evaluate the prevalence, mutation profile, clinical significance, and progression risk of CH in adult survivors of solid tumors. Design: Retrospective literature review. PubMed, EMBASE, and Scopus were searched (2000–2025) using relevant terms. Inclusion criteria were cohort or registry studies involving adult patients with solid tumors and reporting on CH prevalence, mutation types, and outcomes. Setting: Multi-institutional cancer centers, large genomic profiling databases (eg, MSKIMPACT, Foundation Medicine, UK Biobank), and prospective registry cohorts. Participants: Solid tumor survivors aged ≥18 years with post-treatment sequencing data or follow-up for secondary hematologic malignancies. Cancer types included lung, breast, prostate, bladder, and testicular. Interventions: Prior exposure to systemic chemotherapy (eg, platinum agents, etoposide), radiation therapy, or immune checkpoint inhibitors. Main Outcome Measures: Prevalence of CH, dominant mutations (TP53, PPM1D, DNMT3A, TET2), time to therapy-related MDS/AML, and risk factors for clonal expansion. Results: CH was present in 10– 25% of solid tumor survivors, with higher rates in older individuals and those exposed to chemotherapy or radiation. Therapy-associated CH mutations, especially TP53 and PPM1D, were enriched in patients treated with platinum agents and radiation. In some studies, pre-existing CH mutations predicted subsequent therapy-related MDS/AML with a hazard ratio of up to 12. Higher variant allele frequency (VAF ≥2%) and multiple co-mutations were associated with faster progression. No guidelines currently exist for CH surveillance. Conclusions: CH is common in solid tumor survivors and can act as a molecular harbinger of hematologic malignancy. Surveillance of high-risk mutations and integration of CH monitoring into survivorship care warrants prospective evaluation to mitigate late-onset hematologic toxicity.

Volume

25

Issue

Suppl 1

First Page

S641

Comments

Society of Hematologic Oncology Thirteenth Annual Meeting, September 3-6, 2025, Houston, TX

Last Page

S641

DOI

10.1016/S2152-2650(25)02077-4

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