The interplay of clonal hematopoiesis and cancer: Clinical implications in oncology

Clonal hematopoiesis (CH) refers to the expansion of hematopoietic stem and progenitor cells carrying somatic mutations and is increasingly identified in oncology through cell-free DNA testing. Once regarded mostly as a precursor to myeloid neoplasms and a contributor to cardiovascular disease, CH is now recognized as a major determinant of clinical outcomes in patients with cancer. Specific anticancer agents selectively promote the expansion of clones with DNA damage response gene mutations, particularly those with TP53 or PPM1D mutations, which are strongly associated with myeloid neoplasms post cytotoxic therapy (MN-pCT). The extent of clonal growth varies with treatment and, in some cases, may regress once therapy is withdrawn. In addition to therapy-driven clonal selection, inflammatory stress accelerates clonal expansion, creating a self-reinforcing cycle that contributes to atherosclerosis and other inflammation-associated complications. In oncology, CH-derived immune cells can infiltrate the tumor microenvironment and remodel local immunity, influencing tumor growth and treatment response. This tissue-infiltrating form of CH, termed tumor-infiltrating CH, has been associated with inferior survival in some cancer cohorts. Together, these findings establish CH as both a clinical challenge and an opportunity in modern oncology. Dedicated CH clinics and molecular tumor boards are emerging to address its implications for risk stratification, treatment selection, and survivorship care. This review examines the biology and clinical impact of CH in oncology, including its mutational spectrum, clonal evolution, role in MN-pCT, effects on inflammation and the tumor microenvironment, and emerging strategies for risk assessment and patient management.