Clonal hematopoiesis and cardiovascular outcomes after hematopoietic cell transplantation: A systematic review and meta-analysis.

Abstract

e18578 Background: Clonal hematopoiesis (CH) is a known risk factor for cardiovascular disease, but its impact in cancer patients undergoing hematopoietic cell transplantation (HCT) is not well defined. We conducted a systematic review and meta-analysis to assess the association between CH and post-HCT cardiovascular outcomes. Methods: PubMed, Embase, Web of Science, and Cochrane were searched from inception to December 2025 for randomized control trials and observational studies evaluating cardiovascular outcomes after HCT. Eligible studies included adult patients undergoing HCT with sequence-defined CH, using gene panels and variant allele fraction (VAF) thresholds, that reported extractable post-transplant cardiovascular, cerebrovascular, or thromboembolic outcomes. We excluded case reports/series, reviews/abstracts without extractable data, animal or pediatric studies, non-oncologic transplant populations, studies without sequencing-confirmed CH or relevant outcomes, and overlapping cohorts. Adjusted and subdistribution hazard ratios were extracted and pooled using random effects meta-analysis using inverse weighting. Results: Of 2,187 studies, 5 studies, including both autologous and allogenic HCT recipients, were extracted from. The most frequently mutated genes were DNMT3A, TET2, ASXL1,TP53. In a pooled analysis of two independent autologous HCT cohorts, including multiple myeloma and lymphoma populations, CH was associated with increased risk of post-transplant heart failure (HR 3.24, 95% CI 2.02–5.19; I²=21%). In an autologous HCT survivorship cohort analyzed using competing-risk models, CH was associated with higher risks of coronary artery disease (sHR 2.22, 95% CI 1.06–4.64) and stroke (sHR 3.02, 95% CI 1.07–8.52). In an allogeneic HCT cohort with post-transplant deep sequencing, a higher CH mutation burden, defined as two or more CHIP mutations a variant allele fraction of 2% or more, was linked to an increased risk of incident atrial fibrillation (adjusted HR 4.05, 95% CI 1.17-14.04). Venous thromboembolism risk was higher, though not statistically significant after multivariable competing-risk adjustment (sHR 2.01, 95% CI 0.88–4.60). Conclusions: This meta-analysis demonstrates CH is associated with increased risk of adverse cardiovascular outcomes after HCT, supporting its potential cardiac biomarker, prior to HCT, and underscores the need for further prospective studies to further characterize cardiovascular surveillance in CH patients undergoing HCT to mitigate morbidity and mortality.