Solid Organ Transplant Recipients Exhibit More TET2-Mutant Clonal Hematopoiesis of Indeterminate Potential Not Driven by Increased Transplantation Risk

Abstract

Abstract Purpose: Solid organ transplant recipients comprise a unique population of immunosuppressed patients with increased risk of malignancy, including hematologic neoplasms. Clonal hematopoiesis of indeterminate potential (CHIP) represents a known risk factor for hematologic malignancy and this study describes the prevalence and patterns of CHIP mutations across several types of solid organ transplants. Experimental Design: We use two national biobank cohorts comprised of >650,000 participants with linked genomic and longitudinal phenotypic data to describe the features of CHIP across 2,610 individuals who received kidney, liver, heart, or lung allografts. Results: We find individuals with an allograft before their biobank enrollment had an increased prevalence of TET2 mutations (OR, 1.90; P = 4.0e−4), but individuals who received transplants post-enrollment had a CHIP mutation spectrum similar to that of the general population, without enrichment of TET2. In addition, we do not observe an association between CHIP and risk of incident transplantation among the overall population (HR, 1.02; P = 0.91). And in an exploratory analysis, we do not find evidence for a strong association between CHIP and rates of transplant complications such as rejection or graft failure. Conclusions: These results demonstrate that recipients of solid organ transplants display a unique pattern of clonal hematopoiesis with enrichment of TET2 driver mutations, the causes of which remain unclear and are deserving of further study.