Increased Incidence of Clonal Hematopoiesis in Lung Transplant Recipients Involves DNA Damage Response Genes

Lung transplant recipients receive lifelong immunosuppression that includes a calcineurin inhibitor (tacrolimus or cyclosporine), an anti-proliferative agent (mycophenolate or azathioprine) and corticosteroids. They are also known to be at increased risk for a broad spectrum of adverse hematologic events. This includes relatively common complications such as neutropenia and other cytopenias, which occur in over half of patients, as well as rarer events such as de novo hematopoietic malignancy. Certain patterns of clonal hematopoiesis, the expansion of unique somatic clones in hematopoietic stem cells, are known to be associated with cytotoxic therapy and the development of hematologic malignancies. We hypothesized that the stress of transplantation and subsequent immunosuppression provides an environment whereby a unique pattern of clonal hematopoiesis emerges.