Thymus Transplantation for Chronic Graft Versus Host Disease

Graft-versus-host-disease (GVHD) is a common complication of allogeneic hematopoietic cell transplant (HCT). GVHD-related thymic damage results in a loss of thymic negative selection and further anti-host reactivity. GVHD has been classically divided into acute and chronic variants based upon the time of onset using a cutoff of 100 days. The overall incidence of GVHD remains between 30% and 60% and carries approximately a 50% mortality rate. We sought to assess whether thymus transplantation is able to restore thymic function and prevent the production of autoreactive T-cells. We performed bone marrow transplantation (BMT) on BALB/c mice with bone marrow cells from C57BL/6 (B6) mice using an established chronic GVHD model. Bone marrow cells from B6 mice given to the BALB/c mice were either T-cell depleted (control) or not (induced GVHD group/intervention group). Thymus from newborn, non-BMT BALB/c mice was inserted under the kidney capsule of the intervention group at 4 weeks post-BMT. We then clinically assessed whether thymus transplantation was able to prevent progression to chronic GVHD and increase survival. After 100 days BALB/c mice who received thymus transplant at 4 weeks had earlier reversal of clinical GVHD scores and earlier recovery of their body weight (n=14, p=0.008 and p=0.03 respectively). In addition, they showed an increased rate of survival vs GVHD induced control (75% vs 40% respectively,p=0.0043). This preliminary study suggests a novel approach using transplantation of recipient-type thymus at 4 weeks post-BMT may prevent the development of chronic GVHD and increase survival. Further studies are needed to replicate data and explore underlying mechanisms.