Native Spleen Preservation During Visceral Transplantation Inhibits Graft-Versus-Host-Disease Development: Clinical and Experimental Study

Ann Surg. 2021 Jun 18. doi: 10.1097/SLA.0000000000004979. Online ahead of print.

Abstract

Objective: We aimed to assess whether native spleen preservation during VT affects GVHD incidence.

Summary background data: Graft-versus-host-disease (GVHD) is one of the most severe and frequently lethal hematological complications after visceral transplantation (VT) procedures. Because there is no specific treatment for GVHD, it is imperative to develop a strategy to reduce donor lymphocyte engraftment and proliferation.

Methods: Our study included both clinical and experimental data. A total of 108 patients were divided into three groups: a native spleen preservation group, a native spleen removal with no donor spleen group, and a donor spleen included (allogeneic spleen) group. We also used an allogeneic VT rat model, in which recipients were divided into two groups: a native spleen preservation (+SP) group and a native spleen removal (-S) group. Skin rash appearance, histopathological changes, chimerism, and spleen effects on circulating allogeneic T-cells were assessed.

Results: The patients with native spleen preservation showed a lower rate of GVHD (p < .001) and better survival (p < .05) than those in the other groups. Skin and histological signs of GVHD were lower in the rats in the +SP group (p < .05). The donor T-cell frequency in the bloodstream and skin was also significantly reduced when the native spleen was preserved (p < .01 and p < .0001, respectively).

Conclusions: The clinical and experimental data indicate that recipient spleen preservation protects against GVHD after VT, and donor cell clearance from the bloodstream by spleen macrophages could be the underlying mechanism. Therefore, spleen preservation should be considered in VT procedures, whenever possible.