Recovery of Patient Peripheral Blood Mononuclear Cells after Treatment with Protease Inhibitor in Post-transfusion Graft-versus-host Disease.

Abstract

Post-transfusion graft-versus-host disease (PT-GVHD) is a fatal adverse effect of blood transfusion.1)-3) The mortality rate is said to be 99% or higher.4) In spite of the seriousness of the disease, no definitively effective drug for curing patients of it has been identified. Recently, however, we reported on the potential usefulness of a protease inhibitor, nafamostat mesilate (NM), for treatment of PT-GVHD.5), 6) This potential usefulness of NM was suggested by the results in vitro experiments in which possible PT-GVHD effector cytotoxic T cell (CTL) clones and tumor necrosis factor β (TNF β) producing T cell clones established by us were used.7), 10) NM inhibited the cytotoxicity of the CTL clones and TNF β production by the TNF β producing clones.6) Based on these results, NM was administered to two patients with PT-GVHD. NM administration resulted in marked recovery of the patient peripheral blood mononuclear cell (PBMC) detected by microsatellite DNA polymorphism analysis distinguishable between donor and patient PBMCs. This is the first report of the marked recovery of PT-GVHD patient PBMC from very low ones which were replaced almost all with donor PBMCs. Moreover, NM administration was associated with body temperature normalization, disappearance of a body rash, liver function improvement and an unusual long survival time after onset of PT- GVHD in both cases. NM is potentially useful drug for treatment of PT-GVHD.