Skin Explant Assay – an in vitro Graft versus Host Disease PredictiveTest for Allogeneic Haematopoietic Stem Cell Transplantation

Overview

Background.
Acute graft versus host disease (GvHD) remains a severe complication of allogeneic haematopoieticstem cell transplantation (HSCT). Our study summaries results of skin explant assay (SEA) as a pretransplant GvHDpredictive test in a cohort of paediatric (n=33) and adult (a=8) patients receiving grafts from their HLA identicalsiblings (n=28), haploidentical relatives (n=3) and unrelated donors (n=10). Results GvHD prediction are correlatedwith the occurence and severity of acute GvHD posttransplant and effect of GvHD prophylaxis on GvHD clinicaloutcome is evaluated.Methods and Results. SEA utilises responding lymphocytes of the donor, which are sensitized firstly in vitro bymononuclears cells of patient in allogeneic mixed lymphocyte culture (MLC) and subsequently co-cultured withrecipient´s skin. Histopathological changes found in patients´ skin explants are evaluated according to standardLerner classification for acute GvHD. In general, GvHD predictive results in SEA correlated with GvHd clinicaloutcome in 28 out of 41 tested patients (68 %, p=0.015). In a cohort of HLA identical sibling transplants GvHDpredictive results correlated with clinical manifestation of acute GvHD only in 15 out of 28 patients on individualGvHD prophylaxis. GvHD prophylaxis in the form of cyclosporine A (CsA) combined with short-term methotrexate(MTX) reduced the risk of acute GvHD in 10 out of 14 transplated patients (71 %) meanwhile CsA alone prophylaxisonly in 1 out of 5 patients (20 %). In a cohort of unrelated pairs on CsA/MTX prophylaxis combined with horseanti-lymphocyte globuline (ALG) correlated the GvHD prediction with GvHD clinical outcome (100 %, p=0.003).In all patients transplanted with the grafts from their haploidentical relatives the occurence of severe GvHD waspredicted.Conclusion. Skin explant assay helps identify pretransplant patients at higher risk of severe acute GvHD. GvHDpredictive results enable the transplantation team to individualise GvHD prophylaxis and to optimise selection ofthe donor.

Key words:
graft versus host disease, skin explant assay, bone marrow transplantation