Use of a skin explant model for predicting GVHD in HLA-matched bone marrow transplants – effect of GVHD prophylaxis

Abstract

Summary:Over the last decade we have successfully evaluated the use of a human skin explant assay for predicting acute GVHD in HLA-matched sibling transplants. In the present study, we modified GVHD prophylaxis on an individual patient basis depending on the GVHD outcome predicted by the skin explant model. We have summarised our previous data describing how the skin explant assay results correctly predict GVHD occurrence and severity in 45/56 patients (80%); P Ͻ 0.0001, 2 19.97, df = 1. In a further cohort of 19 patients, all were predicted to develop grade II or above GVHD. These patients were given increased GVHD prophylaxis with the addition of methotrexate and a significant reduction in the expected incidence of GVHD was observed (P = 0.02; 2 7.7, df = 1; Fisher exact test P = 0.04). The results from these studies suggest that modifying GVHD prophylaxis, based on skin explant assay results, may reduce the expected incidence and severity of GVHD. We suggest that the technique might be used for selective GVHD prophylaxis in T cell non-depleted HLA matched sibling transplants.

Vitamin D receptor gene polymorphism associates with graft-versus-host disease and survival in HLA-matched sibling allogeneic bone marrow transplantation

“…GVHD prophylaxis consisted of 3 mg/kg cyclosporin A (CyA), either alone (n = 61) or together with other drugs (n = 27) for patients at higher risk of GVHD (determined by skin explant model 20 or by advanced recipient age and/or multiparous female donor with male recipient). Extra immunosuppression consisted of methotrexate 21 (MTX) in 17 patients; corticosteroids (CS) in four; anti-thymocyte globulin (ATG) in four; MTX and ATG in one; CS and ATG in one.…”

Skin biopsies for early diagnosis and prognosis of graft-versus-host disease in recipients of allogeneic stem cells from blood or bone marrow

“…[14][15][16][17][18][19][20] These studies indicate that skin biopsies have been of limited value to confirm or predict the development of systemic GVHD that requires steroid treatment. Our main objective was to investigate with histopathological and immunohistochemical methods whether the source of stem cells might influence the development of GVHD, and thus possibly acquire new insight into the mechanisms involved.…”

The detection of apoptosis in a human in vitro skin explant assay for graft versus host reactions

“…After seven days of culture, 4 mm patient skin biopsies were dissected and explants were added to responder lymphocytes at a concentration of 1 × 10 6 cells/well in complete medium with 10% autologous serum to the skin biopsy. 10 Control explants were incubated with medium alone or autologous lymphocytes alone.…”

“…8 Recent data also strongly suggest a target organ specificity of GVHD related tissue damage, 9 and that the main target cells for GVHD in the skin are keratinocytes. The basis of our investigation was to correlate keratinocyte apoptosis with the severity of graft versus host reactions (GVHR) in skin sections generated from an in vitro skin explant model used as an experimental model to study GVHR, and to predict GVHD in allogeneic stem cell transplants 10 (for a recent review see Sviland and Dickinson 11 ).…”