title: An in vitro skin explant assay as a predictive assay for graft-versus-host disease in a cohort of pediatric transplants.
abstract: Severe acute graft-versus-host disease (GvHD) remains a serious complication of allogeneic stem cell transplantation. An in vitro skin explant assay was used to predict the occurrence and severity of acute GvHD in a cohort of 30 pediatric patients undergoing human leucocyte antigen (HLA)-matched sibling transplants (20 patients) and matched or one antigen mismatched unrelated donor transplants (10 patients). In the cohort of HLA-matched sibling transplants, the result appeared to reflect the degree of GvHD prophylaxis. The skin explant assay correlated with GvHD outcome in 12 of 20 children, but this did not reach statistical significance (chi-square 0.95, d.f.=1, p=0.32). These results support previous observations. In this present cohort, patients were treated either with cyclosporin A (CsA) monotherapy (n=7) or with CsA plus additional methotrexate (MTX) (n=13). We have previously demonstrated that the skin explant assay was not as predictive in patients receiving CsA plus additional MTX compared to cohorts treated with CsA alone. In the group of patients treated with CsA alone, four of five patients (80%) predicted to develop GvHD developed acute GvHD of grade II or above; of two patients predicted to develop only grade 0-I GvHD, one patient developed no GvHD and the other grade II GvHD. In the CsA plus MTX group, nine patients were predicted to develop GvHD. Five of nine (55%) developed acute GvHD of grade II or above, while three of four with grade 0 or I skin explant assay results developed only grade 0-I GvHD. In a cohort of 10 patients who received unrelated donor transplants, the skin explant assay correlated with GvHD outcome in all 10 patients (Fisher's exact test p=0.008). Hence, the skin explant assay is a pretransplant in vitro GvHD predictive test that predicts the occurrence and severity of acute GvHD in pediatric unrelated donor transplants and to varying degrees, depending on the GvHD prophylaxis protocols, in HLA-matched sibling cohorts.
authors.affiliation: 2nd Pediatric Clinic, University Hospital Motol, V Uvalu 84, 150 18 Prague 5, Czech Republic. ilona.hromadnikova@lfmotol.cuni.cz
authors.forename: I
authors.initials: I
authors.lastname: Hromadnikova
authors.forename: P
authors.initials: P
authors.lastname: Sedlacek
authors.forename: J
authors.initials: J
authors.lastname: Stary
authors.forename: M
authors.initials: M
authors.lastname: Cermakova
authors.forename: J
authors.initials: J
authors.lastname: Vavrinec
authors.forename: K
authors.initials: K
authors.lastname: Stechova
authors.forename: L
authors.initials: L
authors.lastname: Dolezalova
authors.forename: L
authors.initials: L
authors.lastname: Sviland
authors.forename: A M
authors.initials: AM
authors.lastname: Dickinson
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D046508:Culture Techniques; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015994:Incidence; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012867:Skin / Q000276:immunology* / Q000473:pathology; D014181:Transplantation Immunology
chemical_list: D006680:HLA Antigens