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Glutathione S ‐transferase A1 polymorphisms and acute graft‐vs.‐host disease in HLA‐matched sibling allogeneic hematopoietic stem cell transplantation
Author(s) -
Kim Inho,
Keam Bhumsuk,
Lee KyungHun,
Kim Jin Hee,
Oh So Yeon,
Ra Eun Kyung,
Yoon SungSoo,
Park Sung Sup,
Kim Chul Soo,
Park Seonyang,
Hong YunChul,
Kim Byoung Kook
Publication year - 2007
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/j.1399-0012.2006.00624.x
Subject(s) - medicine , human leukocyte antigen , hematopoietic stem cell transplantation , graft versus host disease , sibling , immunology , transplantation , stem cell , glutathione s transferase , disease , genetics , glutathione , pathology , antigen , enzyme , biology , psychology , developmental psychology , biochemistry
Busulfan and the metabolites of cyclophosphamide are conjugated with glutathione and catabolized by enzymes of the cytosolic glutathione S ‐transferases family. There are clearly linked single nucleotide polymorphisms in the promoter region of the glutathione S ‐transferase A1 gene (i.e., GSTA1*A , −567T, −69C and −52G; GSTA1*B , −567G, −69T and −52A). We assessed whether the clinical outcomes, including acute graft‐vs.‐host disease, of 61 patients with hematological malignancies, following HLA‐matched sibling allogeneic stem cell transplantation using busulfan/cyclophosphamide conditioning are altered by glutathione S ‐transferase A1 genotypes. Globally, grade II–IV acute graft‐vs.‐host disease developed in 13 patients (21%). Grade II–IV acute graft‐vs.‐host disease developed in 15.2% of 46 patients with GSTA1*A/*A diplotype and in 40.0% of 15 patients with GSTA1*A/*B or GSTA1*B/*B diplotype (p = 0.04). Moreover, this relationship between GSTA1*A/*A diplotypes and lower incidence of acute graft‐vs.‐host disease was independent of the age, gender, stem cell source, and disease status. The incidences of acute skin graft‐vs.‐host disease were 7% (3/46) in patients with GSTA1*A/*A and 27% (4/15) in patients without GSTA1*A/*A (p = 0.009, univariate; p = 0.01, multivariate). Acute hepatic graft‐vs.‐host disease developed in 6 (13%) of 46 patients with the GSTA1*A/*A diplotype and in 4 (27%) of 15 patients without this diplotype (p = 0.09, univariate; p = 0.12, multivariate). Ten patients (16%) developed hepatic veno‐occlusive disease. No significant difference was found in the incidence of hepatic veno‐occlusive disease between patients with and without the GSTA1*A/*A diplotype (19.6% vs. 6.7%; p = 0.24). We conclude that the GSTA1*A/*A diplotype is an independent protective factor against acute graft‐vs.‐host disease, especially for skin graft‐vs.‐host disease, and probably for hepatic graft‐vs.‐host disease, in patients using busulfan/cyclophosphamide conditioning. The identification of glutathione S ‐transferase A1 genotypes prior to allogeneic stem cell transplantation could allow conditioning regimens and graft‐vs.‐host disease prophylaxis to be modified to improve outcome.