Mismatch on glutathione S-transferase T1 increases the risk of graft-versus-host disease and mortality after allogeneic stem cell transplantation.
Several drug-metabolizing enzymes, preferentially expressed in the liver, have the potential to act as minor histocompatibility antigens. In the present study, we analyzed the impact of glutathione S-transferase T1 (GSTT1), glutathione S-transferase M1, glutathione S-transferase P1, and UDP glucuronosyl transferase 2B17 (UGT2B17) disparities on the outcome of 125 patients undergoing allogeneic hematopoietic stem cell transplantation. Grades 2 to 4 acute graft-versus-host disease (aGVHD) developed in 56.2% versus 73.3% of GSTT1-matched versus mismatched patients (P = .048). Remarkably, 8.6% GSTT1-matched patients developed grades 2 to 4 liver aGVHD, compared with 36.8% among GSTT1-mismatched recipients (P < .001). Regarding chronic graft-versus-host disease (cGVHD), 34.8% versus 70.7% matched versus mismatched patients developed overall cGVHD (P = .038) and 16.3% versus 48% developed hepatic cGVHD (P = .006). We also found a strong association between the UGT2B17 mismatch and the risk of severe aGVHD (P = .001), especially with gut involvement (P < .001). Most striking was the influence of the GSTT1 mismatch on nonrelapse mortality (26.8% versus 52.6%, P = .031) and overall survival (62% versus 36.9%, P = .045). In summary, UGT2B17 and GSTT1 mismatch are risk factors for the development of GVHD and the latter also influences on mortality and survival after allogeneic transplantation from HLA-identical donors.
Department of Immunology, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
María José
MJ
Martínez-Bravo
Department of Haematology, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
Cristina
C
Calderón-Cabrera
Department of Haematology, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
Francisco José
FJ
Márquez-Malaver
Department of Haematology, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
Nancy
N
Rodríguez
Department of Immunology, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
Marta
M
Guijarro
Department of Haematology, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
Idelfonso
I
Espigado
Department of Immunology, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
Antonio
A
Núñez-Roldán
Department of Haematology, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Seville, Spain. Electronic address: josea.perez.simon.sspa@juntadeandalucia.es.
José Antonio
JA
Pérez-Simón
Department of Immunology, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Seville, Spain. Electronic address: iaguilera-ibis@us.es.
Isabel
I
Aguilera
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D005982:Glutathione Transferase / Q000009:adverse effects*; D006086:Graft vs Host Disease / Q000209:etiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D012306:Risk; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014184:Transplantation, Homologous / Q000009:adverse effects* / Q000379:methods; D055815:Young Adult
C413545:glutathione S-transferase T1; D005982:Glutathione Transferase
Allogeneic hematopoietic stem cell transplantation (allo-HSCT); Donor-recipient mismatch; Glutathione S-transferase T1; Graft-versus host disease (GHVD); Minor histocompatibility antigens; UDP-glucuronosyl transferase 2B17