title: Methotrexate Reduces the Incidence of Severe Acute Graft-versus-Host Disease without Increasing the Risk of Relapse after Reduced-Intensity Allogeneic Stem Cell Transplantation from Unrelated Donors.
abstract: Optimized prophylaxis against graft-versus-host disease (GVHD) after unrelated reduced-intensity allogeneic transplantation when preceded by a conditioning regimen utilizing antithymocyte globulin (ATG) is poorly defined. To investigate the effects of methotrexate (MTX) in this treatment setting, we conducted a retrospective analysis. Sixty-three patients were selected based on the administration of a total dose of 5 mg/kg of ATG in the conditioning regimen and then separated into either group M+ (n = 39), which received MTX or group M- (n = 24), which did not. All patients received cyclosporine. In the M- and M+ groups, cumulative incidences (CI) of grade III-IV acute GVHD (aGVHD) were 43% and 10%, respectively (P = .002). Multivariate analysis indicated that grade III-IV aGVHD was favored by both the absence of MTX and the provision of a female donor for a male recipient. At 2 years, the M+ and M- groups exhibited, respectively: overall survival of 69% and 40% (P = .06), disease-free survival of 57% and 43% (P = .2), nonrelapse mortality of 20% and 44% (P = .1), and incidence of relapse of 27% and 35% (P = .6). These data suggest that MTX reduces the incidence of severe aGVHD without increasing the risk of relapse but with an accompanying trend toward improved survival after unrelated reduced-intensity transplantation with ATG in the conditioning regimen.
authors.affiliation: Service des Maladies du Sang, CHU Haut-Lévêque, Bordeaux, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Vigouroux
authors.forename: Reza
authors.initials: R
authors.lastname: Tabrizi
authors.forename: Cyril
authors.initials: C
authors.lastname: Melot
authors.forename: Joelle
authors.initials: J
authors.lastname: Coiffard
authors.forename: Xavier
authors.initials: X
authors.lastname: Lafarge
authors.forename: Gérald
authors.initials: G
authors.lastname: Marit
authors.forename: Krimo
authors.initials: K
authors.lastname: Bouabdallah
authors.forename: Arnaud
authors.initials: A
authors.lastname: Pigneux
authors.forename: Thibaut
authors.initials: T
authors.lastname: Leguay
authors.forename: Marie-Sarah
authors.initials: MS
authors.lastname: Dilhuydy
authors.forename: Anna
authors.initials: A
authors.lastname: Schmitt
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Boiron
authors.forename: Noël
authors.initials: N
authors.lastname: Milpied
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents; D015994:Incidence; D008297:Male; D008727:Methotrexate / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies; D055502:Secondary Prevention; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D000964:Antimetabolites, Antineoplastic; D007166:Immunosuppressive Agents; D008727:Methotrexate