title: Pre-emptive therapy of acute graft-versus-host disease: a pilot study with antithymocyte globulin (ATG).
abstract: We have previously shown that patients at high risk of graft-versus-host disease (GVHD) and transplant-related mortality (TRM) can be identified on day +7 following an allogeneic bone marrow transplant (BMT), based on serum bilirubin and blood urea nitrogen levels. One possible approach to reduce the risk of GVHD and TRM, is pre-emptive treatment with T cell antibodies. We report a pilot study testing the feasibility of this approach in 18 high risk patients, with a median age of 41, 83% of whom had advanced disease, undergoing an alternative donor BMT (family mismatched in five and unrelated in 13). The patients received three doses of rabbit antithymocyte globulin (ATG) (Thymoglobuline; Sangstat) 1.25 mg/kg on alternate days, starting at a median interval of 11 days (range 7-13) after BMT. Controls were 20 historical unrelated donor transplants (median age 35, 63% with advanced disease), with a high score from our original publication in 1999. The actuarial 1 year TRM of the ATG-treated patients was 40% compared to 60% for untreated controls (P = 0.06). Severe grade III-IV aGVHD developed in 27% of the ATG-treated patients, and in 55% of the controls (P = 0.08). This study indicates that early pre-emptive treatment of aGVHD in day +7 high risk patients is feasible and may lead to a reduction of aGVHD and TRM. This approach is being tested in a prospective randomized trial.
authors.affiliation: Divisione Ematologia II, Ospedale San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: R
authors.initials: R
authors.lastname: Oneto
authors.forename: T
authors.initials: T
authors.lastname: Lamparelli
authors.forename: F
authors.initials: F
authors.lastname: Gualandi
authors.forename: S
authors.initials: S
authors.lastname: Bregante
authors.forename: A M
authors.initials: AM
authors.lastname: Raiola
authors.forename: C
authors.initials: C
authors.lastname: Di Grazia
authors.forename: A
authors.initials: A
authors.lastname: Dominietto
authors.forename: C
authors.initials: C
authors.lastname: Romagnani
authors.forename: B
authors.initials: B
authors.lastname: Bruno
authors.forename: M T
authors.initials: MT
authors.lastname: Van Lint
authors.forename: F
authors.initials: F
authors.lastname: Frassoni
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000401:mortality; D002423:Cause of Death; D002648:Child; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents