Pre-emptive therapy of acute graft-versus-host disease: a pilot study with antithymocyte globulin (ATG).
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.
Bacigalupo
A
A
Divisione Ematologia II, Ospedale San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
Oneto
R
R
Lamparelli
T
T
Gualandi
F
F
Bregante
S
S
Raiola
A M
AM
Di Grazia
C
C
Dominietto
A
A
Romagnani
C
C
Bruno
B
B
Van Lint
M T
MT
Frassoni
F
F
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
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents