Improved survival in steroid-refractory acute graft versus host disease after non-myeloablative allogeneic transplantation using a daclizumab-based strategy with comprehensive infection prophylaxis.
Approximately 15% of patients undergoing non-myeloablative allogeneic haematopoietical cell transplantation (NMHCT) develop steroid-refractory acute-graft versus host disease (aGVHD), a usually fatal complication. We encountered 18 cases of steroid-refractory aGVHD in 146 patients, undergoing NMHCT from a related human leucocyte antigen-compatible donor following cyclophosphamide/fludarabine-based conditioning. Our initial cohort of steroid-refractory aGVHD patients treated with antithymocyte globulin (ATG) and mycophenolate mofetil (regimen-1: n = 6) had high GVHD-related mortality. Therefore, we investigated an alternative strategy for subsequent patients developing this complication (regimen-2: n = 12), consisting of daclizumab (alone or combined with infliximab/ATG) and targeted broad spectrum antibacterial and aspergillus prophylaxis in conjunction with rapid tapering of steroids to minimize opportunistic infections. In a retrospective analysis, patients receiving regimen-2 were significantly more likely to have complete resolution of GVHD compared with those receiving regimen-1 [12/12 (100%) vs. 1/6 (17%); P < 0.001]. When compared with those receiving regimen-1, regimen-2 patients also had a higher probability of survival at day 100 (100% vs. 50%) and day 200 (73% vs. 17%) post-transplant, and improved overall survival (median 453 d vs. 42 d from aGVHD onset; P < 0.0001). GVHD-related mortality was 89% for regimen-1 patients vs. 17% for regimen-2 patients (P < 0.0001). These data suggest that a co-ordinated approach using immunoregulatory monoclonal antibodies, pre-emptive antimicrobial therapy and judicious steroid withdrawal can dramatically improve outcome in steroid-refractory aGVHD.
Srinivasan
R
R
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1652, USA.
Chakrabarti
S
S
Walsh
T
T
Igarashi
T
T
Takahashi
Y
Y
Kleiner
D
D
Donohue
T
T
Shalabi
R
R
Carvallo
C
C
Barrett
A J
AJ
Geller
N
N
Childs
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D019072:Antibiotic Prophylaxis; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000077561:Daclizumab; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy; D009894:Opportunistic Infections / Q000517:prevention & control; D013256:Steroids / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D013256:Steroids; D000069285:Infliximab; D000077561:Daclizumab