Premium
Improved survival in steroid‐refractory acute graft versus host disease after non‐myeloablative allogeneic transplantation using a daclizumab‐based strategy with comprehensive infection prophylaxis
Author(s) -
Srinivasan R.,
Chakrabarti S.,
Walsh T.,
Igarashi T.,
Takahashi Y.,
Kleiner D.,
Donohue T.,
Shalabi R.,
Carvallo C.,
Barrett A. J.,
Geller N.,
Childs R.
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2004.04856.x
Subject(s) - medicine , daclizumab , regimen , fludarabine , transplantation , gastroenterology , cyclophosphamide , surgery , graft versus host disease , busulfan , hematopoietic stem cell transplantation , chemotherapy , tacrolimus
Summary 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.