title: Muromonab-CD3 (Orthoclone OKT3), methylprednisolone and cyclosporine for acute graft-versus-host disease prophylaxis in allogeneic bone marrow transplantation.
abstract: We report the results of a prospective non-randomized phase II study of Muromonab-CD3 (Orthoclone OKT3), an anti-CD3 monoclonal antibody, with methylprednisolone (MP) and cyclosporine (CSA) for acute GVHD (aGVHD) prophylaxis in 22 hematologic malignancy patients. OKT3 was given at 0.1 mg/kg/day with a maximum dose of 5 mg/day. Initial MP dose was 1000 mg before OKT3, with subsequent doses at 1 mg/kg/day before each OKT3 infusion with a planned taper beginning at day +28. CSA (3 mg/kg/day) was given as a continuous infusion at day -1 and adjusted to maintain serum levels between 250 and 399 ng/ml. Allogeneic BMT donors were HLA-matched siblings (n = 17), single HLA-mismatched-related (n = 1) and HLA-matched unrelated (n = 4). All patients achieved neutrophil engraftment at a median 11 days (range, 8-25 days). By intent-to-treat, the cumulative incidence of grade II-IV aGVHD was 33% (95% CI 13-53%) at a median 26 days post-BMT (range, 14-84 days). Chronic GVHD developed in 11/12 evaluable patients. Eight patients (36%) developed OKT3 first dose reactions; no cases of post-transplant lymphoproliferative disorder were observed. OKT3 depleted peripheral CD3+ cells in vivo as measured by flow cytometry. OKT3+MP+CSA combination is moderately effective aGVHD prophylaxis, however, it is unlikely to be superior to CSA+MTX.
authors.affiliation: Department of Medical Oncology, Gazi University Medical School, Ankara, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Benekli
authors.forename: T
authors.initials: T
authors.lastname: Hahn
authors.forename: B T
authors.initials: BT
authors.lastname: Williams
authors.forename: M
authors.initials: M
authors.lastname: Cooper
authors.forename: H N
authors.initials: HN
authors.lastname: Roy
authors.forename: P
authors.initials: P
authors.lastname: Wallace
authors.forename: C
authors.initials: C
authors.lastname: Stewart
authors.forename: B
authors.initials: B
authors.lastname: Bambach
authors.forename: P L
authors.initials: PL
authors.lastname: McCarthy
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D017252:CD3 Complex; D002648:Child; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000628:therapy*; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000009:adverse effects / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000166:cytology; D014184:Transplantation, Homologous
chemical_list: D017252:CD3 Complex; D016853:Muromonab-CD3; D016572:Cyclosporine; D008775:Methylprednisolone