Intravenous monoclonal antibody (BT 5/9) for the treatment of acute graft-versus-host disease.

Andrea Bacigalupo, Giorgio Corte, Dunia Ramarli, Maria Teresa van Lint, Francesco Frassoni, Alberto Marmont, Dipartimento di Ematologia ed Immunbiologia, Ospedale San Martino, I-16132 Genova (Italy) Acute graft-versus-host disease (GvHD) is a common complication of allogeneic bone marrow transplantation (BMT), despite the use of prophylactic methotrexate or cyclosporin A (CyA) [1]. Severe GvHD (grade III-IV) occurs in 15–20% of allogeneic BM recipients, and is associated with a high (over 50%) mortality rate [1]. Treatment of severe GvHD includes antilympho-cytic globulin [2], high-dose methylprednisolone [3] and, recently, pan-T monoclonal antibodies (Mab) [4,5]. The risk of such treatments is mainly immunosup-pression, which has been associated with the occurrence of non-Hodgkin lymphoma in the case of OKT3Mab[5]. We are now reporting a pilot study designed to test the efficacy of a helper-T Mab (BT 5/9) for the treatment of severe GvHD. BT 5/9 is an IgG3 which does not bind complement; it reacts with 15–20% of peripheral blood T cells in normal individuals and identifies helper cells in assays for in vitro Ig synthesis [6]. In addition, removal of BT 5/9+ cells from a mixed leukocyte reaction prevents both proliferation and generation of cytotoxic T lymphocytes (CTL) from BT 5/9cells [7]. Patients were all recipients of an HLA identical allogeneic BMT. All patients, except UPN 999 who was given methotrexate according to the Seattle protocol [1], received CyA for GvHD prophylaxis, as described elsewhere [8], and were diagnosed as having severe GvHD according to published clinical criteria [1]. They were all treated with BT 5/9, after proving refractory to steroids (UPN 77, 78, 85, 90, 92, 97, 100), or ALG (UPN 999). The latter patient 1 Supported by C.N.R. (P.F.O.) CT 84.00661.44. was grafted in another unit and treated with BT 5/9 in the Department of Hematology of Cagliari. All patients received 2 mg of BT 5/9 per m2 per day on each of 5 consecutive days, after premedication with anti-histamines and steroids (0.5 mg/kg of prednisolone). Relevant clinical data are shown in table I. The proportion of circulating BT 5/9+ T cells dropped from 3–35% on day 0 of treatment to 1– 10% on day 5 (table I). The mean grading of GvHD was 2.7 (range II-III) on day 0 of treatment, 2 on day 14 (range OIII) and 1.4 on day 30 (range O-III) (table I). There were 4 complete responders, 2 partial