COMBINATION GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS USING IMMUNOTOXIN (ANTI-CD5-RTA [XOMAZYME-CD5]) PLUS METHOTREXATE AND CYCLOSPORINE OR PREDNISONE AFTER UNRELATED DONOR MARROW TRANSPLANTATION

Unrelated donor (URD) bone marrow transplantation (BMT) is associated with more frequent and more therapy-resistant graft-versus-host diseas e (GVHD). We tested an in vivo immunotoxin with direct cytolytic poten cy against CD5-expressing T lymphocytes (Xomazyme-CD5) for GVHD prophy laxis after URD BMT. The immunotoxin was given in vivo (0.1 mg/kg/day) for 3 weeks following transplantation in combination with methotrexat e + prednisone (MXP; n = 16) or methotrexate + cyclosporine (MCX; n = 6). The 22 patients (10 phenotypically matched with their donors and 1 2 partially matched) received unmanipulated marrow. MXP was well toler ated, while MCX led to unacceptable nephrotoxicity, weight gain and ed ema. Four patients died of early complications. Thirteen of 17 evaluab le patients achieved myeloid engraftment by 17-40 days (median 24 days ). Acute GVHD developed in 9 of 15 evaluable patients (5 grade III/IV) . Six of 8 evaluable patients developed chronic GVHD. Four patients su rvive 1.1-2 years after BMT. Although this immunotoxin has previously shown potency in prophylaxis of murine GVHD and therapy of human GVHD, in this trial inadequate immunosuppressive potency of the immunotoxin combinations was associated with unacceptable clinical toxicity. Aggr essive immunoprophylaxis against GVHD is required to improve the succe ss of URD BMT.