Engraftment of DLA-nonidentical bone marrow facilitated by recipient treatment with anti-class II monoclonal antibody and methotrexate.

Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were prepared for transplantation by 9.2 Gy single-dose total-body irradiation (TBI) administered at 7 cGy/min. All recipient dogs received marrow, 4 X 10(8) cells/kg, and no buffy coat cells. In addition to TBI, 19 dogs were given anti-class II monoclonal antibody (mAb) 7.2, either alone or combined with a second anti-class II mAb, HB10a, at doses of 0.2 or 0.4 mg/kg/day on days -5 to 0 or -1 to +3. Seven had hemopoietic engraftment. Ten dogs were given, in addition to TBI, methotrexate (MTX), 0.4 mg/kg/day on days 1, 3, 6, and 11 after grafting, and six had engraftment. Ten dogs were given a combination of mAb 7.2 pregrafting and MTX after grafting, and 9 had evidence of engraftment. Among 7 dogs treated with the irrelevant mAb 31E6.4, only one had engraftment. Thus the administration of anti-class II mAb pregrafting and MTX postgrafting had a beneficial effect in overcoming resistance to histoincompatible marrow grafts. Possibly this effect is more pronounced when both approaches are combined.