METHOTREXATE REGIMENS FOR CONTROL OF GRAFT-VERSUS-HOST DISEASE IN DOGS WITH ALLOGENEIC MARROW GRAFTS

Abstract

SUMMARY Immunosuppressive therapy with high doses of methotrexate beginning 1 day after allogeneic bone marrow transplantation was evaluated for its effectiveness in preventing or delaying the lethal graftversus-host disease in dogs. A short-term regimen of methotrexate for 6 days after transplantation was compared with a long-term regimen during 102 days postgrafting. Unrelated donor-recipient pairs mismatched by canine histocompatibility testing were used. The recipients were given combined infusions of donor marrow and leukocytes to provide a test system in which the graft-versus-host syndrome is acute and rapidly fatal. Recipients were prepared for transplantation by 1200 R of total body irradiation. Five control dogs, not receiving immunosuppressive therapy, died between 9 and 14 days after transplantation with graft-versus-host disease. Eight of the 9 dogs receiving short-term methotrexate treatment died between 14 and 21 days with graft-versus-host disease, and 1 dog lived 136 days. Seven of the 10 dogs given long-term methotrexate treatment died between 18 and 68 days, and 3 dogs are alive more than 180 days after transplantation. Statistical analysis of the survival data demonstrated the superiority of the long-term methotrexate treatment. The results show that stable long-term chimerism can be achieved in mismatched recipient dogs when intensive methotrexate is begun immediately after marrow transplantation and continued for a prolonged period of time.