TREATMENT OF CANINE GRAFT-VERSUS-HOST DISEASE WITH METHOTREXATE AND CYCLOPHOSPHAMIDE FOLLOWING BONE MARROW TRANSPLANTATION FROM HISTOINCOMPATIBLE DONORS

Abstract

The effectiveness of immunosuppressive therapy with methotrexate was compared to that with cyclophosphamide in preventing or delaying the lethal graft-versus-host disease in dogs following bone marrow transplantation from unrelated donors that were mismatched with their recipients by canine histocompatibility testing. Recipients were prepared for transplantation by 1200 E. of total body irradiation followed by combined infusions of donor marrow and peripheral blood leukocytes. Immunosuppressive drugs were administered on days 1, 3, 6, and 11 posttransplantation and once weekly thereafter until day 102. Four of 6 recipients in group 1 given 0.5 mg methotrexateAg died between days 20 and 33 with acute graft-versus-host disease. One died on day 76 with pneumonia, and one is alive more than 124 days posttransplantation. All 8 recipients in group 2 given 5 mg cyclophosphamide/kg died between 11 and 20 days with graft-versus-host disease. Four of 6 dogs in group 3 treated with 7.5 mg cyclophosphamide/kg died with graft-versus-host disease between days 11 and 13. Two of the. 6 failed to show evidence of marrow repopulation and died on day 13 with pneumonia. Three of 4 dogs in group 4 given 10 mg cyclophosphamide/kg died with marrow aplasia between days 8 and 10. One of the 4 died on day 20 with graft-versus-host disease. Statistical analysis of the survival data demonstrated the superiority of the methotrexate regimen (P