Cyclophosphamide regimens in rhesus monkey with and without marrow infusion.

Abstract

Summary Hematological and pathological effects of various high-dose regimens of cyclophosphamide (CY) were evaluated in rhesus monkeys. An effort was made to find a dose range at which infusion of autologous marrow would prevent lethality. In addition, allogeneic marrow was transplanted following very large but nonlethal doses of CY. Twenty-five monkeys were given CY in doses of 100 to 240 mg/kg over 1- to 4-day periods. These doses of CY produced severe hemopoietic depression and generalized toxicity. Uneventful hemopoietic recovery and survival was the rule in monkeys given up to 200 mg/kg. After 240 mg/kg, most monkeys died, even when stored autologous marrow was infused, probably because of nonhemopoietic toxic effects of CY. Four groups of recipients (28 monkeys) were given nonlethal doses of CY followed by marrow infusion from donors of opposite sex. Criteria for allogeneic marrow engraftment were rising blood cell counts following the post-CY decline, occurrence of a lethal graft-versus-host disease, and the cytogenetic demonstration of marrow cells with donor karyotype. It was found that consistent allogeneic marrow grafts could be achieved after a nonlethal dose of 180 mg CY/kg administered over a 2-day period. Extending the total dose of CY over a 4-day instead of a 2-day period was less effective in preparing the host for acceptance of the marrow graft. After 150 mg CY/kg given over a 2-day or a 4-day period, permanent engraftment was not observed.