Comparative Effects of Cytotoxic Agents on Transplanted Hematopoietic and Antibody-Producing Cells2

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Abstract
The effects of 6 cytotoxic agents were studied on recently transplanted hematopoietic colony-forming units and adoptively transferred antibody-forming cells. Methotrexate, 6-mercaptopurine, and actinomycin D were most effective against both cell lines when given 3 days or longer after cell transplant, which suggests that these compounds profoundly affect actively proliferating cells. Cyclophosphamide exerted a time-dependent effect on antibody production similar to that of methotrexate, but its effect on the colony-forming units was not time related, which suggests that all phases of the hematopoietic cells' proliferative cycle are affected equally. 1,3-Bis(2-chloroethyl)-1-nitrosourea affected both cell lines most markedly when given shortly after marrow transplantation indicating that resting or lag phase cells are most sensitive. Of all agents studied, antilymphocyte serum suppressed antibody production most and affected hematopoietic cells least, especially when given in high doses at the time of or shortly after cell transplantation. Cyclophosphamide and methotrexate achieved more antibody suppression with less hematopoietic cell suppression than the other cytotoxic drugs studied. From these studies one might predict that these latter 3 agents are useful in the treatment of graft-versus-host reactions.

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