A transplantable
granulocytic leukemia (GL-13-BC) in strain 13 guinea pigs, which has many similarities to human CML, was used to test the
antineoplastic effects of two
alkylating agents,
busulfan and
cyclophosphamide, administered in the late and early stages of the disease.
Busulfan had a pronounced cytoreductive effect on circulating leukemic cells in the late, pre-
blast crisis stage of this disease but all treated animals, succumbed to the
leukemia with only a marginal increase in survival time relative to that of untreated controls. In this respect the guinea pig model resembles human CML. Survival time was moderately increased with early
busulfan treatment but, as in the late treatment group, all animals succumbed to the
leukemia. A pronounced cytoreductive action on leukemic cells was also observed in guinea pigs treated with
cyclophosphamide. Late treatment with this
drug produced highly variable effects on the survival time of leukemic guinea pigs; of the nine animals treated, no effect was observe in five, three showed a significant increase in survival time and one animal was still in remission without treatment when the experiment was concluded. Early treatment with
cyclophosphamide produced the most striking finding of this study. Two treatments with this
drug produced a complete remission in all of the treated guinea pigs. This remission lasted without further treatment for the duration of the study (greater than 200 days) while all untreated controls died within 27-37 days after receiving leukemic cell transplants. The relevance of these findings to the treatment of human CML is discussed.