An Animal Model of Chronic Aplastic Marrow Failure. I. Late Marrow Failure After Busulfan

An animal model of chronic aplastic marrow failure was produced by administering busulfan to mice in high dosage for a prolonged period. Mice which survived 60 or more days following cessation of the drug appeared well: in 59% the blood was normal, and in 35% the marrow cellularity was within the normal range; those mice with evident abnormality in the blood and marrow showed only minimal cytopenia in the peripheral blood and moderate decreases in marrow cellularity. Nevertheless, by 240 days 80% of the mice had become ill and died. Sacrifice prior to death showed that aplasia of the marrow and cytopenia (most often pancytopenia) were present in the majority of mice. These syndromes of persistent mild marrow hypoplasia and late severe marrow failure which followed busulfan may be suitable experimental models for studying the late effects of myelotoxic agents and the syndrome of chronic aplastic marrow failure in man.