Busulphan aplasia in rabbits: a model for human aplastic anaemia.

Bone marrow histology plays a crucial role in the clinical diagnosis of aplastic anaemia. The nature of the disease means that few studies are available on the histological changes which occur in the early stages of the development of aplasia. We describe here an animal model which may have some relevance in this respect. Rabbits were chronically exposed to busulphan (BU) to induce aplasia. Sequential histological monitoring of the bone marrow was performed to obtain information about the events preceding full-blown aplasia. There was an early decrease and ultimate disappearance of granulo- and megakaryopoiesis with relative sparing of erythropoiesis which showed severe displasia. Increasing lymphoplasmacytoid infiltrate resembling that seen in human aplasia could be observed in the majority of the animals, together with a decrease of the peripheral lymphocyte number. Lymph nodes and spleen did not show lymphocyte depletion and serum gamma-globulin remained stable. Fibrosis was observed in 50% which is in contrast with human aplasia at diagnosis. In half of the animals there was a rise in MCV, which was not correlated with reticulocytosis or degree of dyserythropoiesis. BU-induced aplasia in rabbits, which resembles long-standing grade II human aplasia in many respects, might be a suitable model for the study of aplastic anaemia due to stem cell defects.