Cytologic Dysplasia Occurring After Busulfan (Myleran⌖) Therapy

Abstract

A patient is presented with chronic granulocytic leukemia who received continuous, prolonged busulfan therapy and developed 3 complications of therapy: widespread cytologic dysplasia, a syndrome resembling adrenocortical insufficiency, and atrophic bronchitis. A specific endocrine defect could not be demonstrated. Nuclear abnormalities were found in megakaryocytes of the bone marrow and in respiratory and cervical epithelial cells in cytology preparations. There abnormalities consisted of nuclear enlargement, density of nuclear staining suggesting increase of chromatin mass, distortion and angularity of nuclear outline, and the presence of macronucleoli. The differentiation from malignant cells was difficult, and only the history of drug administration, knowledge of previous reports of dysplasias due to busulfan and such evidence of cell maturity as the cilia in the abnormal respiratory epithelium prevented misinterpretation of the cells. Although there is evidence that alkylating agents are mutagenic, there is no experimental data to suggest that busulfan is carcinogenic. It would appear that the serious complications of busulfan therapy described in this report only occur in those cases where busulfan has been given over a prolonged period of time. It is suggested that these untoward reactions can be prevented by using busulfan on an intermittent regimen as indicated by the activity of the leukemic process.