Cytogenetic and Morphologic Abnormalities in Human Bone Marrow Cells during Cytosine Arabinoside Therapy

The cytogenetic and morphologic abnormalities arising in the bone marrow following therapy with 1-β-D-arabinofuranosylcytosine hydrochloride (cytosine arabinoside) were studied with 10 patients with various neoplasms. A 5-day course of daily, rapid administration of the drug was employed at a dose of 150-200 mg./m₂ body surface area. Within 24 hours there was a high incidence of chromosomal aberrations in both granulocytic and erythroid marrow cells. These aberrations consisted of chromatid breaks, erosions, despiralization, precocious separation of the chromatids at the centromeric region, and extensive fragmentation. Prominent morphologic abnormalities were seen in nondividing cells of the erythroid series, but were absent from the granulocytic precursors. Following cessation of cytosine arabinoside therapy, the morphologic and cytogenetic abnormalities rapidly returned to normal. These features were discussed in relation to the known pharmacology of cytosine arabinoside.