Residual marrow injury following cytotoxic drugs

A number of cytotoxic drugs were tested in mice for their ability to produce residual damage to the bone marrow. This was assessed by the ability of the drug to produce depletion of pluripotential stem cells and granulocytic progenitor cells persisting for at least two months after cessation of the drug. Evidence of residual damage was found after administration of mitomycin, chlorambucil and melphalan but not after nitrogen mustard, dimethyl-triazeno-imidazole-carboxamide or adriamycin. Residual damage has previously been found following busulphan and bischloro-nitrosurea and the features in common of the drugs causing residual damage suggest that the effect may require the ability to alkylate pluripotential stem cells. These experimental findings may explain a number of clinical observations in man.