Toxicity of very high dose nitrosourea administration

We report a case of inadvertent administration of over twice the usual dose of methyl-CCNU. The patient exhibited an early onset of bone marrow suppression. Profound pancytopenia, including lymphopenia, persisted for over seven weeks, Although early recovery started at about five weeks. Permanent marrow damage was indicated by persistent thrombocytopenia and abnormal megakaryocyte morphology at autopsy, some six months after the single exposure to methyl-CCNU. There was no discernible toxicity to lung, liver, or kidneys. The case suggests that the cummulative bone marrow toxicity seen with nitrosoureas is not dose-schedule sensitive. There is also evidence suggesting that high dose nitrosourea therapy affects a bone marrow target population other than the early stem cell target affected by usual doses of these drugs.