Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methyl-CCNU, a compound with marked antitumor activity against the solid Lewis lung tumor in mice, was submitted to a preclinical pharmacologic evaluation. The toxicity of a single iv infusion was tested in 37 beagle dogs and 21 rhesus monkeys. The minimum lethal dose (LD) in dogs was 14 mg/kg and five of six dogs died within 7-10 days after treatment from hematopoietic toxicity with neutropenia, lymphopenia, anemia, and concomitant sepsis. Metaplasia of the intestinal epithelium also occurred. Thrombocytopenia was not observed. Dogs treated with 9.27-1.56 mg/kg exhibited reversible neutropenia and lymphopenia but survived without severe morbidity or histopathologic lesions. In monkeys, interstitial nephritis was the treatment-limiting toxicity and three of six monkeys treated with 45 or 30 mg/kg died, became moribund, or exhibited severe renal histopathologic lesions. One monkey treated with 45 mg/kg had degeneration of the testes. Survivors exhibited reversible toxicity and no histopathologic lesions. Treatment with doses as low as 7.5 mg/kg caused reversible neutropenia, lymphopenia, and anemia. The largest nontoxic dose for a single iv infusion was 3.12 mg/kg (62.40 mg/m2) for the dog and 3.75 mg/kg (45 mg/m2) for the monkey. These and earlier observations showed that methyl-CCNU had approximately one third the toxicity of CCNU. Methyl-CCNU also did not cause the delayed hepatic toxicity which is characteristic of CCNU treatment in the dog.
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PMID:Methyl-CCNU: preclinical toxicologic evaluation of a single iv infusion in dogs and monkeys. 82 19

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.
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PMID:Toxicity of very high dose nitrosourea administration. 711