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

Fifty patients with confirmed local multiple lesions of bone marrow were selected by 99mTc scintigraphy, magnetic resonance imaging and morphologically-supported trepan biopsy from 155 cases of Hodgkin's disease stage II-IVAB. Bone marrow lesions were relatively more common in younger patients 1-11 months after primary tumor detection (an average of 6.5 months). They were detected within 12-156 months (an average of 48 months) among relapsing patients with nodal sclerosis and mixed-cell tumors stage III-IVAB, mostly concomitant with anemia and lymphopenia. Standard combination chemotherapeutical regimens for primary patients (MOPP, ABVD and LOPP) and relapsing ones (CCNU-OPP and ABVD) were effective in those with bone marrow lesions. Side-effects (myelodepression) did not exceed normal levels, provided human recombinant interleukin-1 beta (beta-leukin) was administered for protection and leukopoietic stimulation.
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PMID:[Clinical course and treatment of Hodgkin's disease with concomitant bone marrow lesions]. 1210 62

There is no standard therapy for recurrent anaplastic astrocytoma (AA). Assess response and toxicity of lomustine (CCNU) in recurrent AA following prior surgery, radiotherapy and TMZ in a retrospective case series. Thirty-five adults (18 males; 17 females: median age 42.5 years) with TMZ refractory recurrent AA were treated with lomustine. Seven patients were treated at 1st recurrence and 28 patients were treated at 2nd recurrence. Prior salvage therapy included re-resection in 19, TMZ in 20 and radiotherapy in 7. A cycle of lomustine was defined as 110 mg/m(2) on day 1 only administered once every 6-8 weeks. Success of treatment was defined as progression free survival at 6 months of 40 % or better. Grade 3 or 4 toxicities included anemia (14 patients), constipation (1), fatigue (4), lymphopenia (5), nausea/vomiting (2), neutropenia (8) and thrombocytopenia (10). No grade five toxicities were seen. The median number of cycles of therapy was 3 (range 1-6). Best radiographic response was progressive disease in 14 (40 %), stable disease in 19 (54 %) and partial response in 2 (5.7 %). Median progression free survival (PFS) was 4.5 months (range 1.5-12 months), 6-month PFS was 40 % and 12 month PFS was 11.4 %. Median survival after onset of CCNU was 9.5 months (range 2.5-15 months). Median overall survival was 2.7 years (range 1.7-4.3). In this small retrospective series of patients with recurrent AA refractory to TMZ, lomustine appears to have modest single agent with manageable toxicity. Confirmation in a larger series of similar patients is required.
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PMID:Salvage therapy with lomustine for temozolomide refractory recurrent anaplastic astrocytoma: a retrospective study. 2556 16