levoleucovorin and Neuroblastoma

Topics: Child; Clinical Trials as Topic; Humans; Infusions, Parenteral; Leucovorin; Methotrexate; Neoplasm Metastasis; Neuroblastoma

Prophylactic antibiotics decrease mortality and morbidity in patients with hematological malignancies following intensive chemotherapy. However, the efficacy of prophylactic antibiotics for pediatric patients with solid tumors remains unclear.. We retrospectively assessed 103 neutropenic periods from 26 patients with neuroblastoma or brain tumors following three different intensity chemotherapy regimens (05A3, A, and B). While piperacillin was intravenously administered as prophylaxis (PIPC prophylaxis group), the historical control group received no prophylaxis. As patients exhibited a variable degree of myelosuppression based on the intensity of the chemotherapy regimen, we separately evaluated the frequency and severity of febrile neutropenia (FN) in each regimen.. Following intensive chemotherapy, we observed a significantly lower frequency of FN in the PIPC prophylaxis group compared with the historical control group in both regimen 05A3 (20% vs 65%; P = 0.01) and regimen A (56% vs 93%; P = 0.02). We also observed a shorter duration of fever, lower maximum fever, and lower C-reactive protein levels in the PIPC prophylaxis group compared with the historical control group after regimens 05A3 and A. Conversely, the frequency and severity of FN were not different between the two groups after moderate-intensity chemotherapy (regimen B). However, a longitudinal routine surveillance study of Pseudomonas aeruginosa also indicated a reduction in the susceptibility to PIPC throughout the study period.. Although PIPC prophylaxis might provide an advantage for severe neutropenia in pediatric patients with solid tumors, there is concern regarding bacterial resistance to antibiotics. Therefore, further careful examination is necessary for adaptation.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carboplatin; Child; Child, Preschool; Drug Resistance, Microbial; Female; Fever; Fluorouracil; Humans; Infant; Leucovorin; Male; Methotrexate; Neuroblastoma; Neutropenia; Piperacillin; Retrospective Studies

The metabolic role of 5-formyltetrahydrofolate is not known; however, it is an inhibitor of several folate-dependent enzymes including serine hydroxymethyltransferase. Methenyltetrahydrofolate synthetase (MTHFS) is the only enzyme known to metabolize 5-formyltetrahydrofolate and catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate. In order to address the function of 5-formyltetrahydrofolate in mammalian cells, intracellular 5-formyltetrahydrofolate levels were depleted in human 5Y neuroblastoma by overexpressing the human cDNA encoding MTHFS (5YMTHFS cells). When cultured with 2 mM exogenous glycine, the intracellular serine and glycine concentrations in 5YMTHFS cells are elevated approximately 3-fold relative to 5Y cells; 5YMTHFS cells do not contain measurable levels of free methionine and display a 30-40% decrease in cell proliferation rates compared with 5Y cells. Medium supplemented with pharmacological levels of exogenous folinate or methionine ameliorated the glycine induced growth inhibition. Analysis of the folate derivatives demonstrated that 5-methyltetrahydrofolate accounts for 30% of total cellular folate in 5Y cells when cultured with 5 mM exogenous glycine. 5YMTHFS cells do not contain detectable levels of 5-methyltetrahydrofolate under the same culture conditions. These results suggest that 5-formyltetrahydrofolate inhibits serine hydroxymethyltransferase activity in vivo and that serine synthesis and homocysteine remethylation compete for one-carbon units in the cytoplasm.

Topics: Antidotes; Gene Expression; Homocysteine; Humans; Leucovorin; Methylation; Methylenetetrahydrofolate Dehydrogenase (NADP); Neuroblastoma; Tumor Cells, Cultured

Topics: Adolescent; Child; Child, Preschool; Drug Administration Schedule; Humans; Infant; Leucovorin; Leukemia; Lymphoma; Methotrexate; Neuroblastoma

Topics: Animals; Cells, Cultured; Chromatography, Paper; Folic Acid Antagonists; Growth; Kinetics; Leucovorin; Methyltransferases; Mice; Neoplasms, Experimental; Neuroblastoma; Quinazolines; Thymidine; Thymidylate Synthase