Continuous naloxone infusion in two neonates with septic shock.
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Female↗
Biomedical subjects
W L Furman
Publications and source records attributed to W L Furman.
A phase II trial of high-dose methotrexate in previously untreated children and adolescents with high-risk unresectable or metastatic rhabdomyosarcoma.
PURPOSE: The outcome for children with advanced-stage rhabdomyosarcoma remains poor with contemporary treatment regimens. Evaluation of new drugs is important to improve clinical outcome. Because methotrexate has shown promising activity in the treatment of patients with recurrent rhabdomyosarcoma, we conducted a phase II trial in untreated children with advanced-stage disease to evaluate the efficacy and safety of this agent. PATIENTS AND METHODS: Fifteen patients received 1 to 4 courses of high-dose methotrexate (HDMTX, 12 g/m2). Patients then received standard multiagent chemotherapy (vincristine, dactinomycin, cyclophosphamide, ifosfamide, mesna) with cytokine support and local radiotherapy. Patients who responded to HDMTX received four additional courses of this drug during continuation therapy. RESULTS: Twelve patients were evaluable for response after 2 or more courses of HDMTX; 4 achieved a partial response (33.3%). After administration of standard chemotherapy and radiation, the estimated 2-year progression-free survival for all patients was 56% (SD 15%). The drug was well-tolerated and the most common side effects included mucositis, transient elevation of transaminases, and neutropenia. The four patients who received additional courses of HDMTX during continuation therapy had limited toxicity which included mucositis, anemia, and thrombocytopenia. CONCLUSIONS: About one-third of children with previously untreated advanced-stage rhabdomyosarcoma responded to HDMTX. Its different mechanism of action and non-overlapping toxicity with other agents make HDMTX an attractive candidate for incorporation into front-line treatment regimens for rhabdomyosarcoma.
Adolescent↗
Thrombopoietin level in young patients is related to megakaryocyte frequency and platelet count.
PURPOSE: To examine the relationships among platelet counts, bone marrow megakaryocyte frequency, and circulating thrombopoietin (TPO) levels. PATIENTS AND METHODS: TPO levels in 17 children and one young adult with chronic or recurrent thrombocytopenia were measured by ELISA and megakaryocyte frequency was analyzed by light microscopy. Three groups of patients were studied: Group I patients had aplastic anemia and absent or decreased megakaryocytes; Group II patients had intermittent periods of chemotherapy-induced thrombocytopenia; and Group III patients had normal or increased megakaryocytes. Controls consisted of 77 healthy adults. RESULTS: Patients in Group I had markedly increased TPO levels compared to normal controls. Their levels were significantly different (p = 0.03) from those of patients in Group III. The latter had normal or only mildly increased TPO levels except for one patient with myelodysplastic syndrome. Patients in Group II had markedly elevated TPO levels. After their bone marrow and platelet counts recovered from chemotherapy, their TPO levels decreased. In all three groups, a transient increase in platelet count (e.g., after platelet transfusion or anti-D immune globulin therapy) was associated with a moderate decrease in TPO. CONCLUSIONS: From this study, three conclusions can be made: 1) TPO levels are inversely related to megakaryocyte frequency; 2) platelet counts have a modest influence on TPO level; and 3) TPO levels may have clinical utility in diagnosis and management and further our understanding of the pathobiology of the disorders that cause thrombocytopenia.
Adolescent↗
Comparison of cytokines in children with recurrent solid tumors treated with intensive chemotherapy.
PURPOSE: To compare the relative hematopoietic protective effects of recombinant human interleukin-1alpha (rhuIL-1alpha), recombinant human granulocyte macrophage colony-stimulating factor (rhuGM-CSF), and PIXY321, a genetically engineered fusion protein combining interleukin-3 and rhuGM-CSF, in children with refractory solid tumors after treatment with ifosfamide, carboplatin, and etoposide (ICE). PATIENTS AND METHODS: A total of 53 children who had not responded to at least one earlier chemotherapy regimen were enrolled on consecutive trials of ICE chemotherapy alone (n = 14) or with rhuGM-CSF (n = 8), rhuIL-1alpha (n = 10), or PIXY321 (n = 21). The relative hematopoietic effects of these three cytokines were compared retrospectively to each other and to values for patients who received ICE alone. Because one cannot assume that hematopoietic toxicity and response to a given cytokine are independent of the course of chemotherapy, the analysis was restricted to the first treatment course. RESULTS: In this retrospective comparison, 1000 microg/m2/day of rhuGM-CSF reduced the median duration of grade 4 neutropenia (<500/microL) from a median of 17 days (range 3 to 34) in children who received ICE alone to 9 days (range 5 to 11, p = 0.003); it appeared to have a beneficial effect on severe thrombocytopenia (<20,000/microL), reducing the median duration from 4.5 days with ICE alone to 3 days (p = 0.08) and the number of platelet transfusions from a median of 5.75 transfusions (range 0 to 13) to 0 in these two cohorts. No significant improvement in these measures was seen with rhuIL-1alpha or PIXY321. CONCLUSIONS: This analysis suggests that 1000 microg/m2/day of rhuGM-CSF has clinically significant effects on platelet recovery and more effectively ameliorates thrombocytopenia and neutropenia than either rhuIL-1alpha or PIXY321 in the context of ICE chemotherapy. Further dose-intensification will require a combination of cytokines; the optimal dose and combination of these agents awaits further study.
Adolescent↗