Biomedical subjects

L Helson

Publications and source records attributed to L Helson.

132 records · Page 8Linked to original sources

PubMedDate not supplied

Peripheral blood stem cells in children with solid tumors. Part I. Feasibility and application.

A method for collecting peripheral blood mononuclear cells following mobilizing chemotherapy in pediatric patients is described. The critical elements of the method included temporary heparinization of the patient to reduce citrate overload, and limiting extracorporeal circulation to 15% of the patient's blood volume using packed red blood cells and albumin. A median of 0.9 x 10(8) mononuclear cells/kg per collection were harvested in 40 collections from eight patients with only one episode of fever and chills. Peripheral blood stem cells were reinfused into six of these patients with refractory/recurrent pediatric tumors after intensive chemotherapy. Bone marrow reconstitution followed with a mean of 30 days (19-38) for absolute neutrophils and 48 days (32-275+) for platelets. Previous chemotherapy did not appear to affect peripheral blood stem cell efficacy in reconstituting chemotherapy-ablated bone marrow.

Adolescent↗

PubMedDate not supplied

Peripheral blood stem cells in children with solid tumors. Part II. Immunocytologic detection of tumor cells in bone marrow and peripheral blood stem cell harvests.

Simultaneous comparative assessment of tumor contamination in bone marrow aspirates and peripheral blood stem cell collections using immunocytochemical techniques was done in 6 children with neuroectodermal tumors. In 3 neuroblastoma patients tumor cells were detected in 5 of 16 marrow samples but not in peripheral blood stem cells. Clonogenic tumor cell reinfusion in the autologous support setting may be avoided in neuroblastoma patients by using peripheral blood stem cells.

Adolescent↗

PubMedDate not supplied

Cerebral ventricular fluid distribution of subcutaneous granulocyte-macrophage colony stimulating factor.

After treating a child suffering from disseminated primitive neuroectodermal tumor and hydrocephalus with bilateral ventriculostomies, we administered intravenous high dose thiotepa followed by a single subcutaneous dose of GM-CSF 24 hours later. The appearance and clearance of GM-CSF were measured from both ventricles, one of which was surrounded by tumor. Peak levels of GM-CSF were recorded simultaneously in both ventricles 11 hours after injection. Complete clearance from injection required 15 hours and 31 hours for the tumor-free right ventricle and the tumor-involved left ventricular wall, respectively. Tumor response was ephemeral and limited to ventricular fluid WBC, protein and LDH decreases. Microglia were detected; however, there was no evidence of anti-tumor activity in biopsied tumor tissue. Tumored regions of the brain may have perturbation of GM-CSF distribution and clearance which may contribute to the lack of microglial activity.

Brain Neoplasms↗

PubMedDate not supplied

Hemin toxicity in a human epithelioid sarcoma cell line.

The major cytotoxic component of hemin was identified as metal free protoporphyrin IX in an epithelioid sarcoma cell line (VA-ES-BJ) and a glioblastoma cell line (U-373 MG) by exposing the cell lines to the iron chelator deferoxamine, tin-protoporphyrin IX, and protoporphyrin IX. The contribution of lipid peroxidation and free radical generation to toxicity was examined using DL-buthionine-[S,R]-sulfoximine (BSO), and 21-aminosteroid (lazaroid, U74500A). Hemin caused significantly greater toxicity in VA-ES-BJ than in U-373 MG. While exogenous PpIX was more toxic than hemin in both cell lines, this toxicity was not due to iron depletion following intracellular heme formation since ferric citrate did not reverse PpIX toxicity. Pre-treatment with BSO enhanced hemin toxicity in the VA-ES-BJ cell line but not in U-373 MG, suggesting different modes of toxicity in the two cell lines. Exposure to lazaroid protected only VA-ES-BJ from protoporphyrin-induced toxicity implicating a specific sensitivity to lipid peroxidation and/or free radical generation by this cell line. These characteristics of the VA-ES-BJ cell line distinguish it from the glioblastoma and emphasize its utility for exploring cytotoxic effects of hemin and its precursors.

Buthionine Sulfoximine↗

PubMedDate not supplied

D-CECaT as preoperative chemotherapy for unresectable neuroblastoma in children over one year of age.

The role of intensive pre- and postoperative chemotherapy in unresectable nonmetastatic neuroblastoma is still controversial. A preoperative regimen that included deferoxamine, cyclophosphamide, etoposide, carboplatin and thiotepa (D-CECaT) was evaluated in 10 children over one year of age at diagnosis, and this was followed by surgery and postoperative chemotherapy. After four courses of D-CECaT, the response rate was 9/10 with 3 complete responses, 6 partial responses and 1 minor response. Severe but transitory myelosuppression was the major toxic effect. Complete remission by combined D-CECaT chemotherapy and surgery was obtained in 9/10 patients, while 1 case achieved complete remission only with postoperative chemotherapy. All children are disease-free with a median follow-up of 30.5 months (range: 1+ to 50+). This intensive treatment was effective in both standard- and high-risk unresectable NB. However, whether a less intensive approach and fewer courses can also give similar results in standard-risk cases warrants further study.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Shortened time to recovery from chemotherapy induced neutropenia in pediatric patients with high dose combined cytokines.

Granulocyte colony stimulating factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) are cytokines which have been extensively administered as monotherapy to patients with a variety of hematopoietic disorders at dosages of 5 mcg/kg/day. Because their spectrum of activity is both singular and simultaneously overlapping, we postulated that combined therapy would be more advantageous than monotherapy. Since 1992 we have carried out a study of G-CSF and GM-CSF as monotherapy or in combination in pediatric patients with solid tumors following chemotherapy induced nadirs of 0-800 WBC/mm3. When combined, the cytokines were given twice per day at 2.5 or 5.0 mcg/kg. For the monotherapy groups, either cytokine at 5 mcg/kg or 10 mcg/kg was given once daily. The mean time to recovery from neutropenia nadir ranged from 6.6-8.2 days in patients receiving a total of 10 mcg/kg/day compared to 10.4-10.6 days in patients treated with 5 mcg/kg/day. Side effects were ephemeral eosinophilia. The dosage of 10 mcg/kg/day appears to be a better dosage for pediatric patients with a slight advantage in the combined twice a day schedule (6.6 days).

Adolescent↗