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Biomedical subjects

S Meller

Publications and source records attributed to S Meller.

9 recordsLinked to original sources
PubMed1992

Pilot study of high-dose vincristine, etoposide, carboplatin and melphalan with autologous bone marrow rescue in advanced neuroblastoma.

The efficacy and toxicity of a high-dose multiagent consolidation regimen, OMEC (vincristine, melphalan, etoposide and carboplatin), with autologous bone marrow rescue was studied in patients with poor-prognosis neuroblastoma, 20 patients were treated with OMEC, 18 after induction chemotherapy and 2 following relapse. All patients received, per m2, vincristine 4 mg, etoposide 1 g, carboplatin 1.0-1.75 g and melphalan 180 mg followed by bone marrow rescue. 4 patients (20%) died of treatment-related complications. Severe gastrointestinal toxicity occurred in all of these patients, and in 75% of patients overall. 1 of 5 patients with evaluable disease achieved complete remission. 13 patients (65%) have relapsed a median of 10 months (range 3-26) after receiving OMEC. Thus, OMEC was not more effective, yet more toxic, than high-dose melphalan given alone, and the use of similar multiagent regimens with overlapping toxicities in advanced neuroblastoma appears inadvisable.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

'VEEP' in children with Hodgkin's disease--a regimen to decrease late sequelae.

In an attempt to decrease the risk of second malignancies and future infertility in children with Hodgkin's disease (HD) while retaining acceptable remission rates, an anthracycline based regimen containing no alkylating agent has been devised. VEEP contains vincristine, epirubicin, etoposide and prednisolone given at 3 weekly intervals. Forty-four patients, aged 2-15 years, have been treated: ten relapsed patients and 34 previously untreated with chemotherapy (including three relapsed stage I treated initially with radiotherapy). The median follow up for all patients is 25 months (range 6-52 months). The response rate in previously treated patients was 80% (95% CI 44-97%) and five remain alive in remission. The response rate in untreated patients was 88% (95% CI 72-97%) with 62% CR + CR(u) (uncertain/unconfirmed) (95% CI 44-77%). Of four patients who had a final response of CR(u) three have relapsed at 9, 16 and 38 months. Two of the children in CR have relapsed at 6 and 16 months. The relapse free rate at 3 years is 67% (95% CI 17-82%). In this pilot study the event free survival appears somewhat poorer than conventional combinations and further follow up is required to confirm the salvagability of relapsed patients.

Adolescent↗
PubMed1992

Outcome of children with resistant and relapsed Hodgkin's disease.

During the period 1974-89, 169 children with Hodgkin's disease were treated in the Paediatric Oncology Units of the Royal Marsden and St Bartholomew's Hospitals. The overall actuarial survival for the whole group was 81% at 10 years. Thirty-five of the 169 children either did not achieve a complete remission or subsequently relapsed. The estimated actuarial survival from initial relapse or failure of primary treatment was 60% at 5 years and 45% at 10 years. Over half of the patients requiring salvage therapy had declared themselves within 2 years and only 3 relapses occurred more than 3 years from diagnosis. Very few patients remain disease free long term after failure of primary and initial salvage therapy. Patients relapsing within a year of diagnosis or not achieving a complete response to primary therapy and those with disseminated relapse had a poor response to salvage therapy. A significant subgroup of patients had prolonged survival despite multiple relapses. Neither initial histology nor stage affected survival from relapse although numbers in each subgroup were small.

Actuarial Analysis↗
PubMed1992

Phase I/II study of iodine 131 metaiodobenzylguanidine in chemoresistant neuroblastoma: a United Kingdom Children's Cancer Study Group investigation.

PURPOSE: The goal of this study was to evaluate the toxicity of iodine 131 metaiodobenzylguanidine (mIBG) in metastatic neuroblastoma. PATIENTS AND METHODS: A multicenter phase I study of 131I mIBG has been undertaken by the United Kingdom Children's Cancer Study Group (UKCCSG) in children with advanced chemoresistant neuroblastoma. Activity prescription was based on a prescribed whole-body radiation dose, which was established for individual patients by performing an initial tracer investigation with 75 MBq of 131I mIBG. An activity was derived from this pharmacokinetic study that would deliver an initial whole-body-absorbed radiation dose of 1 Gy. Subsequent dose escalations were based on observed toxicity. RESULTS: Twenty-five patients, aged 1 to 10 years, were treated with prescribed whole-body dose levels of 1.0 Gy (n = 2), 2.0 Gy (n = 13), and 2.5 Gy (n = 10). This necessitated administration of 2.4 to 12.1 GBq of activity. Hematologic, hepatic, kidney, and adrenal toxicity were observed, with bone marrow suppression being the principal dose-limiting toxicity. Bone marrow toxicity increased with prescribed whole-body-absorbed radiation dose, with 80% of patients developing grade 3 or 4 thrombocytopenia at a prescribed whole-body radiation dose of 2.5 Gy. Objective evidence of tumor response was seen in soft tissue (primary or nodal disease), bone, and bone marrow, with an overall response rate of 33% (partial response, n = 8; static disease, n = 9; progressive disease, n = 7). CONCLUSIONS: This study has established an effective method of activity prescription that predicts subsequent toxicity, with the maximally tolerated dose being sufficient activity to deliver a whole-body-absorbed radiation dose of 2.5 Gy. The objective response rate is comparable to other single agents in chemoresistant neuroblastoma and suggests that 131I mIBG may be a useful method for targeting radiotherapy in metastatic neuroblastoma.

3-Iodobenzylguanidine↗
PubMed1991

A prospective comparison between magnetic resonance imaging, meta-iodobenzylguanidine scintigraphy and marrow histology/cytology in neuroblastoma.

A prospective comparison between magnetic resonance imaging (MRI), 123I meta-iodobenzylguanidine (mIBG) scintigraphy and posterior iliac crest marrow aspiration and trephine biopsy in 30 assessments (19 patients) showed concordance between the three techniques in 16 assessments (53.3%). In 10 (33.3%), MRI and mIBG revealed abnormalities not detected by marrow biopsy. MRI was the only technique to demonstrate marrow abnormality in four assessments (13.3%). In addition, MRI revealed more sites of abnormality in 16 parallel assessments. We conclude that MRI shows promise as a non-invasive means of detecting bone marrow infiltration by neuroblastoma, but that further evaluation of the specificity of MRI in this setting is indicated.

3-Iodobenzylguanidine↗
PubMed1990

Impact of childhood cancer on return to normal schooling.

Most of the research into the psychosocial impact of treatment for cancer in children has concentrated on effects on the family rather than on the children's return to school. Thus parents and teachers were questioned about the problems experienced by 117 children who returned to school after spending time in hospital. The children comprised 51 with cancer and two groups of control children (34 with chronic diseases such as renal disease and cardiac conditions and 32 with orthopaedic conditions such as thoracic scoliosis, club foot, and injuries resulting from trauma). Children in all three groups experienced problems on returning to school, the greatest number and variety occurring in the children treated for cancer and the fewest in the children with orthopaedic conditions. The variety of physical problems was greatest and the variety of academic problems was least, with psychological and behavioural problems intermediate. Several problems seemed to be related to drug treatment. Several children missed a considerable amount of full time education. Many teachers were unsure of the academic expectations and physical capabilities of children returning to school. To facilitate a smooth return to school for a child with cancer improved liaison is needed between the hospital, school, and home during the child's absence and teachers need to be better informed.

Adolescent↗
PubMed1978

A correlative microscopical analysis of differentiating ovarian follicles of mammals.

The mammalian ovary has been studied by optical microscopy and by scanning and transmission electron microscopy with the purpose of presenting an integrated view of the differentiating mammalian follicle. During follicular development, changes in the granulosa cells are particularly noteworthy and include dramatic modifications in cell shape coincident with antrum formation. The cytoplasmic processes of those granulosa cells immediately surrounding the oocyte, as well as the more peripheral granulosa cells comprising a second and third layer, traverse the zona pellucida, infrequently interdigitate with the microvilli of the egg, and make both desmosomal and gap junction contacts with the oocyte. The zona pellucida is thus distinguished by numerous fenestrations of varying diameters. The membrana limitans (basal lamina) is a bipartite structure composed of (a) a homogenous stratum upon which the peripheral layer of granulosa cells rests, and (b) an outer region of collagen-like fibers. The specific advantages and limitations of the different methodologies utilized to study folliculo-genesis are discussed.

Animals↗
PubMedDate not supplied

[131I]metaiodobenzylguanidine and high-dose chemotherapy with bone marrow rescue in advanced neuroblastoma.

High-dose chemotherapy (HDT) and autologous bone marrow rescue (ABMR) is routinely used as consolidation treatment in advanced neuroblastoma. This study is presently examining the efficacy and toxicity of combined [131I]metaiodobenzylguanidine (131I-MIBG) therapy with HDT and ABMR. Five children (4 male, 1 female), median age of 8 years (range 4-11 years) were treated, 3 at relapse and 2 after initial chemotherapy. A single infusion of 131I-MIBG (median activity 11.1 GBq, range 7.4-11.2 GBq) was followed by HDT and ABMR 14-32 days later. High-dose chemotherapy consisted of carboplatin and melphalan in 4 patients, and vincristine, etoposide, carboplatin and melphalan in 1. One patient developed a septicaemia and died, and another failed to engraft; both had extensive bone marrow infiltration at the time of 131I-MIBG therapy. The combined therapy was well tolerated by the three other patients. Two children have relapsed and died (including one who failed to engraft), and 2 are alive 17 and 41 months after ABMR. In the absence of extensive bone marrow metastases, combined therapy offers potential as a means of consolidating treatment in advanced neuroblastoma.

3-Iodobenzylguanidine↗