PubMed Health⌕ Search

Biomedical subjects

R Pinkerton

Publications and source records attributed to R Pinkerton.

At least 37 records · Page 2Linked to original sources
PubMed1997

Bilineal acute leukemia of B and T lineage with a novel translocation t(9;17)(p11;q11).

We describe a case of bilineal leukemia in a 5-year old boy with a rare immunophenotype and the novel translocation t(9;17)(p11;q11) as the sole chromosomal abnormality. Two immunologically distinct blast cell subsets expressed T-markers (CD2, CD5, CD7) and common ALL markers (TdT, CD19, CD22, CD10), respectively. Both cell populations were CD34 negative. The patient, who presented with CNS leukemia, responded promptly to standard chemotherapy for lymphoblastic leukemia and remains in complete remission 20 months from diagnosis. Other translocations between chromosomes 9 and 17 have been infrequently reported in a variety of leukemias but as yet their biologic significance is unknown. The clinical course of this case suggests that t(9;17)(p11;q11) may not have an adverse influence on the disease outcome. However, the role of t(9;17) in the pathogenesis of this unusual lymphoid phenotype remains unresolved.

Acute Disease↗
PubMed1996

Gains, losses, and amplification of genomic material in rhabdomyosarcoma analyzed by comparative genomic hybridization.

In this study, 10 embryonal and 14 alveolar rhabdomyosarcoma (RMS) tumor samples, including 4 cell lines derived from tumors of the alveolar subtype, were analyzed by comparative genomic hybridization. In the embryonal tumors, the gain of whole or most of various chromosomes, notably chromosomes 2 (60% of cases), 13 (60%), 12 (60%), 8 (60%), 7 (50%), 17 (40%), 18 (40%), and 19 (40%), and the loss of chromosomes 16 (40%), 10 (30%), 15 (20%), and 14 (20%) were found. One case showed evidence of genomic amplification at 12q13-15. In contrast, the alveolar tumors and cell lines showed consistent evidence of genomic amplification, with multiple amplicons in some cases. The amplicons were localized to l2q13-15 (50%), 2p24 (36%), 13q14 (14%), l3q32 (14%), 1q36 (14%), 1q21 (7%), and 8q13-21 (7%). Four cases had additional copies of chromosome 17 or l7q. These changes were in addition to the presence of fusion gene transcripts that are associated with translocations specific to alveolar RMS. The results show that distinct patterns of primarily gains of specific chromosomal material are associated with the embryonal subtype of RMS, and that genomic amplification seems to play an important role in the alveolar subtype. Notably, these distinct changes predominantly involved chromosomes 2, 12, and 13 in both subtypes.

Adolescent↗
PubMed1996

Child care quality and children's behavioral adjustment: a four-year longitudinal study.

Studies of extensive, full-time child care in infancy and early childhood have shown negative, positive and no effects on children's social-emotional development. The current study explored the prediction of children's behavioral adjustment 4 years after assessments of daycare center quality (e.g. caregiver-child interactions, caregiver-to-child ratios) and of the home and family environment (e.g. parental stress, discipline). Participants included 141 school-age children (73 girls) and their employed mothers (91% Euro-American) who had made use of full-time child care when the children were toddlers or preschoolers. Home environment factors and earlier behaviors were predictive of individual differences in adjustment 4 years later, particularly for maternal ratings of child behaviors. By contrast, indicators of center quality were generally unrelated to mother and teacher ratings of behavioral adjustment.

Caregivers↗
PubMed1996

Autologous stem cell transplantation in solid tumours of childhood.

High-dose chemoradiotherapy (HDCRT) followed by autologous stem cell (ASC) rescue is now widely used in a number of childhood malignancies. The most common to date is neuroblastoma, where it now has an established role as consolidation of initial complete remission in children over the age of 1 year with stage 4 disease. High-dose melphalan alone prolongs progression-free survival, with a small increase in long-term survival. The value of a total body irradiation (TBI)-based regimen is currently under randomized evaluation. In soft-tissue sarcoma, such as rhabdomyosarcoma or Ewing's sarcoma of bone or soft tissue, high-dose therapy has been used to consolidate initial complete or partial remission. The benefit has not been demonstrated in randomized studies but chemotherapy-alone regimens based on combined alkylating agents appear to be of potential value. Other tumours have been treated in this way but the place of high-dose therapy remains entirely unclear. It is possible that inherently chemosensitive tumours, such as Wilm's tumour, may be candidates where standard treatment has failed. The replacement of bone marrow reinfusion with cytokine-primed peripheral blood stem cell (PBSC) rescue has reduced the morbidity of these procedures. The issue of the potential risk of reinfusing tumour cells has been addressed in neuroblastoma where purging using immunodepletion or in vitro chemotherapy has been carried out.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Respiratory symptoms in children dying from malignant disease.

Shortness of breath and other respiratory symptoms frequently complicate the symptomatic management of terminally ill adults. The extent of the problem in children is not known, but anecdotal evidence from nurses and physicians experienced in paediatric oncology has suggested that respiratory problems are less frequent in children dying from malignant disease than in adults. This is a retrospective review of all children dying from cancer under the care of the symptom care team at the Royal Marsden Hospital between 1982 and 1993. The results show that respiratory symptoms were recorded during the last three months of life in 40% of analysable case histories. The nature of respiratory symptoms in paediatric cancer patients is discussed.

Child↗
PubMed1995

Impact of megatherapy in children with high-risk Ewing's tumours in complete remission: a report from the EBMT Solid Tumour Registry.

The European BMT Solid Tumour Registry (EBMT-STR) received reports from 21 European transplant centers on 63 patients (50 Ewing's sarcomas and 13 peripheral neuroectodermal tumours) in first (n = 32) or second CR (n = 31) consolidated with megatherapy and BM and/or PSC rescue between December 1982 and November 1992. There were 31 males and 32 females with a median age of 12 years (range 1-30 years) at megatherapy. The median follow-up time since megatherapy is 4 years (range 1 month to 10 years), Thirty-two patients with metastatic disease at diagnosis (22 had metastases to the bone and/or bone marrow) and consolidated in CR1 reached an actuarial event-free survival (EFS) of 21% at 5 years. Thirty one patients in CR2 achieved an actuarial EFS of 32% at 5 years. Favourable outcome was limited to relapse patients with localised disease at initial diagnosis. Distant relapse had a more favourable prognosis than local failure. Analysis of the different megatherapy strategies could not identify a significantly superior approach, nor is there convincing evidence in favour of double graft procedures. From the above results it appears that consolidation treatment by megatherapy contributes to improved EFS rates in high-risk patients compared with historical experience. Major questions for the future to be addressed prior to randomised studies include agreement on the definition of high-risk patients and the most efficient megatherapy procedure.

Adolescent↗
PubMed1995

[Massive chemotherapy followed by bone marrow graft in pediatric oncology: arguments against].

The outcome of most paediatric malignancies has been improved through dose escalation. Megatherapy followed by bone marrow rescue remains an experimental approach requiring appropriate comparison with the newer forms of chemotherapy. Bone marrow transplantation registries provide only very general information due to the marked heterogeneity of the data based on single arm studies. Randomised studies in poor prognosis tumors and advanced malignancies are still required.

Adolescent↗
PubMed1994

Conducting clinical research in the new NHS: the model of cancer. United Kingdom Coordinating Committee on Cancer Research.

The United Kingdom Coordinating Committee on Cancer Research represents the major organizations funding cancer research in the United Kingdom. The deliberations of a working party convened by the committee to evaluate recently expressed concerns that the changes in the NHS threaten research, especially clinical trials to evaluate new treatments, are reported. A survey of contributors to trials coordinated by the committee showed that half are now experiencing difficulties in continuing to participate in clinical trials. The two major problems identified were lack of time and of staff, especially for NHS staff in non-teaching hospitals. Recent changes in junior doctors' hours and proposed reductions in the length of time for training will exacerbate this. It is possible to identify the direct and indirect excess costs of conducting research in the NHS, but currently the mechanism does not exist to designate funds specifically for this purpose. Consultation with the regional directors of research and development confirmed that the service increment for teaching and research is not the solution for this. Proposals are made to secure future clinical research in the NHS, including finance, indemnity, the licensing of new drugs, the greater use of nurse counsellors, and the value of cancer registries.

Clinical Trials as Topic↗
PubMed1994

Chemoprophylaxis for pulmonary aspergillosis during intensive chemotherapy.

Three children who developed pulmonary aspergillosis while being treated for leukaemia or non-Hodgkin's lymphoma. Each child continued with intensive myelosuppressive chemotherapy regimens during the infection and each was successfully treated with antifungal prophylaxis based on itraconazole by mouth. Amphotericin B was also given during periods of severe neutropenia. No reactivation of the fungal infection was seen.

Amphotericin B↗
PubMed1994

Comparison of auto versus allografting as consolidation of primary treatments in advanced neuroblastoma over one year of age at diagnosis: report from the European Group for Bone Marrow Transplantation.

A case control study was performed to investigate the potential advantage of allogeneic bone marrow transplantation in advanced or poorly responding neuroblastoma first remission patients using the European BMT Solid Tumor Registry. Seventeen allogeneic and 34 autologous bone marrow transplantation (BMT) cases were matched based on a number of prognostic factors including age, sex, prior treatment duration, pre-graft response status and bone and BM involvement before BMT. Only single BMT procedures are included. The median age at diagnosis was 47 months (range 18-113 months). The median follow-up time since BMT is 58 months (range 13-133 months). The only significant prognostic factor within the allogeneic BMT (p = 0.012) and autologous BMT groups (p = 0.025) was residual skeletal disease before BMT, detected by mIBG in 86% of the cases. However, the progression-free survival was not significantly different: 35% and 41% at 2 years, respectively. Only half of the allogeneic BMT patients had developed graft-versus-host disease (GVHD): 7 of 9 grade I-II and only 2 of 9 grade IV. The median donor age was very young with 74 months (range 20-240 months) and 10 of 17 were sex matched. Thus absence of GVHD risk factors in young children could be the major obstacle in achieving an anti-tumor effect with allogeneic BMT in neuroblastoma.

Bone Marrow Transplantation↗
PubMed1993

Curability of relapsed childhood B-cell non-Hodgkin's lymphoma after intensive first line therapy: a report from the Société Française d'Oncologie Pédiatrique.

The very high cure rate in advanced B-cell non-Hodgkin's lymphoma in children using intensive multiagent therapy has been previously reported by the French Sociéte Française d'Oncologie Pédiatrique lymphoma Malin B type (LMB) group. To address the issue of salvageability in an unselected group of patients who had all received the same front-line therapy, the outcome of relapses following the LMB 84 (216 patients) protocol have been reviewed. Fourteen percent of patients achieving complete remission (CR) relapsed, ie, 27 of 195. Relapse sites comprised the central nervous system (CNS) alone (6 cases), lung or mediastinum (2 cases), abdomen (8 cases), head and neck (2 cases), or multifocal (9 cases). There were three early deaths due to disease. Twenty-four patients received rescue chemotherapy regimens and 15 were treated with high-dose chemotherapy and bone marrow rescue (1 allogeneic). Of these, 9 were in second CR, 4 in second partial remission, and 2 treated during progressive disease. One died in CR from treatment-related toxicity. Ten relapsed postbone marrow transplant and 4 are alive disease free and probably cured. Two of the long-term survivors had some delay during initial chemotherapy due to toxicity and two were isolated CNS relapses. Twelve of 27 patients did not proceed to megatherapy (12 of 12 died).

Bone Marrow↗
PubMed1993

Double megatherapy and autologous bone marrow transplantation for advanced neuroblastoma: the LMCE2 study.

In the LMCE1 study using a single course of megatherapy most of the relapses occurred during the first 2 years after autologous bone marrow transplantation. A second pilot study (LMCE2) was therefore set up using a double harvest/double graft approach with two different megatherapy regimens. Objectives were to test the role of increased dose intensity on response status, relapse pattern and overall survival. Thirty-three patients (20 boys, 13 girls) with a median age of 53 months at first megatherapy (range, 17-202 months) entered this study. They were cases either with refractory disease in partial response after second line treatment for stage 4 neuroblastoma (n = 25) or after relapse from stage 4 (n = 5) or stage 3 disease (n = 3). All patients received Etoposid and/or Cisplatinum (or Carboplatin) containing treatments before megatherapy. The first megatherapy regimen was a combination of Tenoposid, Carmustine and Cisplatinum (or Carboplatin), the second applied Vincristin, Melphalan and Total Body Irradiation. The first harvest was scheduled 4 weeks after the last chemotherapy, the second 60 to 90 days after megatherapy. All marrows were purged in vitro by an immunomagnetic technique. Median follow up time since first megatherapy is 56 months. Response rates for evaluable patients were 65% (complete response rate: 16%) for megatherapy 1 and 60% (complete response rate: 25%) for megatherapy 2. Considering that only patients with delayed response or relapse were eligible for this pilot study the overall survival was encouraging with 36% at 2 years and still 32% at 5 years. The costs for these survival rates were high in terms of morbidity (four early and four late toxic deaths; toxic death rate: 24%). Double harvesting may have the disadvantage of delayed engraftments related in part to a disturbance of marrow microenvironment by megatherapy 1. This double megatherapy approach achieved a prolonged relapse free interval (median 11 months, range 2-31 months) in patients reaching megatherapy 2 and justifies further evaluation of concepts with consecutive dose-escalation.

Adolescent↗
PubMed1993

Etoposide in relapsed or refractory Wilms' tumor: a phase II study by the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group.

PURPOSE: Despite a high cure rate of approximately 85% in Wilms' tumor by multimodality therapy, to date only four drugs are known to be active against such tumors. There is a clear need for new active drugs. PATIENTS AND METHODS: Thirty-one patients with relapsed or refractory Wilms' tumor from three British and 14 French centers were treated with intravenous (IV) etoposide 200 mg/m2 daily for 5 days. Original stage was I (n = 3), II (n = 7), III (n = 9), IV (n = 10), and V (n = 2). Prior chemotherapy, administered initially or at relapse, included vincristine and dactinomycin in all cases, doxorubicin or epirubicin in 30, and ifosfamide in 20. Sites of relapse or resistant disease were lung in 13, abdomen or pelvis in six, liver in one, and multiple in 11. When entered onto the study, 12 patients were in first relapse, 10 in second relapse, and four in third or more relapse. Five had never obtained a complete remission. All but two (progressing) patients received two courses of etoposide, the second course being administered at day 21. RESULTS: A complete response (CR) was documented in two patients, partial response (PR) in 11, stable disease in 10, and progressive disease (PD) in eight. The duration of response could not be evaluated, because all responding patients were subsequently treated with multimodality therapy. The major toxicities observed were neutropenia and thrombocytopenia, but most patients had been heavily pretreated. No toxic death clearly associated with etoposide was noted. CONCLUSION: It is concluded that etoposide in this schedule is an active agent in Wilms' tumor and should be considered for inclusion in regimens for high-risk patients, such as those with metastatic disease at diagnosis and those who relapse after multiagent chemotherapy.

Adolescent↗
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↗