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Biomedical subjects

T Philip

Publications and source records attributed to T Philip.

At least 145 records · Page 8Linked to original sources

[Constitutional translocation t(1;6) and Burkitt's lymphoma].

BACKGROUND: The relationship between constitutional chromosome aberrations and a predisposition to malignancy has already been established. CASE REPORT: A 4 year-old boy was admitted suffering from abdominal mass. Biopsies of the tumor and bone marrow showed a stage IV Burkitt's lymphoma. Karyotype showed a constitutional t(1;6)(p36;q22) in initial bone marrow samples and peripheral lymphocytes. No classic Burkitt's type translocation was demonstrated in the malignant bone marrow cells. CONCLUSION: Our case is similar to four other reported cases. The break-points 1p36 and 6q22 seem to be involved in several malignant tumors, especially lymphomas.

Burkitt Lymphoma↗

[Economic evaluation of screening for neuroblastoma].

Though neuroblastoma, a cancer occurring in children, is infrequent, several countries run screening programs to detect it early since advanced stages show high mortality rates. The aim of this study is to propose a non empirical medico-economic evaluation model for the screening program for neuroblastoma, adaptable to various contexts. A marginal cost-effectiveness analysis was performed. The effectiveness and cost criteria were respectively the number of children who do not die from neuroblastoma and the cost of the screening programs, together with the cost of the treatments. The major parameters of the model were: size of target population, incidence, over-incidence rate, compliance rate, test sensitivity, distribution of cases and mortality rates according to the stage of the disease. The aim of the model was to determine, within a specific context (fixed parameters), the cost of an additional life saved, or less pragmatically to calculate the threshold values for the parameters for which the screening program for neuroblastoma is worthwhile (ie marginal cost equal to zero). We illustrate this model presentation with simulations elaborated from the neuroblastoma screening program performed in the Rhône area, France.

Child, Preschool↗

Value of autologous bone marrow transplantation in follicular lymphoma: a France Autogreffe retrospective study of 42 patients.

The value of high-dose chemotherapy with hematologic stem cell rescue has not been established in the treatment of low-grade non-Hodgkin's lymphoma. We report the results of a retrospective 'France Autogreffe' study of 42 patients grafted in first partial remission (n = 13) or chemosensitive relapse (n = 29) for follicular lymphoma before January 1990. The median age was 38 years (range 26-61 years). Preparative therapy was chemotherapy alone in 22 patients and total body irradiation (TBI)-containing regimens in 20 patients. Thirty-seven patients received hematopoietic marrow stem cells. Bone marrow purging was performed in 15 patients. Five patients received peripheral blood stem cells. Three patients died of bone marrow transplantation toxicity and two others died in complete remission 10 months after autologous bone marrow transplantation. With a median follow-up of 43 months, relapse-free survival is 60%, event-free survival 58% and overall survival 83%. To date no prognostic factors have been shown.

Adult↗

[Malignant lymphoma in children].

Malignant lymphomas of children are among the pathologies which have benefited the most of the improvements of therapy since twenty years. Classically, the therapy of Hodgkin lymphoma included radiotherapy; nowadays, the role of chemotherapy becomes more important. For non-Hodgkin lymphomas, the role of surgery and radiotherapy has quite completely disappeared, and the tumors are cured by chemotherapy. This review will focus on Hodgkin lymphoma, and two of the most frequent non-Hodgkin lymphomas, namely Burkitt lymphoma and lymphoblastic lymphoma. Most recent advances in treatment and management of sequelae are presented.

Adolescent↗

[Management, quality of life and social rehabilitation of the child with cancer].

The aim of the treatment of a child with cancer is to reach cure without physical and/or psychological sequelae. The quality of life should be preserved by a global approach of the child and his family from the diagnosis until completion of treatment and follow-up periods. The specialist and the general practitioner should inform the child and his family on a regular basis, and check prospectively the tolerance of the siblings. The role of physicians also includes a fight for better information of public, economical and political powers, so that a cured child may become an happy, well integrated adult.

Age Factors↗

[Desmoplastic tumors with multiple differentiation. A new entity. Six cases].

Desmoplastic tumours with divergent differentiation are principally located in the abdomen and develop locally or regionally. They occur in adolescents or young adults and are characterized at histology by a proliferation of undifferentiated small cells surrounded by a dense stroma. Only immuno-histo-chemistry provides the diagnosis. Since their chemosensitivity is rare and often partial the outcome is usually lethal. Six new cases of this recently described entity are presented here. The authors are in favour of a multidisciplinary and aggressive management, combining intensive polychemotherapy, extensive surgical exerisis and total abdominal radiotherapy.

Abdominal Neoplasms↗

Serum interleukin-10 in non-Hodgkin's lymphoma: a prognostic factor.

Serum interleukin-10 (IL-10) was measured retrospectively in 153 patients with a fully documented history of non-Hodgkin's lymphoma (NHL) using an enzyme-linked immunosorbent assay (ELISA) detecting both human IL-10 and the Epstein-Barr virus (EBV) molecule BCRF1/viral IL-10. IL-10 was detectable in 47 (46%) of the 101 patients with active NHL, 3 of 52 (6%) patients in first partial or complete response, and none of the 60 healthy blood donors. Serum IL-10 was detectable with a similar frequency in all subtypes of NHL and in all clinical stages, as well as in EBV-seropositive and EBV-negative patients. In patients with intermediate or high-grade NHL, the presence of detectable serum IL-10 at diagnosis was correlated to a significantly shorter overall (P = .025) and progression-free (P = .030) survival. Patients with stage IV disease and detectable serum IL-10 had a particularly poor prognosis (4 years of survival: 0%). Multivariate analysis showed that IL-10 was an independent prognosis factor. These results indicate that IL-10 is detectable in a subgroup of patients with active NHL and correlates to a poor survival in patients with intermediate or high-grade NHL.

Adolescent↗

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↗

Phase II study of fotemustine as second-line treatment after failure of immunotherapy in metastatic renal cell carcinoma.

Sixteen patients who after prior systemic immunotherapy had progressing disease received fotemustine (100 mg/m2) i.v. on days 1, 8, and 15 followed by a 5-week rest period. In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 fotemustine given once every 3 weeks until progression on toxicity occurred. No objective response was observed. Four patients showed stable disease (median duration: 4 months; range: 3-19). The main toxicities were neutropenia (WHO grade 3 and 4: 27%) and thrombocytopenia (WHO grade 3 and 4: 27%). Fotemustine was administered on an outpatient basis and was generally well tolerated, but in our series of patients it had no antitumour activity in metastatic renal cell carcinoma after failure of immunotherapy.

Adult↗

Successful treatment for a metastatic supratentorial malignant rhabdoid tumor.

The case of a boy with a familial history of Rendu-Osler disease, who successively developed a cerebellar pilocytic astrocytoma (at 3 years of age) and a metastatic supratentorial malignant rhabdoid tumor (at the age of 12 years) is reported. After a complete surgical removal, the CSF was cleared by 4 courses of chemotherapy, and the child received a craniospinal irradiation. He is currently alive and well 19 months after completion of the treatment. The authors discuss the ethiopathogeny of such intracranial tumors and argue for aggressive treatment.

Astrocytoma↗

High-dose chemotherapy with autologous bone marrow rescue in advanced stage IV neuroblastoma.

In order to better evaluate the role of bone marrow purging procedures in the treatment of stage IV neuroblastoma, two similar groups of patients, prospectively treated during the same period at Léon Bérard Center, Lyon, France, and at Giannina Gaslini Institute, Genova, Italy, were reviewed. 18 children were treated in Lyon with a protocol including induction chemotherapy, surgery and a single course of high-dose chemotherapy followed by purged autologous bone marrow rescue. 21 patients were treated in Genoa with a very similar protocol which did not include purging procedures. Progression-free survival at 6 years was 12% (95% confidence interval 0-24%), without any difference between the two series of patients. The only prognostic factor for long-term survival was the persistence (or not) of bone lesions and the presence of metastatic disease (bone or bone marrow) at graft. The small numbers in the two groups and the very poor outcome make it difficult to conclude on the efficacy of purging.

Antineoplastic Combined Chemotherapy Protocols↗

Indication and limits of megatherapy and bone marrow transplantation in high-risk neuroblastoma: a single centre analysis of prognostic factors.

76 patients with high risk neuroblastoma were treated with one (41 patients) or two consecutive courses (35 patients) of megatherapy. Autologous bone marrow transplantation was scheduled after each megatherapy. Univariate analysis confirmed two prognostic factors in this heterogeneous study population: no bone lesions before megatherapy and age at diagnosis of less than 2 years with 5-year progression-free survival rates of 51% (P < 0.0007) and 53% (P < 0.025), respectively. Both factors were shown to be of independent prognostic significance using the Cox proportional hazard model. Identification of prognostic factors should help to define the interest and limits of megatherapy. We consider that elective megatherapy followed by innovative treatments appears justified in patients with persisting bone disease. In contrast, megatherapy has to be re-evaluated for patients showing a more favourable response pattern and/or young age, ideally in a randomised, prospective trial.

Adolescent↗

Multivariate analysis of prognostic factors in patients with non HIV-related primary cerebral lymphoma. A proposal for a prognostic scoring.

Between 1982 and 1991, 41 patients were treated for non HIV related primary cerebral lymphoma (PCL) in our institute. The purpose of this study was to perform a multivariate analysis of prognostic factors for survival in these patients. The presence of a CSF protein level over 0.6 g l-1 at diagnosis was found to be the most significant unfavourable prognostic factor in univariate analysis and had not previously been reported. Among the five significant prognostic factors at diagnosis, (age over 60 years, performance status--ECOG scale--over 2, memory dysfunction, non hemispheric tumour site, CSF protein level over 0.6 g l-1 at the diagnosis), three independent factors were identified in multivariate analysis: (1) CSF protein level (P = 0.007; RR = 4.7); (2) PS > 2 (P = 0.04, RR = 2.65); (3) age over 60 (P = 0.08; RR = 2.43). Using the regression coefficient of these three parameters, we determined a prognostic index which allowed us to distinguish three risk groups whose theoretical median survival is 4, 20 and 54, months respectively in patients with non HIV related PCL. These results indicate that PCL is an heterogeneous disease in terms of the prognostic in which three subgroups with discriminant survival can be identified.

Adolescent↗

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↗

Patients with metastatic renal carcinoma candidate for immunotherapy with cytokines. Analysis of a single institution study on 181 patients.

This study was performed with the aim of discovering the characteristics and survival of patients with metastatic renal carcinoma who undergo immunotherapy with an Interleukin 2 based regimen. One hundred and eighty-one patients with metastatic renal carcinoma were referred to our institute from October 1987 until August 1991; 129 were treated with Interleukin 2 with or without Interferon alpha in three successive protocols. Fifty-two patients were not treated with immunotherapy due to the exclusion criteria of the protocols. Sixty-four patients with the same disease who had been referred to our institute before the initiation of this programme (1982, 1987) were also analysed as a control group. The main characteristics of the three different cohorts of patients were analysed and compared with univariate statistical tests; the median survival of the patients was calculated and compared. The referral rate increased from 13 a year to 45 a year while the IL2 trials were being conducted. Patients treated with cytokines have a median survival of 18 months after occurrence of metastases, compared to 6 and 8 months, respectively, in excluded patients and the control group. This parameter is of 15 months when the 181 patients, treated with cytokines or not, are considered. The survival of treated vs excluded patients is significantly different (P < 10(-6); so is the survival of the 181 patients recently included when compared to the historical group (P:10(-5). When the 181 recent patients are compared to the historical control group, a number of differences appear in their characteristics, which prevent us from drawing any conclusion about the role of immunotherapy in the improvement of survival observed. This study clearly evidences the selection of the patients receiving immunotherapy and the modification in referrals of a disease induced by a new available therapy. This emphasises the need for prospective studies in this setting.

Adult↗

A comparison of 2 modes of administration of recombinant interleukin-2: continuous intravenous infusion alone versus subcutaneous administration plus interferon alpha in patients with advanced renal cell carcinoma.

PURPOSE: To compare 2 treatment modalities with recombinant Interleukin-2 (rIL-2) for patients with advanced Renal Cell carcinoma (RCC): continuous intravenous infusion (CIV) alone versus subcutaneous (s/c) rIL-2 + Interferon-alpha (IFN-alpha). PATIENTS AND METHODS: Data have been collected on 425 patients with RCC, treated CIV rIL-2 alone, (225 patients), or rIL-2 by the s/c route (200 patients). Patients receiving s/c rIL-2 also received s/c IFN-alpha both drugs being administered on an outpatient basis. Patients receiving CIV rIL-2 were treated as inpatients. Patient eligibility criteria were similar on all studies, and included patients with progressive, advanced disease, but with an ambulatory performance status. RESULTS: The overall response rate for the CIV schedules was not significantly different from the s/c regimens: 15% (95% confidence limits (CL) 10-20%) vs 20% (95%CL 14-26%) with 4% CR in both approaches. Durable responses were seen in both CIV and s/c schedules and there was no evidence of a significant difference in survival in multivariate analysis. There was however an important shift in the toxicity profile. The s/c regimens do not induce a clinically detectable capillary leak syndrome, which is the dose limiting toxicity for CIV regimens. CONCLUSION: Although the introduction of CIV regimens of rIL-2 was a major step forward compared to high-dose bolus, because most patients could be treated in a normal oncology ward, the s/c schedule of rIL-2 + IFN-alpha offers the possibility of outpatient (home) therapy, with no evidence of a reduction in efficacy.

Adult↗