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Biomedical subjects

M Favrot

Publications and source records attributed to M Favrot.

At least 37 records · Page 2Linked to original sources
PubMed1996

Restriction of the T-cell repertoire in tumor-infiltrating lymphocytes from nine patients with renal-cell carcinoma. Relevance of the CDR3 length analysis for the identification of in situ clonal T-cell expansions.

Renal-cell carcinoma (RCC) is one of the human cancers which respond best to immunotherapy. To better characterize the mechanism of the immune response in RCC, we analyzed the T-cell receptor (TCR) beta-chain repertoire in primary RCC, metastases and paired peripheral blood lymphocytes (PBL) from 9 patients. For 3 of these, we analyzed T cells recovered from normal kidney, or from tumor-involved lymph nodes as well as tumor-infiltrating lymphocytes (TIL) expanded in vitro for adoptive immunotherapy. The initial semi-quantitative RT-PCR method for definition of the Vbeta gene usage was not informative enough to distinguish intratumoral clonal T-cell expansions. In contrast, the length pattern analysis of the complementary determining regions 3 (CDR3) allowed oligoclonal T-cell populations to be detected in fresh TIL form the 9 patients with RCC. Furthermore, these oligoclonal TIL populations were not present in normal renal tissue, autologous PBL or tumor-involved lymph nodes. Different clonal T-cell expansions were identified in the primary tumor and in a pulmonary metastasis from the same patient. The detection of clonal T-cell populations observed in RCC suggests an in situ expansion in response to potential tumor antigens. This report provides an overall and accurate description of the T-cell repertoire in a significant number of samples from patients with RCC.

Carcinoma, Renal Cell↗
PubMed1995

Intensive regimen of cytokines with interleukin-2 and interferon alfa-2b in selected patients with metastatic renal carcinoma.

We conducted a Phase II trial using an intensive regimen combining interleukin-2 (IL2), interferon-alfa-2b (IFN), and lymphokine-activated killer (LAK) cells. The aim of this study was to evaluate the toxicity and the efficacy of this combination in selected patients with metastatic renal cell carcinoma. Thirty-one assessable patients were treated with at least one cycle of a regimen consisting of 20 x 10(6) IU/day s.c. IFN for 5 days, followed 2 days later by i.v. injections of 24 x 10(6) IU/m2/day IL2 every 8 h together with i.v. bolus of 5 x 10(6) IU/m2/day IFN every 8 h during 5 days. After a 6-day break, during which four leukophereses were performed, this i.v. combination was administered along with the LAK cell reinjections for a maximum of 5 days. Twenty-seven patients underwent the two parts of the first course of treatment; respectively, 42% and 46% of the planned dose of IL2 and IFN were administered. Several severe toxicities were observed including two treatment-related deaths. Significant tumor responses were observed in seven patients, including two complete remissions. Two of these patients remain alive without evidence of disease 36 and 40 months after treatment, respectively. This intensive regimen of IL2 together with IFN and LAK cells cannot be recommended even in selected patients with metastatic renal cell carcinoma. In addition, our results argue against the concept of a dose-response relationship in this setting.

Adult↗
PubMed1995

CD34+ cell immunoselection from G-CSF-alone-primed peripheral blood in children with low body mass.

We report the data of CD34+ cell immunoselection from peripheral blood after G-CSF-alone mobilization (10 micrograms/kg/d s.c.) in nine children with neuroblastoma (median age 4-5 years (2-8), median body weight 16 kg (10-20). Leukaphereses were carried out on a Cobe Spectra separator and two consecutive harvests (4 blood volumes processed) were used for immunoselection on a Ceprate column. The yield of CD34+ cells in the purified fraction was 50% (23-80), with a median number of 2.8 x 10(6) CD34+ cells/kg (1-9.4). All patients were reinfused with selected CD34+ cells after busulfan 600 mg/m2 +melphalan 180 mg/m2 and achieved successful haemopoietic recovery.

Antigens, CD34↗
PubMed1994

Oligoclonality of tumor-infiltrating lymphocytes from human melanomas.

A PCR-based method that determines VDJ junction size patterns in 24 human TCR V beta subfamilies was used to analyze T cells infiltrating sequential malignant melanoma biopsies for the presence of clonal expansions. Infiltrating T cell populations were found to present clonal expansions over a more or less complex polyclonal background. Two clones from a single patient were sequenced and detected in three different tumor sites (skin biopsies), whereas only one of them was also present in peripheral blood. Biopsies from this patient did not show major repertoire changes during in vivo IL-2 treatment. In contrast, in biopsies from a second patient, the expression of all the detected V beta subfamilies was increased and a larger number of clones expanded, probably as a result of therapy. A similar evolution was found among infiltrating T cells cultured in vitro from a third patient for several weeks in the presence of IL-2, where the largely polyclonal repertoire of fresh T cells (from invaded lymph nodes) was dramatically reduced to mainly clonal expansions in all V beta subfamilies detected. The high resolution method used here enables a rapid, comprehensive, qualitative, and semiquantitative description of the T cell repertoire of heterogeneous cell populations. Its use in conjunction with a functional analysis of clones detected within these populations should provide a better understanding of the evolution of the T cell repertoire among tumor-infiltrating lymphocytes during the progression of the disease and as a response to immunotherapy.

Base Sequence↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment.

PURPOSE AND METHODS: Based on preliminary experience, there was a need for modifications and clarifications in the International Neuroblastoma Staging System (INSS) and International Neuroblastoma Response Criteria (INRC). In 1988, a proposal was made to establish an internationally accepted staging system for neuroblastoma, as well as consistent criteria for confirming the diagnosis and determining response to therapy (Brodeur GM, et al: J Clin Oncol 6:1874-1881, 1988). A meeting was held to review experience with the INSS and INRC and to revise or clarify the language and intent of the originally proposed criteria. Substantial changes included a redefinition of the midline, restrictions on age and bone marrow involvement for stage 4S, and the recommendation that meta-iodobenzylguanidine (MIBG) scanning be implemented for evaluating the extent of disease. Other modifications and clarifications of the INSS and INRC are presented. In addition, the criteria for the diagnosis of neuroblastoma were modified. Finally, proposals were made for the development of risk groups that incorporate both clinical and biologic features in the prediction of prognosis. The biologic features that were deemed important to evaluate prospectively included serum ferritin, neuron-specific enolase (NSE), and lactic dehydrogenase (LDH); tumor histology; tumor-cell DNA content; assessment of N-myc copy number; assessment of 1p deletion by cytogenetic or molecular methods; and TRK-A expression. RESULTS AND CONCLUSION: Modifications of the INSS and INRC made at this conference are presented. In addition, proposals are made for future modifications in these criteria and for the development of International Neuroblastoma Risk Groups.

Humans↗
PubMed1993

[Neuroblastoma in children: clinical and biological aspects. An experience of screening in France].

Neuroblastoma is the commonest solid tumour in children under the age of 5 years (50% of cases before 2 years, 90% before 5) and the second cause of death after accidents. Approximately one child in 10,000 develops neuroblastoma by the age of 15 years. The situation in other European and North American countries is similar to that in France. As neuroblastoma is derived from the sympathetic nervous tissues, it is associated with the production of large amounts of catecholamines and their metabolites which are excreted in the urine. Less than 5% of cases do not produce catecholamines. Vanillylmandelic acid (VMA), homovanillic acid (HVA) and dopamine (DA) are the most useful chemical markers for the diagnosis and clinical control of neuroblastoma. They are generally measured using the reliable and sensitive high pressure liquid chromatography (HPLC). Survival is related to stage (the Evan's staging protocol has been superseded by the INNS staging), and age at diagnosis. There is almost 100% survival for stages I and IIa before the age of 12 months, and less than 20% for stage IV when diagnosed after 2 years of age. Multiple copies of the N-myc oncogene, deletions of chromosome 1p, and diploidy in tumour cells are associated with poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

[Breaking the isolation. Telecommunication in the service of schooling of sick children].

We describe here a two-way teleconferencing system which links the sterile and pediatric units of the Center for Cancer Treatment in Lyon to a secondary school and the pediatric unit of the University Hospital Edouard-Herriot where primary teaching is given. Léon-Bérard Center and Edouard-Herriot Hospital are 300 m apart. Elie-Vignal secondary school is 6 km from the first site; all three institutes are connected through hyperfrequency aerials. With the help of this system, communication (voice and image) between children in hospital and pupils or teachers in school is instantaneous. Children in bed can listen to the lesson, break in on the conversation in school, ask questions or answer those of teachers. After school time, the system can also be used to organize games between children, or friendly contacts between children in each institute, children in the college, brothers, sisters or friends who may have access to one of those institutes. The system aims are: 1) to improve the education delivered to children and teenagers who spend long periods in hospital; 2) to establish a relationship between both worlds of healthy or sick children through teaching and playing in common; 3) finally, to facilitate the social insertion of sick children at leaving hospital.

Adolescent↗
PubMed1992

[Gene transfer and gene therapy].

The application of gene transfer technology to human gene therapy has been intensively investigated during the last decade. The first human clinical trials in adenosine deaminase deficiency and metastatic melanoma recently demonstrated the feasibility and safety of using retroviral gene transduction for human gene therapy. Many problems remain to be solved for a better understanding of the functioning of genes to be transferred, a better efficiency of gene transfer and genetic correction by site-specific targeting in vivo, a better knowledge of the biological properties of target cells such as totipotent hematopoïetic stem cells. Clinical developments are expected in genetic diseases (immunodeficiency, thalassemia, hemophilia) and non genetic disorders (lymphokine gene therapy for cancer).

Child↗
PubMed1992

[Retinoblastoma].

Retinoblastoma (RB) is the most frequent ocular tumor in childhood. Due to recent advances in molecular biology, RB has become a study model for cancer suppressor genes, and antenatal diagnosis has now become feasible. The goals of therapy include an improved survival rate, decrease in iatrogenic sequelae (especially enucleation), and avoidance of radio-induced neoplasias. This review examines recent data from the literature.

Child↗
PubMed1992

[To break the isolation. Telecommunication to help the schooling of sick children].

A 2-way teleconferencing system has been described which links the sterile and pediatric units of the Center for Cancer Treatment in Lyon to a secondary school and the pediatric unit of the University Hospital Edouard Herriot where primary teaching is given. The Léon Bérard Center and Edouard Herriot Hospital are 300 m apart. Elie Vignal secondary school is 6 km from the first site; all three establishments are connected via hyperfrequency aerials. With the help of this system, communication (voice and image) between children in hospital and pupils or teachers in school is instantaneous. Children in bed can listen to the lesson, break in on the conversation in school, ask questions or answer those of teachers and play with children in the classroom. The aims of the system are: 1) to improve the education delivered to children and teenagers who have to spend long periods in hospital; 2) to establish a relationship between the worlds of healthy and sick children through teaching and playing in common; 3) to facilitate the social insertion of sick children after leaving the hospital.

Adolescent↗
PubMed1992

[Analysis of changes in serum levels of TNF, IL-1 and IL-6 during administration of IL-2. Correlation with clinical response to treatment].

We have investigated the serum concentrations of TNF, IL-1 and IL-6 in 49 patients with metastatic renal carcinoma receiving interleukin 2 (IL-2) or a combination of IL-2 and interferon alpha (IFN). Our results demonstrate that IL-2 and/or IFN induce an increase of serum concentrations of IL-1 and TNF in 95% and 75% of the patients respectively. Serum IL-6 levels increase in 44% of the patients. Serum concentrations of IL-1 and TNF remain elevated 48 hours after the end of IL-2 infusion. IL-1 and TNF levels are higher in patients receiving a combination of IL-2 and IFN. TNF and IL-1 levels in serum are significantly higher in responders to IL-2 treatment 48 hours after the end of IL-2 infusion. These two biological criteria enable a subgroup of patients with a very low response rate to IL-2 to be defined. The persistent increase of these cytokines in serum indicates a persistent activation of the immune system lasting after the end of IL-2 treatment which could be involved in the antitumor response.

Adenocarcinoma↗