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M C Favrot

Publications and source records attributed to M C Favrot.

71 records · Page 4Linked to original sources

Use of a liquid cell culture assay to quantify the elimination of Burkitt lymphoma cells from the bone marrow.

A new liquid cell culture assay for propagating Burkitt lymphoma (BL) cells in the presence of excess allogeneic irradiated bone marrow (BM) has been standardized. The Burkitt cell lines used in this assay were newly established from the tumours of our patients and were either EBV(+) or EBV(-). The phenotypic characteristics of lines were similar to those of the original malignant tumours. With the help of this liquid assay it was possible to evaluate the efficacy of in vitro procedures designed to completely eliminate malignant cells from harvested BM prior to autologous transplantation (i.e., immunomagnetic depletion or antibody-complement-mediated cytolysis). With six out of the seven cell lines tested, the assay permitted the detection of as few as one BL cell in 4 X 10(6) normal BM cells and the measurement of up to 5 log BL cell elimination from 1% contaminated samples.

Antibodies, Monoclonal↗

[Detection of residual cells contaminating the bone marrow in neuroblastoma. Apropos of 80 bone marrow evaluations].

Eighty bone marrow studies (each including 4 aspirates and 4 trephine biopsies) were performed in 37 children with stage IV neuroblastoma to assess the most accurate means for detection of invasion by neuroblastoma cells. Among 38 abnormal results, only trephine biopsy(ies) were found positive in 24 cases (63%), only aspirate(s) in 5 cases (13%), and both in 9 cases (24%). In 37% of abnormal results, only 1 of the 8 tests performed was found positive. No benefit was obtained from either associated touch imprints of iliac biopsies (67 investigations), or exploration of extra-iliac sites (66 sternums, 53 tibias). Two monoclonal antibodies, claimed to be specific for detection of neuroblastoma cells in bone marrow, were used in 56 investigations; they could detect minimal residual disease in some cases, but they were unreliable when no staining was obtained if initial phenotype of neuroblastoma had not been assessed, or when few isolated cells were observed. Prospective studies using immunocytology and immunohistology are thus warranted.

Antibodies, Monoclonal↗

Detection of minimal malignant cell infiltration in the bone marrow of patients with solid tumours, non-Hodgkin lymphomas and leukaemias.

Detection of a minimal malignant cell infiltration is becoming essential in oncohaematology, either as a prognostic factor in solid tumours or as a criterion of response to therapy in both haematological and non-haematological malignant proliferations. Evaluation of the efficiency of new therapeutic protocols, especially those involving high-dose chemotherapy and allogeneic or autologous bone marrow transplantation, requires agreement between the different investigators on the definition of minimal residual disease in the bone marrow, on the limits of detection of the various available methods and on the types of investigations required in each clinical situation. This report summarizes the conclusions reached at the First France-Autogreffe Meeting on Minimal Residual Disease in the Bone Marrow.

Acute Disease↗

[Cardiotoxicity of anthracyclines in children. Contribution of anthracyclines in pediatric oncology].

Anthracyclines induced cardiotoxicity in children remains a major problem. Classical data are found: cumulative dose, way of injection, anterior cardiopathy, cardiac area irradiation, interaction with other cytotoxic drugs ad age. 2 kinds of disorders are recorded: 1) Acute rhythmic dysfunctions, early and often transitory; 2) congestive heart failure often not reversible and depending on total dose. Prognostic is still poor and intricate with prognostic of the tumor. Over all incidence is 2.7%. Very young children seem to be more sensitive. Continuous infusion is less toxic than IV bolus. Studies with new anthracyclines are yet uncommon but seems to be comparative with adult literature. Monitoring is identical to adults. EKG is of minor interest. Endomyocardial biopsies have been reported. There is no prognostic value of ultrasound tomogram, but exercise echocardiography can be performed. Nuclide fraction ejection is more reliable.

Adolescent↗

EBV-negative and -positive Burkitt cell lines variably express receptors for B-cell activation and differentiation.

The expression of receptors for proliferation and differentiation factors was analyzed by indirect immunofluorescence on 29 Burkitt lymphoma (BL) cell lines previously classified into 3 groups on the basis of their reactivity with 8 monoclonal antibodies (MAbs), including anti-CALLA, BL13 and TU1. BL13 and HB5 antibodies recognize different epitopes of the EBV/CR2 receptors. The determinant recognized by BL13 has been previously shown to be expressed only on cell lines of the first two groups, supposed to derive from the germinal center and to be negative on a third group of lines of putative BM origin and established from sporadic cases of BL. In contrast, and as expected from its reactivity on normal B cells in the BM or in the lymph nodes, HB5 antibody reacts with all BL lines except one. The receptor for transferrin is expressed on the 29 lines. Two new MAbs, Bac-1 and B1H5, could recognize respectively receptors for BCGF1 and BCGF2. Bac-1 reacts with 15 of 17 BL lines belonging to the first two groups and 7 of 12 BL lines of the third group; 14 of 15 EBV + lines express Bac-1. No BL line expresses B1H5. The IL2 receptor is weakly expressed on 5 EBV + cell lines and one EBV (-) line. All delta are BCGF1-positive. The almost constant expression of BCGF1 receptor on EBV + cell lines is the only strict relation between the expression of receptors for growth factors and their characteristics (i.e. EBV association, translocation, ethnic origin and clinical presentation). The maturation stage or the origin of BL cell lines in relation to the expression of growth factor receptors and the functional significance of these receptors will be discussed.

Antigens, Neoplasm↗

Histological, cytological and immunological analyses are complementary for the detection of neuroblastoma cells in bone marrow.

On 80 occasions 4 iliac biopsy trephines and 4 iliac aspirations were performed in 37 children with neuroblastoma at various stages of the disease. In 38 of these procedures, tumour cells were detected. In 24% of cases, both trephines and aspirates were positive, whereas in 63% neuroblastoma cells were detected only on the trephines and in 13% only on the aspirates. In addition, in 37% of the stagings, only one out of the 8 investigations was abnormal. Only in one of 33 pathological cases, was BM involvement diagnosed on trephine imprint. No involvement was ever observed on tibial and sternal aspirates without iliac involvement. Immunological studies with two monoclonal antibodies HSAN 1-2 and UJ13A were performed on 56 occasions. Cytohistological and immunological studies were concordant in 39. In 3 studies, the antigens recognized by the two monoclonal antibodies were not expressed by the initial tumour and in 3 additional studies immunological results were falsely negative; but in 11 cases monoclonal antibodies identified residual malignancy despite normal cytohistology. From this study, biopsies appear more helpful to detect malignant cells than aspirates. Immunological staining clearly leads to a better definition of tumour cells in aspirates.

Biopsy↗

Bone marrow purging procedure in Burkitt lymphoma with monoclonal antibodies and complement: quantification by a liquid cell culture monitoring system.

Using B1, Y29/55 and AL2 monoclonal antibodies (MoAbs) to target Burkitt lymphoma (BL) cell lines, we defined optimal conditions to lyse, in the presence of baby rabbit complement, BL cells in excess bone marrow (BM). After the purging procedure, down to one residual BL cell in 10(6) normal ones was detectable with a liquid cell culture assay. Using a cocktail of three MoAbs, on five different cell lines were observed more than 4 log BL cell depletion in samples contaminated with 1% BL cells and only one failure of the procedure on 17 experiments. However, a sixth line was constantly resistant to the procedure.

Animals↗

Indication for bone-marrow harvesting and purging in Burkitt's Lymphoma: a three-year experience.

Between 1980 and 1983, 317 bone-marrow (BM) aspirates from 63 cases of Burkitt's lymphoma (BL) were studied with an in-vitro liquid culture monitoring system. BL cell lines were obtained in culture from 14 of 15 patients with cytologically positive marrow. The in-vitro monitoring system was shown to be useful regardless of Epstein-Barr virus (EBV) status, clinical status of patients and cytogenetic anomalies (8 t(8;14) 2 t(8;22) 2 When BM was cytologically normal or suspect, i.e., less than 5% BL cells, the in-vitro monitoring system was shown to be more sensitive than cytological examination in 25 of 56 cases (44%). The sensitivity of the test is 1/100 000, i.e., 3 logs inferior to the level of detection by cytology. When BM was harvested from all patients in complete remission after two months of chemotherapy, marrow purging proved not to be necessary (38/38 negative cultures); 7/10 of those patients will have been harvested to no purpose (no more than 30% with indication for autologous BM transplantation). When BM was harvested at relapse or in partial remission, the purging procedure was shown to be necessary in 9 of 16 cases (56%).

Bone Marrow↗

Study of blood lipids in 30 children with a malignant hematological disease or carcinoma.

Levels of total lipids, cholesterol and triglycerides were followed in 30 children with malignant hematological diseases, or solid tumors; in addition, chylomicrons, VLDL, LDL and HDL were separated by electrophoresis on polyacrylamide gel. Nine of the 13 children with acute lymphoblastic leukaemia presented an increase of triglycerides and VLDL at time of diagnosis; all other parameters (cholesterol, HDL, LDL, chylomicrons) were normal. The lipid profile went back quickly to normal when hematological remission was obtained and remained stable throughout the course of the disease whatever the evolution might be. Five more patients in relapse were studied and did not present abnormalities. Similar results were obtained in 1/2 patients with acute myeloblastic leukaemia and in 3/5 patients with lymphoma. No lipid profile abnormality was observed in four patients with solid tumor and in one patient with histiocytosis X. The values of triglycerides and VLDL in pathological cases will be given. The endogenous nature of this disturbance is discussed as well as its relation with the rate of malignant lymphoid proliferation.

Apolipoproteins↗

Distinct reactivity of Burkitt's lymphoma cell lines with eight monoclonal antibodies correlated with the ethnic origin.

Twenty-eight Burkitt's lymphoma(s) (BL) cell lines were analyzed with anti-human immunoglobulins and monoclonal antibodies: Y29/55, B1, and BA1 are slightly different pan-B-reagents; TU1 and BL13 are two discriminating markers of the follicle; RFT1 is a pan-T-reagent expressed on the follicle mantle; AL2 reacts with the common acute lymphoblastic leukemia antigen gp100; and 38:13 recognizes a BL-associated antigen. Those lines were classified into 3 groups according to their membrane phenotype. In the first 2 groups, cell lines were derived from BL of germinal center origin, whereas in the last group they were established from BL cells originating in the bone marrow. All cell lines in the last group were from Caucasian BL, whereas lines from African BL of a high-incidence area were in group 1. North African cases were in group 2. Those distinct subgroups were not related specifically to the reactivity with Epstein-Barr virus nuclear antigen, the type of chromosomal translocation, or the clinical features. The variations induced by growth culture as well as the clinical implications were discussed.

Antibodies, Monoclonal↗

Can MIBG scan replace the need for bone marrow assessment at diagnosis and reassessment in stage 4 neuroblastomas?

UNLABELLED: Complete staging (extensive marrow investigation and meta-iodo benzylguanine (MIBG) scan) is considered as mandatory both at diagnosis and after chemotherapy for assessment of metastases in neuroblastomas. However the correlation between bone marrow invasion and uptake of MIBG at metastatic sites remains unclear. This study investigates whether MIBG alone is sufficiently sensitive to make these procedures redundant. PATIENTS AND METHODS: 20 children over one year of age, with histologically proven metastatic neuroblastoma were studied. Extensive bone marrow assessment and MIBG bone scan performed both at diagnosis and after completion of induction chemotherapy were reviewed. RESULTS: At diagnosis metastases were detected by marrow investigation alone in 2, MIBG alone in 2 and both procedures in 16. After induction chemotherapy metastases were detected by only marrow investigation in 2, by only MIBG in 3, by both procedures in 6 patients, and by none in 9. CONCLUSIONS: Whether marrow investigations and MIBG scan explore the same phenomenon remains unclear. However it appears that marrow disease that is histologically detectable may remain MIBG negative both at diagnosis and after treatment. Both procedures are still justified at time of diagnosis and evaluation of response.

3-Iodobenzylguanidine↗

Expression of integrin and CD44 adhesion molecules on neuroblastoma: the relation to tumor aggressiveness and embryonic neural-crest differentiation.

The immunohistological expression of integrins and CD44 cell adhesion molecule was analyzed on neuroblastoma (NB) specimens to study the potential role of these molecules in normal differentiation and in the transformation of neural crest derivatives. None of the specimens expressed the alpha 5 beta 1 integrin heterodimer; the expression of alpha 3 beta 1 heterodimer was maintained during all stages of differentiation; alpha 1 beta 1 heterodimer was expressed on undifferentiated neuroblasts and on Schwann cells, but was lost on ganglion cells. In contrast alpha 2 beta 1, alpha 6 beta 1, alpha 6 beta 4 and alpha V beta 1 expression was usually restricted to cells differentiated in the Schwann cell lineage. Alpha V beta 3 was expressed on tumors developed in the mediastinum. CD44 was strongly detected on differentiated ganglioneuroblastomas, stage 1 and 2 ganglioneuromas, as well as low-grade stage 4S NB and normal neuroblasts migrating in the fetal adrenal gland. CD44 expression was observed on Schwann cells and ganglion cells; in contrast, it was expressed on only 50% stage 3 and 4 undifferentiated NB. None of these specimens expressed exons V5, V7 or V6. In a few specimens, an intracellular expression of exons V8-V10 was observed in ganglion cells. The expression of CD44 on NB may reflect its pattern of expression on sympatho-adrenal precursors and arrest differentiation at these stages. Conversely, CD44 expression may be silenced during malignant transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Gene therapy: a review 6 years after the first trials in man. Round Table No 6 at Giens XIII].

The first protocol of gene therapy was started in 1990 for two children with adenosine deaminase deficiency. In 1997, the field largely widened, with 2100 patients treated: 10 per cent suffer from hereditary disease, cystic fibrosis mainly, and 90 per cent acquired disease, mainly cancers or HIV infection. No toxicity of gene therapy has been observed for the patients or their environment. A psychological barrier has been crossed which might allow an easing of the regulations. Industrial firms are heavily engaged in this field and are defining the rules of production and use. After in vivo administration to patients, the gene is expressed but the vectorisation is still very weak. Gene therapy should thus be limited to indications with a well-established clinical and scientific rationale.

Child↗