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C Coze

Publications and source records attributed to C Coze.

53 records · Page 3Linked to original sources
PubMed1993

[Bone marrow autograft and cancer in children].

Since about 15 years intensive chemotherapy followed by autologous bone marrow transplantation has been used on the basis of "dose-response" principle to treat certain children with tumours of sombre prognosis. At present, the main indications for this method are metastatif neuroblastoma in less than one-year old children, non-Hodgkin's malignant lymphomas in partial remission or relapse, refractory or recurrent Hodgkin's disease and some peculiar forms of Wilms' tumour. In other tumours, such as rhabdomyosarcoma, Ewing's sarcoma or brain tumours, the indications have not yet been clearly determined. The treatment must be administered as part of multicentre French or European trials conducted in specialized centres. The practice and application of autologous bone marrow transplantation are being revolutionized by the availability of haematopoietic growth factors and the development of the peripheral blood stem cells reinjection technique. Genic therapy will soon have major repercussions in this field.

Bone Marrow Transplantation↗
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

Impact of megatherapy on survival after relapse from stage 4 neuroblastoma in patients over 1 year of age at diagnosis: a report from the European Group for Bone Marrow Transplantation.

PURPOSE: Relapse from stage 4 neuroblastoma usually carries a poor prognosis. A retrospective study using the European Bone Marrow Transplant (EBMT) Solid Tumor Registry was undertaken to define the role of megatherapy (MGT) in relapsed patients. PATIENTS AND METHODS: After relapse, 33 boys and 15 girls with previous stage 4 neuroblastoma received intensification by MGT followed by either autologous (n = 42) or allogeneic (n = 6) bone marrow rescue in 11 European institutions. The median age at diagnosis was 47 months (range, 14 to 134) and the median interval from diagnosis to relapse was 16 months (range, 4 to 94). Thirty patients had received only conventional-dose primary treatments (group A), whereas 18 patients had previously received intensification with MGT (group B). The median follow-up time of the total group is 95 months (range, 25 to 185). RESULTS: The actuarial overall survival rate at 2 years after MGT for relapse is 27% for group A and 0% for group B (P = .02). Three adverse, independent prognostic factors were confirmed by multivariate analysis using the Cox proportional hazards regression model: an interval of less than 12 months between diagnosis and relapse (P < .0001), nonresponding or untreated relapse (P = .0002), and previous MGT during primary treatments (P = .055). None of the other variables analyzed, such as sex, age, bone or bone marrow involvement at diagnosis or at relapse, and type of MGT at relapse, influenced outcome in this patient cohort. CONCLUSION: Responding patients who relapse more than 12 months from diagnosis who had not received previous MGT appear to benefit from consolidation MGT. Relapse patients who do not fulfill these criteria gain no advantage from this cost-intensive procedure and should be treated differently.

Actuarial Analysis↗
PubMed1992

[Ewing's tumor: current knowledge and ignorance].

The diagnosis of Ewing's malignant tumor in the young still raises major problems, either from a clinical point of view because of its rarity, its pluri-potentiality and various symptoms, or on imaging because of its numerous pitfalls. Accordingly the disease is often misdiagnosed as osteomyelitis. Only a high quality biopsy can determine histological diagnosis of undifferentiated small round cell tumor. The chromosomic study shows a specific (11;22)(q24;q12) translocation, and immunocytochemistry and molecular biology show the tumor's neuroectodermal origin. For 20 years, therapy tended toward first line tumor chemoreduction, followed, when appropriate, by complete resection and orthopedic reconstruction of the bone. Radiotherapy, which is responsible for long-term sequelae is now increasingly restricted to inaccessible or incompletely excised tumors. More intensive chemotherapy is being examined in patients with poor prognosis factors such as a negative response to induction chemotherapy, a significant mass or metastases. As a result of new strategies, disease-free survival rate is now between 60-70%. The management of this disease is highly multidisciplinary and patients will now be included in multicentric controlled therapeutic trials. Long term follow-up has to be carried out following completion of treatment.

Adolescent↗
PubMed1992

[Drash syndrome].

The authors report one case of Drash syndrome: association of Wilms' tumor, nephropathy and genital abnormalities. The definition, prognosis and origin of this triad are discussed.

Cadaver↗
PubMed1991

Expression of leucocyte adhesion molecules on 66 clinical neuroblastoma specimens.

LFA-3, ICAM-1, HLA.ABC and HLA.DR expression was analyzed on 66 neuroblastoma specimens. HLA.ABC was expressed on 26 specimens, HLA.DR on 2, LFA-3 on 20 and ICAM-1 on 10. HLA.ABC and LFA-3 were positive on ganglioneuroblastoma or ganglioneuroma, but they were negative on neuroblastoma, independently of the clinical staging; HLA.ABC and LFA-3 were induced in vivo by chemotherapy in parallel with tumoral cell differentiation, in both the primary and the metastases. The expression of ICAM-1 was restricted to 5 of the 10 low-grade stage-1 or stage-2 specimens, 1 stage-3 specimen, and the primary tumors of 2 patients with stage-4 disease, analyzed hence at diagnosis and after chemotherapy (4 specimens); metastatic cells obtained in 1 of these patients were negative. HLA.ABC and LFA-3 expressed on both mycN-negative and -positive specimens, whereas ICAM-1 was restricted to MYCN-negative specimens. LFA-3 diffusely stained partially differentiated neuroblasts, Schwann cells and ganglion cells. The expression of HLA.ABC on differentiated neuroblasts varied from one sample to another and within the same tumor; Schwann cells were strongly positive, but ganglion cells were negative. In positive samples, ICAM-1 was expressed on differentiated neuroblasts and Schwann cells, but negative on ganglion cells; however, most of the differentiated tumors were ICAM-1-negative, suggesting ICAM-1 induction by unknown local signal. The 4 markers were negative on undifferentiated neuroblasts. The distribution of these 4 markers on clinical specimens was in agreement with their reactivity on fetal tissues, as well as with results obtained on neuroblastoma cell lines before and after in vitro treatment with IFN-gamma.

Alkaline Phosphatase↗
PubMed1991

[Medulloblastoma in children. Current treatments and future perspectives].

The various treatments currently available for medulloblastoma are reviewed and modifications which have occurred over the last ten years are analyzed. Surgery is the first step of the treatment of a medulloblastoma. Recent advances in neurosurgical anesthesia and intensive care have substantially improved the quality and extent of exeresis and markedly reduced operative mortality (currently under 2%). Radiotherapy of the entire central nervous system should follow surgery in every case. Use of high energy radiations (together with improvements in surgical treatment) have increased survival rates to 50-60%. However, side effects are frequent. The modalities and timing of chemotherapy have also changed considerably over the last ten years; the different modalities currently used are reviewed, as well as the strategies available for reducing toxic effects and hematologic complications. Currently, chemotherapy is "sandwiched" between surgery and radiotherapy. Treatments under evaluation (monoclonal antibodies, immunotoxins, and immunomodulation) are discussed. The purpose of this therapeutic strategy for medulloblastomas is not only to increase survival rates but, above all, to improve the quality of life in survivors. Close cooperation between health care professionals of the different specialties involved and long term multicenter studies are indispensable if this goal is to be achieved.

Adolescent↗
PubMed1990

Interleukin 2 immunotherapy in children with neuroblastoma after high-dose chemotherapy and autologous bone marrow transplantation.

Four children with persistent neuroblastoma after marrow ablative chemoradiotherapy and autologous bone marrow transplantation received continuous infusion of recombinant interleukin 2, 75 to 120 days after the graft. Recombinant interleukin 2 therapy did not induce any major or nonreversible toxicity, hematological toxicity in particular. One patient entered complete remission for 9 months and a second patient had a long-lasting normalization of urinary catecholamine metabolites with more than 50% regression of bone marrow metastases (8 months). In three children, recombinant interleukin 2 and a second patient entered complete remission for 9 months therapy was followed by major increase and activation of circulating natural killer cells which amounted to 80% of the circulating mononuclear cells.

Bone Marrow Transplantation↗
PubMed1990

[Melanotic neuroectodermal tumor of childhood or melanotic progonoma. Apropos of a case which recurred as an osteogenic tumor].

We are yielding a case of recurring melanotic neuroectodermal tumor of infancy situated in the premaxilla, with a very quick evolution, haemorrhage, and which has precociously recurred after surgical removal. This tumor is studied on the paraclinical (CT scan, M.I.R.) and on the histological hand (immunohistochemical and ultra-microscopy). This observation is then compared with those of literature in which we find about 200 cases. The neurocristopathic histogenesis is actually doing the unanimity. The prognosis must now be quite reserved because of the recurrences (one case for six) and the possibility of malignant forms, some with metastasis.

Connective Tissue↗
PubMed1990

Lymphokine-activated killer cell expansion for clinical trials of adoptive immunotherapy with interleukin-2: optimization of the culture technique.

On leukopheresis products obtained from patients included in a protocol interleukin-2/lymphokine-activated killer (IL-2/LAK) cell therapy, we analyzed, in parallel with the standard culture and on large volumes of these products, different parameters which could either improve LAK cell enhancement or simplify the procedure. We demonstrated first that purification of the mononuclear cells from the leukopheresis product before its culture is not required. An excess of red blood cells and granulocytes (up to 50%) in nonpurified samples improved both the mononuclear cell recovery in short-term culture (4 days) and the activation of LAK cells when the total nuclear cell concentration did not exceed 3 X 10(6)/ml. Different factors can contribute to this enhancing effect: the presence of red blood cells, the liberation of cytokines by granulocytes, or the loss of a population of activated lymphocytes, with liberation of cytokines by granulocytes, or the loss of a population of activated lymphocytes, with larger size and density than resting lymphocytes, during the separation. Supplementation of the medium with 2% heat-inactivated autologous plasma obtained before any treatment rather than with 2% pooled human AB serum does not modify the mononuclear cell recovery in 4-day culture, but it does enhance LAK activity. The inhibitory effect of heat-inactivated autologous plasma on proliferation and activation of LAK cells was never observed, suggesting the absence of suppressive factors in the plasma of the 23 analyzed patients. Similarly, autologous plasma did not modify natural killer and LAK cell functions when added during the cytotoxic assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

A phase-II study of adoptive immunotherapy with continuous infusion of interleukin-2 in children with advanced neuroblastoma. A report on 11 cases.

Nine children with poor prognosis neuroblastoma have been treated by continuous infusion of IL-2 and autologous LAK cells, as described previously by West et al. in adult patients. Six patients were in relapse after high-dose chemotherapy and autologous BMT and three presented with primary refractory disease after conventional therapy. Although patients were very young (median age 6 years; average weight 17 kg), infusion of IL-2, cytapheresis and reinjection of LAK cells appeared feasible with the usual and transient complications observed with IL-2. Haematological toxicity, although reversible, was more important than usually described and due to the presence of bone-marrow metastases in 8 of the 9 patients. Life-threatening toxicity was observed in only one of the admission centres and was probably due to the rapid reinjection of a very large number of activated cells. Two patients presenting with very active disease after high-dose chemotherapy and autologous or allogeneic BMT received IL-2 alone, at 120 days and at 90 days after the graft. The reactivation of grade-II GVHD was the major complication in the patient treated after an allograft, whereas no BMT-related toxicity was observed in the patient treated after the autologous BMT. Immunological modifications induced by IL-2 were very different between these patients. As expected, a preferential outgrowth of NK cells with both NK and LAK activity was observed in the patient treated just after the autograft. In contrast, in the patient treated after an allograft and in the 9 patients in relapse, T lymphocytes remained the major mononuclear cell population with a very large excess of CD8+ T cells. All patients progressed after the first induction cycle with the exception of the only patient treated after autologous BMT who reached a very good partial remission with disappearance of the local tumor and bone metastases. Although very preliminary, these data clearly show that the efficacy of IL-2 largely depends on the patient's immunological status with the optimal effect being observed when IL-2 is given in the first few months following an autograft.

Bone Marrow Transplantation↗
PubMed1989

Analysis of parameters for maximal in vitro proliferation and activation of lymphokine-activated killer cells (LAK).

In 15 patients (11 adults, 4 children) who received IL-2 and LAK cell therapy, we analyzed the different culture conditions which could either improve LAK cell activation and proliferation or which could simplify the procedure. Each parameter was assayed on a large scale and compared to standard culture conditions. Indomethacin had no effects, either positive or negative, on proliferation and activation of the cells. Culturing with 10% AB serum increased proliferation but did not modify total lytic activity compared to 2% AB serum. When cells were cultured in a medium with 2% autologous plasma obtained before any treatment, their proliferation was similar to that obtained in medium supplemented with 2% AB serum but the LAK activity was significantly higher. Autologous plasma obtained at day 8 of treatment (48 h after the first cycle of IL-2 and the day of the first cytapheresis) gave similar results to 2% AB serum. None of the 12 patients showed negative effects suggesting the presence of suppressive factors in the sera. Culturing with autologous plasma in clinical trials will lead to a 25% decrease in the total cost of culture and suppress the risk of viral contamination. Excess of granulocytes in the culture (greater than 30%), if the total nuclear cell concentration did not exceed 3 . 10(6) per ml, induced a better proliferation of mononuclear cells without modification of the activation. These results could be due to the liberation of factors by polynuclear cells, or to the loss during elimination of the granulocytes by the Ficoll separation of cells with similar density supporting LAK activity.

Adult↗
PubMed1989

[Immunodeficiency and cancer].

The analysis of cancers associated with immunodeficiencies (either congenital, iatrogenic or acquired) enabled us to define the possible role of these deficiencies in the sequence of events leading to cancer and in particular the emergence of hematopoietic proliferations. Immunodeficiency increases the risk of viral infection, and in severe deficiencies, uncontrolled infections (Epstein-Barr virus) are directly responsible for the appearance of polyclonal proliferations; in moderately severe deficiencies, the hyperstimulation of the immune system by repeated infections increases the number of mutagenic events, but the immortalization of a malignant clone is a late event, which may or may not be linked to a viral infection. On the other hand, some intrinsic congenital or acquired abnormalities of lymphoid cells may be responsible both for immunodeficiency and carcinogenesis (chromosomic fragility). Apart from any immunological reaction, the immune system plays a role in the proliferation and differentiation events in various tissues; and any dysregulation of the latter may indicate the emergence of a cancer.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[Apropos of 100 cases of malaise in infants].

Among 4,411 children hospitalized from May 1985 through April 1987, 100 infants (mean age three months) had exhibited an apparently life-threatening event. Management included careful history taking by interviewing parents, a thorough physical evaluation, routine laboratory tests, and cardiorespiratory monitoring. A variety of further investigations were usually performed to look for gastroesophageal reflux (GER), vagal hyperreflectivity, or sleep-related cardiorespiratory disorders. Leading causes, that often occurred in combination, included GER (66 per cent of cases), and vagal hyperreflectivity (13%). Atypical breath-holding spells, ENT causes, and neurological causes were documented in 8%, 6% and 5% of cases respectively. Medical treatment of the GER proved effective in 90% of cases. Metoclopramide (Primperan, 10 drops/kg/d) was effective in 62% of infants with GER and was well tolerated. Diphemanil methylsulfate (Prantal, 10 mg/kg/d) satisfactorily controlled vagal hyperreflectivity. Monitoring was prescribed in 43% of cases.

Apnea↗