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Biomedical subjects

M Legros

Publications and source records attributed to M Legros.

At least 19 recordsLinked to original sources

New method for stem cell quantification: applications to the management of peripheral blood stem cell transplantation.

A dramatic increase in peripheral blood stem cells (PBSC) is observed after high-dose chemotherapy followed by haematopoietic growth factors. The degree of mobilisation of PBSC is quantified by the level of clonogenic cells detected by CFU assays (CFU-GM or CFU-GEMM) or CD34+ cell determination. Working under the hypothesis that, in peripheral blood, mononuclear cells in DNA synthesis (MCDS) are proliferating stem cells, we decided to detect these cells by flow cytometric measurement of their DNA content. The relations between the number of MCDS and well-known haematopoietic progenitor indicators such as CFU-GM or CD34+ cells were analysed. We studied the kinetics of recruitment of PBSC in cancer patients, treated with rmeHuG-CSF following VP-16 cytoxan chemotherapy, until the first day of leukapheresis. For the 31 patients studied the individual curves of peripheral MCDS and CFU-GM reconstitutions showed identical profiles and a good correlation was noted between the numbers of peripheral MCDS and CFU-GM (r = 0.73). In the leukapheresis product, the predictive value of MCDS was equivalent to CFU-GM for PBSC quantification (r = 0.70). In conclusion, MCDS analysis by flow cytometry provides reliable results and appears to be an alternative to CFU-GM assay or CD34+ cell determination for PBSC quantification.

Adult

Placebo-controlled phase III trial of lenograstim in bone-marrow transplantation.

Haemopoietic growth factors are accepted as accelerating haemopoietic recovery after bone-marrow grafting, yet no large randomised trials have been published that convincingly show benefit. Lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) was given to 315 patients after bone-marrow transplantation in a prospective randomised placebo-controlled multicentre trial. 1 day after bone-marrow infusion, 163 patients received lenograstim 5 micrograms/kg per day by 30-min infusion, and 152 patients received placebo daily for 28 days or until neutrophil recovery. 137 patients had lymphoma, 35 myeloma, 85 acute lymphoblastic leukaemia, and 58 a solid tumour. Patients were stratified by age and by type of bone-marrow transplantation (BMT). Neutrophil recovery to above 10(9)/L for 3 consecutive days was seen earlier in lenograstim-treated patients (16 vs 27 days, p < 0.001). Time to neutrophil recovery above 0.5 x 10(9)/L was reduced (14 vs 20 days, p < 0.001). The difference was significant both in autograft (20 vs 14 days, p < 0.001) and allograft (20 vs 14 days, p < 0.01) patients, in children (20 vs 13 days, p < 0.001), and adults. Lenograstim-treated patients had fewer days of infection, and of antibiotic administration, and also spent less time in hospital. However, clinical and microbiological sepsis was similar in both groups. There was no significant toxicity ascribed to lenograstim. Survival was the same at days 100 and 365. In patients undergoing autologous or allogeneic BMT for neoplastic disease, lenograstim significantly reduced duration of neutropenia and led to earlier hospital discharge.

Adjuvants, Immunologic

The hematopoietic stem cell transplantation in Hodgkin's disease: questions and controversies.

Most patients with Hodgkin's disease (HD) are cured with chemotherapy and/or radiotherapy. However, half of those with advanced stage disease (IIIB, IV) do not respond adequately to treatment or relapse. Salvage therapy used in such cases gives from 10% to 50% complete remission but only 10% long term survival. The results of bone marrow transplantation reported in acute leukemia and non-Hodgkin's lymphoma encouraged some authors to develop this new therapeutic strategy in Hodgkin's disease. In the early 1980's promising results were achieved when refractory and relapsed patients were selected to receive myeloablative therapy followed by bone marrow transplantation. Today, high dose chemotherapy with hematopoietic stem cell transplantation (HSCT) is used more and more often in poor prognosis Hodgkin's disease. After a review of the literature concerning the results of transplantation in Hodgkin's disease, we develop the numerous problems associated with this procedure which remain to be solved such as: the optimal indication, the timing of HSCT, the type of graft, the conditioning regimen, the place of radiotherapy and the optimal use of hematopoietic growth factors. We conclude with future prospects.

Age Factors

[Prognostic value of beta-2-microglobulin in Hodgkin disease in young adults].

From 1977 to 1989, we measured serum beta-2-microglobulin (beta 2-MG) levels from 64 unselected and untreated patients, between 18 to 50-year-old, affected by Hodgkin's disease. Serum beta 2-MG level was measured by radioimmunoassay (Phadebas beta 2 microtest). Then, all patients received a chemotherapy such as MOPP or alternating MOPP/ABVD followed or not by radiotherapy. Elevated serum beta 2-MG level (> 2.4 mg/l) is associated with advanced stage disease (stage III-IV), presence of systemic symptoms and bulky tumor. Nevertheless, a multivariate analysis shows that the serum beta 2-MG level is the most significant prognostic indicator for disease free survival. The prognostic value of serum beta 2-MG is demonstrated for myeloma and non Hodgkin's lymphoma. A few authors have evaluated the prognostic impact of serum beta 2-MG in Hodgkin's disease. This study requires confirmation by multicentric and prospective trial.

Adolescent

[High dose chemotherapy with autologous bone marrow transplantation in ovarian adenocarcinoma].

The present treatment of advanced ovarian adenocarcinoma patients is unsatisfactory, with 5-year survival rates of less than 15%. To obtain better results, one possibility is the use of therapeutic intensification with autologous bone marrow support. In effect, there is a known dose-response relationship in ovarian carcinoma, especially with alkylating agents. To date, a 69% response rate has been achieved with this kind of treatment in 39 patients refractory to standard therapy. However, responses are of short duration, with a median range of 6-7 months. Therapeutic intensification has been used in over 100 patients, as consolidation therapy, following first-line chemotherapy. For these patients, projected 3-year overall survival and disease-free survival rates are 30-50% and 20-40% respectively. These results compare favorably to those of standard therapy. Early deaths are more frequent in refractory patients (18%). Complete hematological recovery usually occurred within 3-4 weeks. Extra-hematological toxicity is related to previous treatment and to cytotoxic drugs used during intensification. These preliminary results, limited to a small series of patients, are sufficiently promising to continue and extend these trials.

Adenocarcinoma

Bone marrow transplantation prolongs survival after relapse in aggressive-lymphoma patients treated with the LNH-84 regimen.

PURPOSE: Of the 737 patients with aggressive lymphoma who were treated with the LNH-84 regimen, 244 with progressive disease after complete remission or partial response were analyzed retrospectively to determine the influence of intensive chemotherapy with bone marrow transplantation (BMT) on survival. PATIENTS AND METHODS: Forty-four patients were treated with salvage chemotherapy, followed by autologous bone marrow transplantation (ABMT) in 40 and allogeneic BMT in four. The other 200 patients were treated with chemotherapy only. RESULTS: Salvage treatment produced an objective response in 57% of the patients; 23% achieved a second complete remission. Median overall survival was longer for patients who were treated with ABMT than for those who were treated with chemotherapy only (12.4 v 6.7 months), as was median freedom from progression (FFP) survival (7.7 v 4 months). In multiparametric analysis, ABMT and normal initial lactic dehydrogenase (LDH) level were the primary parameters associated with longer survival. This is also true when (1) only patients younger than 60 years of age, (2) only patients who responded to salvage regimen, or (3) only patients with both conditions were included in the analysis. Patients who were not transplanted had a 1.69 to 2.26 relative risk of dying from their disease compared with those who were treated with intensive chemotherapy plus ABMT. CONCLUSION: This study produced more evidence of the favorable impact of intensive chemotherapy with bone marrow rescue on survival in lymphoma patients who had relapsed.

Antineoplastic Combined Chemotherapy Protocols

[Adjuvant medical treatment].

Adjuvant medical treatments (chemotherapy or endocrine therapy) are now used in the vast majority of women with breast cancer. They delay recurrences and reduce their number, the increase in survival being particularly marked in limited forms. They also reinforce local treatment and increase the possibility of breast conservation. Their indications can be better determined by precise analysis of prognostic factors, notably tumoral cells.

Adjuvants, Pharmaceutic

Detection of Epstein-Barr viral genomes in lymph nodes of Hodgkin's disease patients.

Previous studies using Southern blot analysis or in situ hybridization have shown that approximately 20% of patients with Hodgkin's disease have Epstein-Barr virus (EBV) in involved tissues. We used the more sensitive polymerase chain reaction (PCR) technique to determine if a higher percentage of EBV could be detected. Of the 16 Hodgkin's disease patients studied, the PCR technique detected EBV in eight (50%). No prognostic significance was associated with the presence of EBV in the eight EBV-positive patients, and the presence of EBV was not associated with B cell monoclonality.

Adolescent

Relation between responses to induction chemotherapy and subsequent radiotherapy in advanced or multicentric squamous cell carcinomas of the head and neck.

Between 1984 and 1986, 85 consecutive patients with Stage III-IV or multi-centric squamous cell carcinoma of the head and neck were given three courses of chemotherapy followed by curative external radiotherapy. Induction chemotherapy consisted of either DDP (100 mg/m2, d 1) + 5 FU (1 g/m2/d, d 1-5, continuous infusion) or DDP (100 mg/m2, d4) + Etoposide (60 mg/m2/d, d 1-5, intravenously). Radiotherapy was delivered 70 Gy over 7 weeks in gross tumor and palpable nodes and 50 Gy over 5 weeks in clinically negative nodal areas. Complete response (CR) rates of both the chemotherapies were 39% for the primary and 20% for the nodes whereas partial response (PR) rates were 22% and 40%, respectively. Six months after completion of radiotherapy, 70% of the primaries and 63% of the nodes achieved complete response. The analysis of responses to chemotherapy on one hand and to subsequent radiotherapy on the other shows that the response to chemotherapy can be regarded as predictive for subsequent radiotherapy (p less than 0.001) except in T1-T2 tumors. In these early stages radiotherapy can be efficacious despite a previous failure of chemotherapy (p less than 0.01).

Adult

[Frontal sinus injuries: apropos of 67 cases].

The authors report their experience in the treatment of frontal sinus fractures, between 1979 and 1987, about 67 cases. 52% of these trauma involve alone, the anterior and/or posterior wall of the frontal sinus, with or without cerebrospinal fluid rhinorrhea. The sinus surgery was composed of cranialization in 20 cases (30%) and open reduction with reconstruction, with or without tube to stent the nasofrontal duct, in 30 cases (48%). Two points appear to them, essential to guide the treatment, osteomeningeal tear and naso-frontal duct injury.

Adolescent

[High doses of alkylating agents and bone marrow autograft in ovarian cancer with poor prognosis: a retrospective analysis of 40 patients treated in France].

Reviewed in this study are 40 patients treated by high-doses of alkylating agents followed by autologous marrow rescue for ovarian cancers. All patients received this therapy after extensive surgery and a median of 6 cycles of CDDP containing regimens (CAP or CHAP). All patients, except 4, who showed evidence of progression, had a second surgical exploration before the high dose chemotherapy. Conditioning regimens consisted of: melphalan at a dosage greater than 140 mg/m2 for all patients; in addition, 2 received Endoxan 120 mg/kg and 1 busulfan 16 mg/kg. Autologous marrow rescue was infused 24 h after the conditioning regimen. Severe, but reversible aplasia and mucositis were the most common toxicities. Three patients died from this procedure, 2 from infection and 1 from secondary leukemia. Twelve out of 15 patients evaluated responded (80%) showing evidence of activity in patients who did not respond to first line chemotherapy. Duration of response was short, especially for patients treated for progressive disease rather than in partial or complete response at the time of high doses chemotherapy. With a median follow up of 23 months (range 8.54) 19 patients survived (15 with non-evolutive disease) leading to a projected survival rate of 39% between 27 months and 5 years. These results are encouraging for poor risk patients who failed to respond to initial chemotherapy. For patients who have small or no residual disease after initial therapy, the place of such intensification should be confirmed prospectively in a larger cohort of patients.

Adenocarcinoma, Mucinous

[Rhino-genioplasty].

The authors explain the great rules of the nose and chin interventions, isolated or combined. They dwell on the value of a strict analysis of the nose and the whole facial structures. These operations called "profiloplasty" are executed on a balanced face, regarding to its skeletal basis.

Chin

[Epithelial cancer of the ovary. Contribution of the experiences of a treatment facility to the current data of prognosis and treatment].

Results obtained by the authors and a review of the literature have made them able to point out recent developments in cases of epithelial cancer of the ovary diagnosed in an advanced stage of the disease. This is the most frequent finding when the diagnosis is made and it is most important in assessing the future prognosis to know how far on the disease has progressed. Cancer of the ovary has long been thought of as a peritoneal disease, but all the same 40% of metastases occur further away and the majority of these are in the pleura or the lung and more rarely in the brain; and all these have been observed. The degree of differentiation is another important element for prognosis. Deciding how differentiated tissue is, is relatively subjective. A scoring protocol is suggested to make the assessment more systematic. The grading can be varied according to the response to treatment. A great majority of authorities believe that reduction of the size of the tumour surgically should be the first procedure but how useful this is has never been proved because there has never been any controlled study. It is possible in most cases to reduce the size of the tumour greatly but often this may need removal of some of the intestines with acceptable morbidity. Chemotherapy with Cisplatin, Cyclophosphamide and in the hands of certain authors, Doxorubicine, has been shown to be helpful in 80% of cases and seems to be the most appropriate treatment.

Carcinoma

[Injuries of the frontal sinus].

The authors report their experience in the treatment of frontal sinus fractures, between 1979 and 1987, about 67 cases. --52% of these trauma involve alone, the anterior and/or posterior wall of the frontal sinus, with or without cerebrospinal fluid rhinorrhea; --the sinus surgery was composed of cranialization in 20 cases (30%) and open reduction with reconstruction, with or without tube to stent the nasofrontal duct, in 30 cases (48%). Two points appear to them, essential to guide the treatment: --osteomeningeal tear, --naso-frontal duct injury.

Adolescent

High dose melphalan and autologous marrow rescue in advanced epithelial ovarian carcinomas: a retrospective analysis of 35 patients treated in France.

We retrospectively evaluated the feasibility and antitumour efficacy of high dose melphalan (HDM) followed by autologous marrow rescue in 35 patients with common epithelial ovarian cancers. All patients initially had advanced disease (FIGO III-IV) and received HDM after extensive surgery and a median of 6 cycles of cis-DDP containing regimens CAP or CHAP. All, except three patients who showed evidence of progression, had a second surgical exploration before high dose chemotherapy. Melphalan was given at a dosage greater than or equal to 140 mg/m2 followed 24 h later by autologous marrow rescue. Severe but reversible aplasia and mucositis were the most common toxicities: three patients died from the procedure, two from infection and one from secondary leukaemia. HDM was effective in 75% of evaluable patients; this was evidence of activity in patients who failed to respond to first line chemotherapy. The duration of response was short, particularly for patients treated with progressive disease at the time of high dose chemotherapy rather than in partial or complete remission. With a median follow-up of 23 months (range 8-54) after high dose chemotherapy, 19 patients are alive (15 with non-progressive disease) with a projected survival of 47% between 2 and 5 years.

Adult