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Biomedical subjects

J M Cosset

Publications and source records attributed to J M Cosset.

At least 127 records · Page 7Linked to original sources
PubMed1991

Bone marrow transplantation in 107 patients with severe aplastic anemia using cyclophosphamide and thoraco-abdominal irradiation for conditioning: long-term follow-up.

Since 1980, 107 consecutive patients (pts) underwent bone marrow transplantation (BMT) for nonconstitutional severe aplastic anemia (SAA) at our institution. All received conditioning with Cytoxan (150 mg/kg) and thoraco-abdominal irradiation (6 Gy) from an HLA-identical sibling donor. Mean age was 19 years (5 to 46 years). Forty-nine pts had less than 0.2 x 10(9)/L PMN and 53 failed to respond to previous immunosuppressive therapy before BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate (22 pts), cyclosporine (52 pts), or both (33 pts). With a median follow-up of 45 months (12 to 120 months), overall actuarial survival was 68% (confidence interval 95%:9.7). Of 16 factors tested, five were shown to adversely influence survival by multivariate analysis: grade greater than or equal to 2 acute GVHD (relative risk [RR]: 5.5), prior immunosuppressive therapy (RR: 3.5), female as donor (RR: 2.4), nonidiopathic SAA (RR: 2), and more than 0.2 x 10(9)/L PMN AA (RR: 2). Because acute GVHD was the most potent factor for survival, we analysed risk factors for acute GVHD. By multivariate analysis, 2 of 14 factors tested were independent: male as recipient (RR: 3) and previous alloimmunization of the donor (RR: 4.3). On long-term follow-up, chronic GVHD was observed in 49 pts of 89 surviving more than 100 days (55%). Multivariate analysis showed that infection before transplant (RR: 1.3) and previous history of acute GVHD (RR: 1.8) were associated with an increased risk of chronic GVHD.

Abdomen↗
PubMed1991

Increased incidence of solid malignant tumors after bone marrow transplantation for severe aplastic anemia.

From May 1980 to December 1989, 107 consecutive patients with non-constitutional severe aplastic anemia underwent bone marrow transplantation at our institution using cyclophosphamide and thoraco-abdominal irradiation as conditioning regimen. During the same period, 40 patients with Fanconi anemia were also grafted after a similar conditioning, giving a total series of 147 patients. With a mean follow-up of 64 months, four male patients developed a solid malignant tumor, a number that leads to an 8-year cumulative incidence rate of 22% (eg, relative risk to general population = 41, P less than .001). These results should be considered as a warning to clinicians who follow these successfully grafted long-term patients.

Aged↗
PubMed1991

Therapeutic implications and sites of relapse predicted by elevated posttherapy erythrocyte sedimentation rate in early stage Hodgkin disease.

An analysis was performed of all 57 early relapses (ER) (within 18 months of therapy initiation) seen in a group of 301 patients treated on three successive European Organization for Research and Treatment of Cancer (EORTC) protocols from 1964 to 1981; to determine whether a posttherapy elevated erythrocyte sedimentation rate (ESR) (greater than or equal to 30 mm) could predict the type of relapse and the effect upon the relapse of different therapies received. Overall most ER occurred in extranodal (EN) (42%) or irradiated transdiaphragmatic nodal (TDN) (40%) sites. Compared to patients with normal posttherapy ESR (n = 12), patients with elevated posttherapy ESR (n = 45) had the same proportions of outfield and late relapses; more frequent multiple sites of ER (38% vs. 25%), increased proportions of early EN relapses (16% vs. 3%), TDN relapses (17% vs. 2%), and other ER (6% vs. 1%). ER were most frequently observed between 1964 and 1971, and "modern" radiotherapy (Rt) decreased ER overall from 27% to 13% and for elevated posttherapy ESR patients from 54% to 25%. When chemotherapy (Ct) was used as either adjuvant or initial therapy, ER were greatly reduced vs. Rt alone [overall (6% vs. 28%) and for patients with elevated posttherapy ESR (10% vs. 39%)]. Stepwise logistic regression showed Ct to be the most important factor "protecting" from EN relapse, but elevated posttherapy ESR was still significant. For early TDN relapse, elevated posttherapy ESR had the highest predictive value for relapse, greater than the types of radiation fields used and chemotherapy. An unexplained elevated posttherapy ESR, regardless of previous therapy, predicts for ER from aggressive HD, frequently in EN and irradiated areas, and warrants further early therapy.

Adult↗
PubMed1991

Application of the LQ model to the interpretation of absorbed dose distribution in the daily practice of radiotherapy.

In 1991, the vast majority of radiotherapy centers are implemented with computer treatment planning systems (TPS), and it has become routine practice to compute full absorbed dose distribution (ADD) in almost all treatment situations. Usually the target is covered by the 100% isodose and the surrounding normal tissues receive a lesser dose than the tumor. It implies, that, as the dose per fraction of, say, 2 Gy is prescribed at the 100%, normal tissues receive a daily dose different than 2 Gy. The absorbed doses delivered at different organs have therefore not the same biological effectiveness and must be corrected according to the actual dose per fraction for a proper interpretation of the treatment planning. This is of great importance since most of the "tolerance levels" used in the practice have been determined for doses per fraction around 1.8-2 Gy. The linear-quadratic (LQ) model provides a simple method for establishing biological equivalencies and has been used throughout this article to establish the difference between the absorbed dose computed by the TPS and its biological equivalent. It is shown that normal tissues receiving less than 100% of the daily dose are relatively more protected than suggested by the ADD, and, inversely, that normal structures overdosed and thus receiving more than the 100% daily dose are relatively more at risk for complications than suggested from the ADD.

Bronchial Neoplasms↗
PubMed1991

Alternating chemotherapy and radiotherapy combination for bulky stage I and II intermediate and high grade non-Hodgkin lymphoma: an update.

In 1980, based on experimental and clinical data, a protocol was developed at the Institut Gustave-Roussy (IGR), alternating eight monthly courses of chemotherapy (CHVP) and two, then three, radiotherapy sequences (15 Gy in 6 fractions and 10 days to the initially involved areas), for early stage unfavourable histology non-Hodgkin lymphomas (NHL). The results are updated for 55 selected patients presenting with bulky stage I and II NHL, intermediate and high grade according to the Working Formulation. Five-year overall survival rate was 69% and freedom from progression was 68%. Early haematologic and digestive tolerance was satisfactory, probably because a 10-15-day interval was respected between chemotherapy and radiotherapy and vice versa. No late toxicity was detected in 39 patients who presented with head and neck localizations; xerostomia was found to be only mild and transient. All patients given mediastinal irradiation experienced radiological mediastinitis, but functional impairment was usually moderate. One of the 4 patients who received 3 x 15 Gy radiotherapy courses to part of the abdomen, died of small bowel obstruction and perforation. The study demonstrated the feasibility of an alternated schedule of chemotherapy and radiotherapy, with satisfactory results in terms of long-term survival. However, the few late complications which were detected after irradiation of the abdomen or of the thorax led to an alteration of the initial scheme when these volumes are to be treated.

Adolescent↗
PubMed1991

Estimation of clonogenic cell fraction in primary cultures derived from human squamous cell carcinomas.

Tumor clonogenic cell content is believed to play an important role in the outcome of radiotherapy. However, there is no proven method to assess the number of clonogens in human tumors accurately. All currently available assays employ in vitro plating efficiency or in vivo TD50 (the average number of cells needed to induce tumors in 50% of injected mice) to estimate the tumor clonogenic ability. In this study, a monolayer mass primary culture system was used to estimate the clonogenic cell fraction in human tumors. For this purpose, 25 growth curves were performed for 25 tumor specimens derived from 21 head and neck and 4 cervical squamous cell carcinomas. The exponential portion of each growth curve was extrapolated through the ordinate (day 0) to estimate the clonogenic cell fraction; this method is only an estimate because it assumes no lag phase before exponential growth of clonogenic cells. The mean clonogenic cell fraction, expressed as clonogens/tumor cells inoculated, was relatively low (mean: 0.71%, range: 0.11-9.28), and the variation was wide (coefficient of variation = 148%). On the other hand, the doubling time of the growing population was 1.46 days and exhibited a very narrow range (0.98-2.24, coefficient of variation = 24%). The mean and range of clonogenic cell fraction were found to be in agreement with published values of soft agar colony forming efficiencies in both murine and human tumors. However, further investigation is necessary to determine how accurately this method measures the relative clonogenic cell content in human tumors. Clinical correlations between clonogenic cell fraction values and the response to radiotherapy are still too early to determine.

Carcinoma, Squamous Cell↗
PubMed1991

Pericarditis and myocardial infarctions after Hodgkin's disease therapy.

From 1971 to 1984, 499 patients with all stages of Hodgkin's disease received mediastinal irradiation at the Institut Gustave-Roussy by 25 MV photons from a linear accelerator. Thirty-five pericarditis (10-year cumulative incidence rate of 9.5%) and 13 myocardial infarctions (MI) (10-year cumulative incidence rate of 3.9%) were observed. In contrast, no cases were diagnosed in a parallel series of 138 Hodgkin's disease patients treated without mediastinal irradiation during the same period of time (p less than 0.005 for pericarditis, p less than 0.05 for MI). By multivariate analysis, the role of total radiation dose given to the mediastinum and that of fraction size were evaluated, adjusting for age, sex, mediastinal involvement, and type of chemotherapy. The pericarditis risk was significantly increased with total dose greater than or equal to 41 Gy (relative risk (RR) = 3.25, p = 0.006) and with dose per fraction greater than or equal to 3.0 Gy (RR = 2.0, p = 0.06). The myocardial infarction risk was not found to be related to total dose nor to fraction size in this series, possibly because of the small number of events.

France↗
PubMed1991

[Immediate hematologic tolerance of extended irradiations after chemotherapy. Apropos of 78 cases of Hodgkin's disease stage III and IV without marrow involvement treated at the Gustave-Roussy Institute].

Early hematotoxicity following 4 to 8 courses of polychemotherapy has been analysed in 78 patients (mean age 32.5 years) treated for advanced stage Hodgkin's disease (53 stages III, 25 stages IV). Toxicity occurred in a third of the patients, and led to interrupt the treatment in one case out of 7, definitively in half of them. The thrombocyte lineage appeared the most sensitive to irradiation. Toxicity was proportional to the target volume (42% of upper and infra-diaphragmatic field versus 11.5% of one sided irradiation, P = 0.01). Toxicity was more frequent after infra-diaphragmatic irradiation (32% of para-aortic field, 43.75% of inversed Y field) than after mantle field (12.3%, P = 0.01). Tolerance to extended field irradiations seemed better in young patients. Sex, stage, type of chemotherapy did not influence toxicity in our series. Abnormalities of the blood count before irradiation was predictive of toxicity. While expecting development of megakaryocytic growth factors of autologous bone marrow transplantation, we suggest: 1) to achieve total lymphoïd irradiation in three periods (mantle field then lombo-aortic field-/+ spleen, then iliac and inguinal fields); 2) to wait, if possible, until normalization of the hemogram before starting the irradiation.

Adolescent↗
PubMed1991

[Primary lymphoma of the central nervous system. Review of recent literature data].

Primary CNS lymphoma is a rare entity. In the last few years, increasing numbers of reports have focused on the clinical, radiological and biological aspects of this tumor. The problem of the therapy of this particular localisation of lymphoma remains mostly unsolved. Radiotherapy still remains the standard approach. However, recent trials combining chemo and radiotherapy have shed promising light on a dark prognosis. These aspects are reviewed based on recent reports in the literature.

Brain Neoplasms↗
PubMed1991

Blood cell kinetics after a 385 cGy total body irradiation given to a CML patient for bone marrow transplantation.

Fractionated total body irradiation was given to a patient with chronic myeloid leukemia as part of a conditioning regimen for bone marrow transplantation. The radiation treatment was discontinued after the third fraction (total dose: 385 cGy) and no bone marrow graft was given because of the patient's refusal. Peripheral blood lymphocyte levels were monitored for 3 months and lymphocyte subsets up to 50 days post-irradiation. Lymphocyte numbers reached the nadir 48 h after the last fraction and lymphopenia was still present 3 months later. All lymphocyte subsets (T, B, CD4 and CD8 cells) showed a similar decrease except for natural killer cells which exhibited a larger decline. The regenerative capacity of T cells, CD4 subset and natural killer cells was less than that of B cells and CD8 lymphocyte subsets.

Adult↗