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Biomedical subjects

M Henry-Amar

Publications and source records attributed to M Henry-Amar.

At least 91 records · Page 5Linked to original sources

High-dose beclomethasone: oral steroid-sparing effect in severe asthmatic patients.

One hundred and twenty four patients with severe asthma requiring maintenance treatment with oral corticosteroids were included in a multicentre, double-blind, randomized study comparing the effects of inhaled beclomethasone dipropionate (BDP) (250 micrograms.puff-1), beginning with 1,000 micrograms daily, vs placebo (P). Pulmonary function was assessed and dosage of prednisone and BDP (or P) were adjusted every 15 days according to a clinical score. Our results showed, after 3 months: 1) A greater drop-out rate in the P group than in the BDP group (36 vs 6%, respectively, p less than 0.01); 2) A total weaning from prednisone in 76% of patients in the BDP group (mean BDP dosage = 1,270 +/- 340 micrograms.day-1, mean +/- SD), vs 34% in the P group (p less than 0.001). The mean daily dosage of prednisone was reduced from 17 +/- 7.5 mg to 3.1 +/- 7.4 mg in the BDP group vs 15.6 +/- 7.7 mg to 9.1 +/- 9.4 mg in the P group (p less than 0.001) without any relationship between the steroid-sparing effect and the initial dosage of prednisone; 3) Mean change in forced expiratory volume in one second (FEV1) was +7 +/- 21% from the initial value in the BDP group vs -6 +/- 20% in the P group; p less than 0.01. Thus, in patients with severe asthma requiring oral corticosteroids, high-dose BDP has an important oral steroid-sparing effect not related to the initial dosage of oral steroids and allows a better control of airway obstruction than oral corticosteroids alone.

Administration, Inhalation↗

Leukemia following Hodgkin's disease.

To investigate the effect of different treatments for Hodgkin's disease on the risk of leukemia, we used an international collaborative group of cancer registries and hospitals to perform a case-control study of 163 cases of leukemia following treatment for Hodgkin's disease. For each case patient with leukemia, three matched controls were chosen who had been treated for Hodgkin's disease but in whom leukemia did not develop. The use of chemotherapy alone to treat Hodgkin's disease was associated with a relative risk of leukemia of 9.0 (95 percent confidence interval, 4.1 to 20) as compared with the use of radiotherapy alone. Patients treated with both had a relative risk of 7.7 (95 percent confidence interval, 3.9 to 15). After treatment with more than six cycles of combinations including procarbazine and mechlorethamine, the risk of leukemia was 14-fold higher than after radiotherapy alone. The use of radiotherapy in combination with chemotherapy did not increase the risk of leukemia above that produced by the use of chemotherapy alone, but there was a dose-related increase in the risk of leukemia in patients who received radiotherapy alone. The peak in the risk of leukemia came about five years after chemotherapy began, and a large excess persisted for at least eight years after it ended. After adjusting for drug regimen, we found that patients who had undergone splenectomy had at least double the risk of leukemia of patients who had not, and an advanced stage of Hodgkin's disease carried a somewhat higher risk of leukemia than Stage I disease. We conclude that chemotherapy for Hodgkin's disease greatly increases the risk of leukemia and that this increased risk appears to be dose-related and unaffected by concomitant radiotherapy. In addition, the risk is greater for patients with more advanced stages of Hodgkin's disease and for those who undergo splenectomy.

Antineoplastic Agents↗

Causes of death after therapy for early stage Hodgkin's disease entered on EORTC protocols. EORTC Lymphoma Cooperative Group.

The risk of dying from different causes after Hodgkin's disease (HD) therapy has been quantified from a series of 1,449 patients with early stages included in four successive clinical trials conducted by the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Cooperative Group since 1963. Overall, 240 patients died and the 15-year survival rate was 69% whereas the expected rate was 95%. The standardized mortality ratio (SMR) technique was used to quantify excess deaths as a function of time since first therapy. At each interval, SMR was significantly increased, giving: 0-3 year, 8.86 (p less than 0.001); 4-6 year, 9.25 (p less than 0.001); 7-9 year, 7.08 (p less than 0.001); 10-12 year, 9.53 (p less than 0.001); 13-15 year, 4.37 (p less than 0.01); and 16+ years, 3.80 (p less than 0.05). While the proportion of deaths as a consequence of HD progression, treatment side-effect, and intercurrent disease decreased with time, that of second cancer and cardiac failure peaked during the 10-12 year post-treatment interval. After 15 years of follow-up, the risk of dying from causes other than HD continued to increase. These findings indicate that although probably cured from HD, patients are at higher risk for death than expected, a risk that might be a consequence of therapy.

Adult↗

Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly.

We conducted a randomized multicenter trial comparing low-dose cytarabine (LD ARA-C) (20 mg/m2 for 21 days) with an intensive chemotherapy (rubidazone [a daunorubicin-derived agent], 100 mg/m2 for 4 days, ARA-C 200 mg/m2 for 7 days) in 87 patients over 65 years of age with de novo acute nonlymphocytic leukemia (ANLL). Forty-one patients received LD ARA-C and 46 received intensive chemotherapy. The number of complete remissions (CRs) but also of early deaths was higher in the intensive chemotherapy group, while partial remissions (PRs) and failures were more frequent in the LD ARA-C group (P less than .001). Infectious complications during induction treatment were more numerous and more severe in the intensive chemotherapy group (P less than .01). Patients treated with LD ARA-C required fewer RBC transfusions (P less than .02), fewer platelet transfusions (P less than .01), and had a shorter hospital stay for induction treatment (P less than .01). Overall survival and CR duration were not significantly different in either group. In the LD ARA-C group, the survival of patients with PR and those of patients in CRs was identical. We conclude that in a selected group of elderly patients with de novo ANLL a higher number of CRs may be obtained with intensive chemotherapy, but that with LD ARA-C, the number of early deaths is lower, and long-lasting PRs are obtained, resulting in a similar overall survival.

Aged↗

[Primitive digestive localizations of malignant non-Hodgkin's lymphoma. Prognostic factors of locally advanced disease: stage II. Report of 67 cases].

Sixty-seven patients with non-Hodgkin's lymphoma of the digestive tract with locally advanced disease (stage II) were analyzed to determine the main factors influencing survival. There were 19 patients with stage II E1 and 48 with stage II E2 disease (Musshoff classification). According to the Kiel classification, 46 percent were low grade, 46 percent were high grade, and 8 percent were unclassified. The principal sites involved included the stomach: 11 cases, small intestine: 21 cases, colon: 12 cases, and mesentery: 11 cases. Lymphoma was unique in 45 cases (67 percent). Treatment consisted of laparotomy in 61 of 67 cases: partial resection was achieved in 21 cases, complete resection in 27 cases, and exploration only in 13 cases. Chemotherapy, according to histopathological subtypes, was employed in 90 percent of cases. Radiation therapy was applied in 25 patients (37 percent), essentially when there was residual disease after surgery (17 patients). Therapeutic indications were dependent on histological subtype, extension, and the therapy regimen in use at the time of treatment. Five patients were treated by surgery only, 2 by surgery and radiation therapy, 37 by surgery followed by chemotherapy, and 23 by all three treatment modalities. Overall survival was 62 percent at 5 years. Univariate analysis showed that 5-year survival rates were not influenced by sex, age, histopathological subtype (low grade: 69 percent; high grade: 59 percent; NS) or local extension (stage II E1: 76 percent vs stage II E2: 59 percent; NS). In contrast, complete surgical excision (p = 0.06) and radiation therapy in case of local residual disease (p = 0.02) seemed to improve survival. The main prognostic factor was the achievement of a complete therapeutic response (CR) (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Prognostic factors in primary gastrointestinal non-Hodgkin's lymphoma. A multivariate analysis, report of 106 cases, and review of the literature.

The authors have reviewed 106 cases of primary gastrointestinal non-Hodgkin's lymphoma (GI-NHL) treated at the Institut Gustave-Roussy (IGR), France, between 1975 and 1986. The occurrence was 55 in the stomach, 26 in the small intestine, ten ileocecal, seven in the large intestine, and eight patients had multiple involvement. Patients were clinically staged according to the Ann Arbor staging system using the modification of Musshoff for Stage IIE. All histologic material of the 106 patients were reviewed and graded according to the Working Formulation (WF) and the Kiel classifications. Most patients received combination chemotherapy as part or all of their primary treatment program (95 patients, 90%). Seventy five patients (71%) had a multimodality treatment. The overall 5-year survival rate was 60%. Sixteen variables were tested by univariate analyses for prognostic influence on survival. Of these, only clinical stage (P less than 0.001), the achievement of initial complete remission (CR) (P less than 0.001), erythrocyte sedimentation rate (ESR) (P = 0.01), mesenteric involvement (P = 0.03), and serosal infiltration (P = 0.05) were significant prognostic factors. Important variables were tested by a multivariate analysis using the Cox model taking into account different treatment modalities. Only three variables entered the regression analysis at a significant level: clinical stage (P = 0.02), surgical resection (P = 0.03), and histologic grade (Kiel) (P = 0.04). When the achievement of initial CR was introduced into the model, it was the most significant variable (P less than 0.001) whereas all other variables became nonsignificant except for the histologic grade (Kiel) (P = 0.004). Based on results of the multivariate analyses we propose two prognostic classifications of patients: one at the initial evaluation depending on clinical stage, surgical resectability, and histologic grade (Kiel); the other at the end of primary treatment depending on the achievement or not of CR and the histologic grade.

Adolescent↗

Risk of secondary acute leukemia and preleukemia after Hodgkin's disease: the Institut Gustave-Roussy experience.

From 1960 to 1984, 871 patients were treated for Hodgkin's disease at the Institut Gustave-Roussy. Twenty-six percent of the cohort were treated with radiotherapy (RT) alone, 6% with chemotherapy (CT) alone, and 68% with a combination of RT and CT, either at first line or for salvage treatment. MOPP chemotherapy was given to 42% of the patients. Overall, 19 secondary acute leukemias or preleukemias were observed, 3 of them after extended RT alone, the other 16 after a combination of RT and MOPP. Among the alkylating agents used, only nitrogen mustard (mechloretamine) was shown in a multivariate analysis to be significantly associated (P less than 0.001) with an increased risk of secondary leukemia. A dose response was observed, with the risk relative to general population incidence rates being 45 in patients having been treated with 1-59 mg (total dose) of nitrogen mustard, 211 in those treated with 60-119 mg, and 636 in those treated with greater than or equal to 120 mg. No other factors were found to be associated with leukemia risk. The 10-year cumulative incidence of leukemia was zero in patients treated with limited RT alone, 2.4% in those treated with extended RT alone, 0% in those treated with a combination of RT and CT without nitrogen mustard, and 12.4% in those treated with RT + nitrogen mustard. Whether other alkylating agents give a similar result remains to be determined; these data suggest that the use of nitrogen mustard at a higher total dose than 60 mg is questionable in the treatment of Hodgkin's disease.

Adult↗

Relationship of histological subtypes to prognosis in early stage Hodgkin's disease: a review of 312 cases in a controlled clinical trial. The Groupe Pierre et Marie Curie.

To assess the prognostic significance of a newer histologic classification of Hodgkin's disease (HD), microscope slides from the time of diagnosis of 312 clinical stage IA or B, IIA or B and IIIA patients were reviewed in 1987, 6-10 years after their participation in a radiochemotherapeutic trial (1976-1982). Overall, the diagnostic reproducibility of the Rye classification by the same pathologist was confirmed. However, a new analysis showed an improvement in the differential diagnosis between HD and non-Hodgkin's lymphomas (NHL) by the identification of 24 NHL (8%) amongst the patients originally diagnosed as HD. Most of the NHL identified on review had been classified originally as mixed cellularity. On review, none of the new histological subtypes of HD was significant for prognosis of relapse-free survival or overall survival. Only identification of NHL was shown to have an independent prognostic value on relapse rate (P = 0.012) and on overall survival (P = 0.10). It is concluded that diagnosis of HD by itself remains, in 1988, the sole histologic factor influencing the prognosis of these patients.

Adolescent↗

High doses of inhaled corticosteroids in unstable chronic asthma. A multicenter, double-blind, placebo-controlled study.

In a multicenter, randomized, double-blind study, inhaled beclomethasone dipropionate (BDP) 1,500 micrograms/day was compared to placebo in 43 chronic asthmatic patients uncontrolled by inhaled salbutamol and oral theophylline. During the prestudy period, a test of maximal steroid reversibility with oral prednisolone 0.5 mg/kg/day for 14 days was performed. The therapeutic response was measured over an 8-wk period as the ability to maintain the clinical improvement and the optimal pulmonary function induced by prednisolone. During the study, severe asthma exacerbation occurred in one (5%) of the 21 patients who received BDP and in 15 (78%) of the 22 patients who received placebo (p less than 0.001). In patients who received BDP, FEV1 and peak expiratory flow (PEF) remained above the optimal postprednisolone value, with a trend to improvement during the 8-wk study period. In patients who received placebo, FEV1 and PEF decreased and remained below the optimal value. We conclude that, in chronic asthma, inhaled BDP 1,500 micrograms/day maintains the optimal pulmonary function in addition to the clinical benefit induced by a short course of oral corticosteroids.

Administration, Inhalation↗

Toward comprehensive management tailored to prognostic factors of patients with clinical stages I and II in Hodgkin's disease. The EORTC Lymphoma Group controlled clinical trials: 1964-1987.

From 1964 to 1987, the EORTC Lymphoma Group conducted four consecutive controlled clinical trials on clinical stages I and II Hodgkin's disease in which 1,579 patients were entered. From the onset the main aim of these trials was to identify the subsets of patients who could be treated safely by regional radiotherapy (RT). Therefore, several prognostic indicators were prospectively registered and progressively used in the trial protocols for the delineation of the favorable and unfavorable subgroups as soon as they were recognized of high predictive value. In the H2 trial (1972 to 1976), the histologic subtype was the only variable taken into account for the therapeutic strategy and the staging laparotomy findings were found to be of prognostic value only in patients with favorable prognostic indicators. In the H5 trial (1977 to 1982), patients were subdivided into two subgroups according to six prognostic indicators. Patients with favorable features were submitted to a staging laparotomy (lap); lap negative patients were randomized between mantle field RT and mantle field plus paraaortic RT. Disease free survival (DFS) and total survival (S) were similar in the two arms. Among patients with unfavorable features, DFS and S were significantly higher in the arm treated by combination of mechlorethamine, vincristine, procarbazine, prednisone (MOPP) chemotherapy (CT) and RT than in the arm treated by total nodal irradiation. Nevertheless, in patients below the age of 40, the overall survival rates were equivalent in the two arms. In the H6 trial, the delineation of the favorable subgroup was based on (a) absence of systemic symptoms and elevated ESR, (b) no more than one or two lymph node areas involved. The aim of the study was to assess the impact on survival of a therapeutic strategy including staging laparotomy. At a 4-year follow-up, no difference in survival was evidenced. In patients with unfavorable prognostic indicators, 3 MOPP-RT-3 MOPP were compared with 3 ABVD-RT-3 ABVD. From H1 to H5 trials, the proportion of patients having received CT during the course of the disease gradually decreased; the data suggest that a further reduction in the proportion of patients aggressively treated is conceptually possible. On the basis of the prognostic factors identified, one can delineate three subsets of patients and modulate toxic cost of the initial treatment according to the characteristics of these subsets. In the most favorable subgroup, RT alone produces high survival and CT is not justified.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Significance of inhibitors of conversion enzymes in elderly subjects. The example of perindopril].

The effectiveness and safety of perindopril in elderly hypertensive patients has clearly been demonstrated. In a randomized, double-blind drug versus placebo study involving 34 such patients of mean age 84 years, we observed a 10 p. 100 fall in systolic arterial pressure (p less than 0.01) and a 9 p. 100 fall in diastolic arterial pressure (p less than 0.01) in the perindopril group. The corresponding figures in the placebo group were 5 p. 100 and 4 p. 100 respectively, the difference between the two groups not being significant. The drug was well tolerated, both clinically and biochemically. However, a significant (p less than 0.01) increase in blood potassium level (albeit within normal limits) was observed in the treated group. An open trial conducted in 91 patients (mean age 79.1 years) followed up for 6 years confirmed the acceptability of the drug despite a transient decrease of creatinine clearance recorded in one patient. The effectiveness of perindopril, evaluated less unquestionably in this open trial, was excellent, the hypertension being controlled at the end of treatment in 92.5 p. 100 of the patients. In a trial performed on healthy volunteers, Reid found that perindopril had a greater effect of arterial pressure in elderly subjects, probably due in part to their high blood pressure and to an earlier and more prolonged inhibition of the angiotensin-converting enzyme (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Value of angiotensin converting enzyme inhibitors in the elderly: the example of perindopril.

The efficacy and safety of perindopril in hypertension (HT) in the elderly have now been clearly demonstrated. In a randomized, double-blind placebo-controlled study conducted in 34 patients with a mean age of 84 years, we observed a significant reduction in systolic blood pressure (SBP) by 10% (p less than 0.001) and in diastolic blood pressure (DBP) by 9% (p less than 0.01) in the perindopril group. In the placebo group, the reduction observed was 5% and 4% respectively, although the difference between the two groups was not significant. The clinical and laboratory safety was satisfactory. However, in the treated group, there was a significant increase in serum potassium (p less than 0.01), which nevertheless remained within normal limits. An open study conducted in 91 patients with a mean age of 79.1 years, followed over a period of 6 months, confirmed the very good acceptability of the drug, despite the transient reduction in creatinine clearance observed in one female patient. The efficacy, evaluated less reliably in an open study, appeared to be excellent as 92.5% of patients were controlled by the end of treatment. In a study in healthy subjects, Reid observed a more intense effect on blood pressure (BP) in elderly subjects, which could be partly explained by a higher blood pressure level and by earlier and more prolonged converting enzyme inhibition (not significant). The practical value of this angiotensin converting enzyme (ACE) inhibitor, related to its efficacy and safety, is reinforced by a theoretical value: its action on arterial compliance, its beneficial effect on cardiac function, its potential action on the renin-angiotensin system of the brain, the structural modifications induced in the arterial wall open extremely stimulating prospects in the field of aging.

Aged↗

Late radiation injuries of the gastrointestinal tract in the H2 and H5 EORTC Hodgkin's disease trials: emphasis on the role of exploratory laparotomy and fractionation.

Out of 516 patients who entered in the two successive EORTC trials H2 and H5 for supra-diaphragmatic stages I and II Hodgkin's disease (HD), and who received an infra-diaphragmatic irradiation, 36 (7%) developed late radiation injuries of the gastrointestinal tract (GIT). Twenty-five patients presented with ulcers (stomach or duodenum), 2 with severe gastritis, 6 with small bowel obstruction or perforation and 3 patients had both an ulcer and bowel obstruction. A previous laparotomy played an important role. While the complication rate was 2.7% without any previous abdominal surgery, it was 11.5% after laparotomy (p less than 0.001). Fractionation was also found to be of importance in the occurrence of complications: three different weekly schedules were used -5 x 2 Gy, 4 x 2.5 Gy and 3 x 3.3 Gy; the GIT complication rates were 4, 9 and 22%, respectively (p less than 0.001). When combining laparotomy and fractionation, we found that the patients who were treated using 5 weekly fractions of 2 Gy without any prior laparotomy had a very low rate of late digestive complications (1%), whereas the patients who received 3 weekly fractions of 3.3 Gy after laparotomy presented a 39% complication rate. The other subgroups of patients were at an intermediate risk (from 5 to 13%) of late digestive injuries. Since most patients received 40 Gy with only very small variations, the influence of the radiation dose could not be investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

Lymphoblastic lymphoma in adults: a clinicopathological study of 34 cases treated at the Institut Gustave-Roussy.

We report a series of 34 adult patients with lymphoblastic lymphoma treated at our Institute between 1977 and 1986. At presentation, mediastinal involvement was seen in 76%, extranodal involvement (not including bone marrow) in 20%, stage IV in 53% and circulating blasts in 15%. In the 15 cases where immunological studies were performed, 12 proved to be of T type and the other three lacked both T and B markers. Chemotherapy with acute lymphocytic leukemia (ALL) protocols was given to 58% and lymphoma protocols to the other patients, with CNS prophylaxis given to a total of 28 patients. Although complete remission (CR) was observed overall in 74% of patients, 5 year survival was only 22% (42% in stages I-II and 8% stages III-IV) with improved results seen with recent aggressive anti-leukemic protocols. Five relapsed patients entered second CR and two were still in CR at this time. CNS relapse occurred in a total of eight patients (three without prophylaxis), and was isolated in two of six patients who achieved CR (despite CNS prophylaxis). In an analysis of prognostic factors, only the attainment of a CR was statistically significant (P less than 0.001). Thus we are unable to confirm other studies which demonstrated prognostic variations in this disease and believe that all such patients should receive aggressive chemotherapy with substantial CNS prophylaxis similar to those currently used for ALL.

Adolescent↗