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Biomedical subjects

M Hayat

Publications and source records attributed to M Hayat.

At least 127 records · Page 7Linked to original sources
PubMed1986

The contribution of clinical trials to the treatment of patients with early stages of Hodgkin's disease.

An analysis of the results that have been obtained in several recent controlled clinical trials showed that the inclusion of combination chemotherapy in the initial treatment of Hodgkin's disease significantly improved relapse-free survival but did not improve survival. This is due to the high efficacy of salvage chemotherapy. Paradoxically, the advent of powerful combination chemotherapy makes initial treatment by radiotherapy alone possible in a large proportion of patients with early stages of Hodgkin's disease. Prognostic factors have been identified by a multivariate analysis of the results obtained in the three controlled clinical trials carried out by the EORTC. These factors can help to delineate the subsets of patients who can be treated initially by radiotherapy alone with an acceptable relapse rate and to adjust the size of the radiation fields. The two prominent prognostic factors are: a combination of systemic symptoms and erythrocyte sedimentation rate the number of lymphatic areas involved.

Adult↗
PubMed1985

A multivariate analysis of prognostic factors in early stage Hodgkin's disease.

A multivariate analysis of the prognostic factors was carried out with a Cox model on 1,139 patients with clinical Stage I + II Hodgkin's disease included in three controlled clinical trials. The following indicators had been prospectively registered: age, sex, systemic symptoms, erythrocyte sedimentation rate (ESR), number and sites of involved lymph node areas, histologic type, clinical stage, pattern of presentation, results of staging laparotomy when performed, as well as the date and type of treatment. A linear logistic analysis showed that most of the indicators are interrelated. This emphasizes the necessity of a multivariate analysis in order to assess the independent influence of each of them. The two main prognostic indicators for relapse-free survival are systemic symptoms and/or ESR and number of involved areas. The only significant factor for survival after relapse is age. Sex has a small but significant influence on relapse-free survival. The relative influence of each indicator varies with the type of treatment and these variations may help in understanding the biologic significance of the indicators.

Adult↗
PubMed1985

An alternating chemotherapy and radiotherapy combination for non-Hodgkin's lymphomas of unfavourable histologies: feasibility and preliminary results.

In 1980, on the basis of fundamental and clinical data, a protocol was developed at the Institut Gustave-Roussy, alternating eight monthly courses of chemotherapy (CHVP) and two or three radiotherapy sequences (15 Gy in 6 fractions of 10 days, each), to treat non-Hodgkin's lymphomas of unfavourable histologies, mainly stage II, presenting bulky tumours. Systemic, haematological and digestive tolerances were satisfactory. For 19 previously untreated stage II patients, overall survival and relapse-free survival after 30 months were 85 and 65%, respectively. Three of the relapses were observed in patients who did not receive the alternating schedule in an optimal way; this suggests that these results can be further improved.

Adolescent↗
PubMed1985

Erythropoietic recovery in human after extended field radiotherapy. Ferrokinetic studies of patients treated by radiotherapy followed by autologous bone marrow transplantation and of patients treated by moderate doses (20 Gy) of radiotherapy.

The ability of human irradiated bone marrow to provide suitable environment for migrating stem cells has been studied in four patients. These had received chemotherapy plus doses of 40 Gy to thoracic vertebrae and sternum, followed by autologous bone marrow transplantation. The erythropoietic activity in the non-irradiated areas was increased but it was low in irradiated areas at 3.5 weeks and undetectable at 6 months after autotransplantation. This shows that no nidation of migrating stem cells actively contributed to bone marrow regeneration after 40 Gy and suggests the existence of environmental lesions. No extramedullary erythropoiesis and no bone marrow extension were found in these patients. Four patients who had received doses of 20 Gy to extended bone marrow volume were submitted to ferrokinetic studies from one to 18 years after radiotherapy. In non-irradiated areas the erythropoietic activity was within the normal range. In irradiated areas, it was significantly lower than in the non-irradiated areas and was intermediate between the erythropoietic activity in the sacrum of six healthy control subjects and in the irradiated areas of the four autografted patients. Bone marrow extension was found in these patients. This study suggests that bone marrow recovery after irradiation might not be an all-or-none phenomenon. It would be of interest to better document the dose-effect relationship.

Adult↗
PubMed1984

Prognostic significance of the number of involved areas in the early stages of Hodgkin's disease.

An analysis of 1059 patients with clinical stage (CS) I and II Hodgkin's disease was undertaken to determine the prognostic significance of the number of involved sites. In this group of patients the number of involved lymph node areas was highly correlated with the probability of dissemination of occult disease. In the subgroup of patients with involvement of two lymph node sites (CS II2) approximately 50% demonstrated occult dissemination on the other side of the diaphragm as evidenced by subsequent relapse in the untreated subdiaphragmatic region. However, only 15% to 20% of this group had unsuspected disease in regions other than the spleen or the paraaortic lymph nodes. In CS I and II2 supradiaphragmatic patients, who underwent a staging laparotomy, splenic involvement was a powerful prognostic indicator. When the spleen was not involved, less than 10% of patients had disease elsewhere below the diaphragm, whereas, when the spleen was involved as many as 40% of patients had additional subdiaphragmatic sites involved. In the subgroup with three or more lymph node areas involved (CS II3), the proportion of patients with extension of disease on the other side of the diaphragm, as evidenced by later relapse was also about 50%. But in these patients, unlike the CS II2 patients, analysis of relapse patterns showed that occult disease had already disseminated to the pelvic nodes or to extra nodal sites. Furthermore, splenic involvement was of much less prognostic significance because CS II3 patients who did not demonstrate splenic involvement at staging laparotomy had similar relapse incidence and similar relapse patterns as those with positive spleens.

Adult↗
PubMed1984

Prognostic value of cytologic parameters in acute myelogenous leukemia.

The prognostic value of some current cytologic characteristics was assessed in 174 adult patients with acute myelogenous leukemia (AML) treated according to the AML-5 protocol of the EORTC Leukemia and Hematosarcomas Group. A significantly higher rate of complete remission (CR) was observed in patients with low bone-marrow (BM) cellularity, with BM blasts less than 80%, and with Auer rod positive cells more than 2.5% of the total blast cell population. A leukocyte count of less than 50 X 10(9)/1 in the peripheral blood was also associated with a higher CR rate. No significant difference was found between the various French-American-British (FAB) subtypes, in spite of a trend towards a lower CR rate in patients with an M1, myeloblastic, poorly differentiated, subtype. The leukocyte count and the percentage of Auer rod positive cells were the only significant parameters for duration of survival from the beginning of maintenance treatment. However these features had no prognostic value for the duration of remission. It seems therefore that patients with a higher percentage of Auer-rod-positive cells and lower peripheral leukocyte counts can enter remission more easily, and can also more readily achieve subsequent remissions following relapse. The prognostic value of these routine cytologic features is probably related to their relationship with proliferative activity and tumor burden: the percentage of Auer-rod-positive cells correlates inversely with the leukocyte count, whereas leukocyte count, BM cellularity, and percentage of BM blasts are linked together.

Adolescent↗
PubMed1984

Phase I trial of Idarubicin (4-demethoxydaunorubicin) in adult acute leukemia.

Idarubicin (IDR) is a new analog of Daunorubicin (DNR) selected for clinical trials because of its outstanding activity in experimental leukemias of mice and in several experimental models when compared to DNR and Doxorubicin. This Phase I trial was designed to determine the maximal tolerated dose in adult patients with acute leukemia refractory to prior treatment, using intravenously (I.V.) daily treatments for 5 consecutive days. Eleven patients were entered in this study. The initial dose of IDR was 4 mg/m2/d X 5 I.V. The highest dose given was 8 mg/m2/d X 5 I.V. Dose limiting toxicity were gastrointestinal side effects at the 8 mg/m2/d X 5 level (mucositis-diarrhea). Antileukemic activity has been detected in acute non-lymphoblastic leukemia not pretreated with anthracyclines. For Phase II adult leukemia studies using this schedule, it is recommended that the IDR dose should be 7 mg/m2/d.

Acute Disease↗
PubMed1984

The EORTC treatment of early stages of Hodgkin's disease: the role of radiotherapy.

Since 1964, the European Organisation for Research and Treatment of Cancer has conducted three subsequent clinical trials on clinical Stages (CS) I + II Hodgkin's disease (HD) in which 1059 patients have been entered. The first trial compared regional radiotherapy (RT) with mantle field or inverted Y, versus the same RT followed by a weekly injection of vinblastine for 2 years. The relapse free survival (RFS) and overall survival (S) were higher in patients treated by RT and chemotherapy (CT). This benefit, however, was significant only in patients with a mixed cellularity histologic type. The second trial compared the therapeutic efficacy of splenic irradiation versus splenectomy and found that in both arms, RFS and S were identical. Moreover, it was found that splenic involvement was correlated with an increased incidence of relapse in extranodal sites and in non irradiated lymphatic areas. In this trial, CT was given only to patients with poor histologic types, mixed cellularity or lymphocytic depletion. In the third trial, staging laparotomy was performed only to further delineate a good prognostic group which could be treated by RT alone. In this limited treatment group, there was no difference in RFS and S between mantle field and mantle field + para-aortic RT. In the extensive treatment group, total nodal irradiation (TNI) was compared with RT + MOPP. The RFS was slightly lower in the TNI arm, but there was no significant difference in S. The data of the 3 trials underline the importance of prognostic factors in the choice of optimal treatment and show that their significance depends upon the type of treatment. Multivariate statistical analyses showed that the main prognostic factors, which can help to identify the subsets of patients who can be treated by RT alone, are (1) systemic symptoms and elevated erythrocyte sedimentation rate (ESR), (2) the number of involved lymphatic areas, and (3) staging laparotomy. Extended RT (mantle + para-aortic + spleen treatment) gives satisfactory results in patients without systemic symptoms and/or elevated ESR and one or two involved sites, whereas TNI or combined modality treatment becomes mandatory for patients with 3 or more involved sites or splenic involvement and/or systemic symptoms. With proper adjustment of the irradiated volume, a very large proportion of CS I + II patients can be best treated by RT alone.

Adolescent↗
PubMed1984

Combined radiotherapy-chemotherapy for early stages non-Hodgkin's lymphoma: the 1975-1980 EORTC controlled lymphoma trial.

Patients with stage I and II non-Hodgkin's lymphoma (NHL) are considered to have a relatively good prognosis. For this reason, they are seldom referred to specialized centers and the accrual of such patients in controlled studies is limited. Therefore, significant studies of homogeneously treated patients are difficult to collect and the management of these patients remains controversial. Some patients do very well after treatments with minimal toxicity while others require a much more aggressive approach. The Radiotherapy-Chemotherapy Group of the EORTC carried out its second controlled trial on patients with stage I and II NHL from 1975 to 1980. Its first aim was to assess the prognostic value of histologic classifications independently of treatment. The second aim was to compare two therapeutic options within each stage. In stage I, 124 patients were randomized to receive extended field radiotherapy (RT) either with or without adjuvant cyclophosphamide, vincristine prednisone (CVP) chemotherapy (CT). Relapse-free survival (RFS) was higher in patients who received adjuvant CVP but the total survival rates were not different. The RFS was lower in patients with diffuse than in those with follicular architectural histologies; in the former, RFS was not influenced by adjuvant CVP. Those patients who underwent a staging laparotomy had a higher 5-year total survival (TS) independent of the histologic type. Fifty-six stage II patients were included and extended field was randomized versus total nodal irradiation. Subsequently, adjuvant CVP was given to all patients. Results are good in follicular histologies but the advantage for total nodal irradiation is not significant. In diffuse histologies, results were unsatisfactory in both arms; a new therapeutic strategy was designed in which RT and CT are alternated and has been successfully tested in a pilot study.

Adolescent↗
PubMed1984

Prognostic significance of erythrocyte sedimentation rate in clinical stages I-II of Hodgkin's disease.

A prospective study was undertaken in 1963 on the respective prognostic significances of erythrocyte sedimentation rate (ESR) and presence or absence of systemic symptoms in Hodgkin's disease. Six hundred seventy-six patients with clinical stages I or II were included in this study; 376 from 1963 to 1971 who were included in the H1 trial of the European Organization for Research and Treatment of Cancer (EORTC) and 300 who had been enrolled in the EORTC H2 trial from 1972 to 1976. All relevant data and long-term follow-up are available from 649 patients who were analyzed in this study. Multivariate analysis (Cox model) was carried out to assess the prognostic value of ESR independently of the other prognostic parameters and of the treatment. The results showed that of all the prognostic indicators studied, ESR is the one which has the highest correlation with relapse-free survival; however, initial ESR is not correlated with the probability of death after relapse. The presence or absence of systemic symptoms has less prognostic impact. Despite a close correlation between systemic symptoms and ESR, the two are not redundant and it is useful to combine both.

Blood Sedimentation↗
PubMed1984

[Adjuvant chemotherapy of cancer: definition, prognosis, statistical aspects].

Once the need for adjuvant chemotherapy has been defined with precision, it is important to specify when it may be employed. Two factors determine the decision to use this form of therapy: a) the notion of the presence of malignant tumor, sensitive to chemotherapy (breast, bone ovary), b) knowledge of the elements of prognosis. The probability of relapse is estimated on the basis of these two latter points. Adjuvant chemotherapy is prescribed in cases where the risk of relapse is quite important, attaining 40 to 50 per cent. Its effectiveness can be assessed only with rigorous statistical rules. Randomization only permits a comparison of adjuvant chemotherapy to a control group. Certain errors must be avoided in the interpretation of the results: inaccurate analysis of results such as median comparisons; comparison of the number of deaths or the number of relapses; exclusion of patients after randomization. Only the comparison of the remission duration curves by a test adapted to the form of the curves (Log rank test or Weibull's test) seems justified.

Antineoplastic Agents↗
PubMed1983

Comparative analysis of the immunopharmacological properties of three new nitrosourea analogues: RPCNU, RFCNU and Chlorozotocin.

Three sugar derivatives of chloroethyl nitrosoureas: RPCNU, RFCNU and Chlorozotocin (CLZ) were examined for their effect on the immune system in mice when administered at the minimal antineoplastic therapeutic dose. When the drugs were administered 4 days prior to antigenic stimulation, a potentiation of DTH to oxazolone was observed whereas the antibody response to SRBC was markedly decreased. When injected 24 h after immunization, the nitrosourea analogues did not modify the intensity of DTH reaction and of allograft rejection and only RFCNU depressed the antibody response. The proliferative response of spleen cells to T or B cell mitogens was strongly depressed after in vivo treatment with either of the three analogues. Concomitantly, peritoneal macrophages became strongly cytostatic for tumor cells and also displayed an enhanced chemiluminescence upon phagocytosis. An augmentation of antibody-dependent cellular cytotoxicity of spleen cells was observed only after CLZ administration which also resulted in an increase of NK activity of peritoneal cells but in an inhibition of spleen cell cytotoxicity. This study demonstrates that the nitrosourea analogues act as immunomodulating agents and reinforces their interest as antineoplastic drugs since they can stimulate nonspecific effector mechanisms known to play a role in resistance against tumors.

Animals↗
PubMed1982

[Treatment of acute myeloid leukemia with a protocol combining intensive induction chemotherapy, early consolidation treatment, splenectomy and long-term maintenance chemotherapy. Preliminary study].

Twenty-seven patients aged from 10 to 60 years (mean 34.4 +/- 13 years) in the first perceptible phase of acute myeloid leukemia were subjected to intensive induction chemotherapy consisting of adriamycin (ADM), vincristin (VCR) and cytosine arabinoside (ARA-C). Twenty-four patients (89%) attained complete remission (CR) after 1 to 3 cycles and were then given an early consolidation treatment with one of the previous cycles. This was followed by long-term continuous maintenance chemotherapy with 6-mercaptopurine (6-MP) and methotrexate (MTX) alternatively and 3-monthly reinforcement courses of donaurubicin (DNR) and VCR. Twenty of these 24 patients were splenectomized soon after the consolidation treatment. None of the spleens were enlarged, and histological sections of the spleens, liver biopsies and mesenteric lymph-nodes stained with routine dyes and by the naphthol AS-D chloroacetate esterase method revealed mature granulocytes but no demonstrable leukaemic cells. In the group of splenectomized patients, the probabilities of staying in complete remission at 27 and 44 months were 70 +/- 12.6% and 52 +/- 18.5% respectively, and the probabilities of remaining alive at 32 and 55 months were 79 +/- 11% and 57 +/- 19% respectively. Age over 40 and evidence of extramedullary infiltration at presentation appeared to leave little hope of disease-free survival. The rationale for the present therapeutic study is discussed.

Adolescent↗
PubMed1982

[Fall in the levels of circulating lymphoblasts caused by intravenous administration of the A50 monoclonal antibody in a patient with acute T-cell lymphoblastic leukemia. A step in the demonstration of serotherapy with monoclonal antibodies].

In an 8-year-old boy with acute lymphoblastic leukaemia not previously treated intravenous administration of a single 8 mg dose of a monoclonal antibody that recognizes an epitope restricted to the surface of mature T-cells resulted, within 20 hours, in a fall in circulating lymphoblasts from 200 000 to 70 000. No adverse clinical or biological reaction was detected and no antigenic modulation occurred at lymphoblast surface. This observation constitutes a first step in the complex development of effective serotherapy for malignant diseases, using monoclonal antibodies.

Animals↗