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Biomedical subjects

M Hayat

Publications and source records attributed to M Hayat.

At least 91 records · Page 5Linked to original sources
PubMed1989

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↗
PubMed1989

Single dose versus hyperfractionated total body irradiation before allogeneic bone marrow transplantation: a non-randomized comparative study of 54 patients at the Institut Gustave-Roussy.

At the Institut Gustave-Roussy (IGR), from January 1982 to December 1986, 54 patients received total body irradiation (TBI) as a part of the conditioning regimen before allogeneic bone marrow transplantation. The patients were non-randomly assigned to either single dose TBI (STBI) (31 patients receiving 10 Gy at a 4.5 cGy/min dose rate, 8 Gy to the lungs) or to a hyperfractionated scheme (HTBI) (23 patients receiving 13.2 Gy in 11 fractions, 3 fractions per day, 9 Gy to the lungs). Relapse rate and overall survival were not significantly different in the two STBI and HTBI groups, in spite of a larger number of 2nd and 3rd remission patients in the HTBI subset. The incidence of interstitial pneumonitis (IP) was significantly reduced in the HTBI group (13%, versus 45% after STBI, p = 0.02). Lethality by IP was also lower after HTBI (4%, versus 26% after STBI, p = 0.08). There was no case of veno-occlusive disease of the liver in the HTBI group, whereas three cases were observed after STBI. Based on these results, the IGR activated, in January 1987, a randomized trial comparing the single dose 10 Gy TBI (8 Gy to the lung) to a new hyperfractionated schedule (11 fractions of 1.35 Gy, 3 fractions per day, 9 Gy to the lungs).

Adult↗
PubMed1989

Phase II trial of idarubicin (4-demethoxydaunorubicin) in advanced breast cancer. The Clinical Screening Group of the European Organization for Research and Treatment of Cancer.

A phase II trial of idarubicin (IDR-4 demethoxydaunorubicin) was carried out in patients with advanced breast cancer. A dose of 45 mg/m2 was given orally once every 3 weeks. A total of 66 eligible patients were entered into the trial, 56 of whom were evaluable for response (65 were evaluable for toxicity at least). Therapeutic activity was demonstrated with an overall objective response rate of 21% (95% CI: 11-32%). When used as a first-line treatment, the response rate was 33% (95% CI: 9-57%) but this dropped to 17% when the treatment was administered after chemotherapy. Nausea-vomiting was the most frequent and severe non-hematological toxicity observed (WHO grade 3-4: 29%). Loss of hair was noticed in 48% of the patients but only 4% suffered from complete alopecia. Moderate myelotoxicity was reported but no cardiac dysfunction was noticed. IDR could be very advantageous as compared to other anthracyclines, due to its simplicity of administration associated with the lack of risk of extravasation or chemical phlebitis and also the possibility of it being able to reduce cardiotoxicity. Even if the equiefficacy of IDR and DXR has not, as yet, been clearly demonstrated, IDR should be chosen with preference to DXR when administration is not suitable.

Adult↗
PubMed1989

Treatment of acute myelogenous leukemia. An EBMT-EORTC retrospective analysis of chemotherapy versus allogeneic or autologous bone marrow transplantation.

In a retrospective analysis, patients with acute myelogenous leukemia (AML), treated in first complete remission (CR) with chemotherapy or with allogeneic or autologous bone marrow transplantation were compared with respect to their leukemia-free survival from CR. Two hundred and thirty-six patients treated with chemotherapy according to the EORTC AML-5 and AML-6 trials were included. The data of the transplanted patients were taken from two EBMT registries; 453 with an allogeneic and 182 with an autologous BMT. The very different sources of the data (trials and registries) forced us to be cautious in our conclusions. However, for the patient cohorts analyzed in the present study, BMT patients tended to have a better leukemia-free survival than chemotherapy patients. This was especially the case for the allogeneic BMT after 6 months of transplant.

Adolescent↗
PubMed1989

Failure of a CD18/anti-LFA1 monoclonal antibody infusion to prevent graft rejection in leukemic patients receiving T-depleted allogeneic bone marrow transplantation.

CD18 antibodies react with the common beta chain of the human leukocyte function antigen (LFA1)* and thus block the functions mediated by the three identified molecules in humans. A murine CD18 monoclonal antibody was infused in 8 leukemic patients receiving allogeneic T-depleted bone marrow transplantation in order to prevent graft rejection. This was part of the conditioning, including total-body irradiation and high-dose chemotherapy, given to all patients. To prevent graft-versus-host disease the donor bone marrow T cells were depleted using complement-mediated cytolysis or a ricin A conjugate immunotoxin, and cyclosporine or methotrexate were given posttransplant. A persistent level of free circulating anti-LFA1 antibody was detected in 5/8 patients. Despite this, 5 graft failures occurred, with 2 patients experiencing late rejection (days 60 and 97) following HLA-identical transplantation and 3 patients having no engraftment following haplo-mismatched transplant. One other patient died of early sepsis. Only 2 patients (who differed at 1 HLA locus from their donor) are alive with long-term complete chimerism (300 and 315 days). Transient inhibition of recipients' leukocyte functions with an anti-LFA1 antibody did not appear to facilitate engraftment of allogeneic T-depleted marrow transplantation for leukemias.

Adolescent↗
PubMed1989

[In vivo imaging of Hodgkin's lymphomas using monoclonal antibodies].

The Hodgkin- and Reed-Sternberg cell associated monoclonal antibody HRS-1 was labeled with radioactive iodine and injected into 6 patients with Hodgkin's lymphoma for immunoscintigraphic imaging. Four of five patients who received 131I-labeled HRS-1 had a positive immunoscintigram. In the sixth patient, the HRS-1 Mab was labeled with 123I in order to utilize tomoscintigraphy instead of linear scintigraphy. Bony disease was demonstrated by immunoscintigraphy in this patient. These preliminary results demonstrate that immunoscintigraphy with iodine-labeled HRS-1 Mab is feasible and informative in Hodgkin's lymphoma. The real clinical value of immunoscintigraphy in Hodgkin's lymphoma must be determined in a larger series of patients. Several modifications of the technique such as the use of Fab or F(ab')2 fragments should further improve the results.

Adolescent↗
PubMed1989

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↗
PubMed1989

Alternating v repeated postremission treatment in adult acute myelogenous leukemia: a randomized phase III study (AML6) of the EORTC Leukemia Cooperative Group.

The value of a postremission treatment in acute myelogenous leukemia (AML), with alternating combinations of non-cross-resistant drugs, has been prospectively assessed. Of 515 evaluable patients, 347 (67.4%) entered into complete remission (CR), following induction treatment with daunorubicin (DNR), vincristine (VCR), and cytosine arabinoside (ara-C). After one consolidation course, 248 patients were randomized for six courses of intensive maintenance: either repeated treatment with DNR-VCR-ara-C, or alternating treatment where amsacrine (AMSA) was combined with high dose ara-C on cycle 1,3, and 5 and with 5-azacytidine on cycle 2, 4, and 6. Ninety-nine patients were not randomized: 57 were introduced in a bone marrow transplantation (BMT) program, and 42 went off study, mainly for treatment toxicity or refusal. The main prognostic factors for achievement of CR were performance status, cytogenetics, and age, and for the disease-free survival (DFS): age and number of courses to CR. The rate of second remission was fairly high (64%) for patients relapsing off therapy. The DFS appeared identical (median, 53 weeks), in the two randomized arms, the alternating treatment not showing superiority to the repeated one, in spite of an increased toxicity. The median overall survival for patients achieving a CR was 90 weeks. The reason for the failure of alternating maintenance treatment to improve the DFS is probably related to an insufficient dose intensity: five patients who relapsed during maintenance arm B achieved a second CR with a more intensive combination of high-dose ara-C and AMSA. In addition, 60 patients underwent a BMT (43 allogeneic and 17 autologous). The DFS of patients treated with allogeneic BMT tended to be superior to the one obtained with the chemotherapy program. However the overall survival, as well as the event-free survival, seemed equivalent, including patients who relapsed before the planned BMT. Comparisons between allogeneic BMT, autologous BMT, and intensive consolidation during first CR deserve further prospective studies in AML.

Adolescent↗
PubMed1988

Phase II study of mitozolomide (M & B 39,565) in colorectal and breast cancer.

Twenty-two patients with advanced colorectal cancer (CRC) (12 without prior chemotherapy) and fourteen with pretreated breast cancer (BC) were given mitozolomide (MTZ), IV infusion, every six weeks. The starting dose was 90 mg/m2. When it was well-tolerated, dose escalation was done up to 100-115 mg/m2. Toxicity was mild, limited to thrombocytopenia with a median nadir of 1.27 x 10(5) (0.20-4.86). No response was observed in these patients. MTZ, according to these schedule and dosage, does not show activity in human CRC and pretreated BC.

Adenocarcinoma↗
PubMed1988

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↗
PubMed1988

Clinical stages I and II Hodgkin's disease: a specifically tailored therapy according to prognostic factors.

The H5 program in clinical stage (CS) I to II supradiaphragmatic Hodgkin's disease (HD) was tailored to prognostic factors identified in former European Organization for the Research and Treatment of Cancer (EORTC) studies. Among the 494 adult patients included in the study, the 237 patients belonging to the favorable group (H5F) underwent a staging laparotomy (Sx) in order to select the patients who could be treated with limited radiotherapy (RT) only. Thus, 198 patients (84%) with negative laparotomy were treated with RT alone and randomized to either mantle irradiation (M) or extended field mantle plus para-aortic (M + PA) irradiation. Complete remission (CR) was achieved in 99% of the patients. There was no difference in the 6-year relapse-free survival (RFS) rate (74% and 72%, respectively) or survival rate (96% and 89%). Therefore, Sx helped to define those patients who could be treated with M alone in contrast to those who required more aggressive therapy. The 39 patients with positive laparotomy were treated as the unfavorable group (H5U) from onset and randomized to either total/subtotal nodal irradiation (TNI/STNI) or a sandwiched mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) X 3, M irradiation, MOPP X 3 protocol (3M). Although the RFS rate was higher in the 3M arm (100% v 53%; P = .002), the 6-year survival was not significantly different between the two arms (overall, 92%). In the 257 patients with initial unfavorable disease, the Sx was avoided. They were randomized to either TNI/STNI or 3M. In complete responders (96%), the 6-year RFS was 91% in the 3M arm and 77% in the TNI/STNI arm (P = .02). The pattern of failure differed in the two arms: the inverted Y and spleen irradiation controlled occult infradiaphragmatic disease better than MOPP; conversely, less patients begun on MOPP recurred in the involved mantle areas. The difference in 6-year actuarial total survival (TS) (89% and 82%; P = .05 in favor of the 3M arm) was not retrieved after exclusion of the unrelated deaths from the analysis. The two arms produced similar TS in patients under 40 years of age. TNI retains interest, especially in young men wishing to preserve fertility. The overall result shows that when treatment is tailored to initial prognostic factors, excellent results can be obtained in all patient subgroups at minimal morbidity and toxic cost.

Antineoplastic Combined Chemotherapy Protocols↗