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Biomedical subjects

M Hayat

Publications and source records attributed to M Hayat.

At least 109 records · Page 6Linked to original sources
PubMed1988

Evolution of erythrocyte sedimentation rate as predictor of early relapse in posttherapy early-stage Hodgkin's disease.

A retrospective study was undertaken at the Institut Gustave Roussy (IGR) to determine the predictive ability of changes in the erythrocyte sedimentation rate (ESR) during posttherapy periods for early relapse (within 18 months from start of therapy) and long-term survival in Hodgkin's disease (HD). Three hundred one patients with clinical stages (CS) I or II HD entered in the European Organization for Research and Treatment of Cancer (EORTC) clinical trials were included in this study. All relevant data and long-term follow-up were available for these patients. A stepwise logistic regression was performed to assess the prognostic value of ESR changes independent of other prognostic parameters and treatment. The incidence of early relapse was found to be significantly increased in patients in whom ESR remained elevated (greater than 30 mm at one hour) after completion of therapy, regardless of the value before therapy. This was true whether the ESR was elevated in plateau fashion, oscillating between normal and abnormal, or was lower than at onset, but still abnormal. Moreover, early relapse predicted by elevated ESR posttherapy was associated with poor survival despite subsequent initiation of combination chemotherapy. Thus, the persistence of an abnormal ESR appears to be a reliable indicator for high probability of early relapse and subsequent poor prognosis. This might be introduced as a prognostic variable in the design of future therapy programs for HD.

Adult↗
PubMed1988

Ifosfamide/mesna related encephalopathy: a case report with a possible role of phenobarbital in enhancing neurotoxicity.

A case of reversible encephalopathy after one dose of ifosfamide/mesna in an epileptic 15-year-old girl is reported. No other pathology could be responsible for the symptoms. An epilepsy or a toxicity induced by vincristine were discussed. Nevertheless, the possible role of phenobarbital, known to induce hepatic microsomal activity, seems the more probable mechanism.

Adolescent↗
PubMed1988

[Comparison between single-dose and hyperfractionated total-body irradiation for the conditioning of allogenic grafts of the bone marrow. A retrospective study of 54 patients with malignant hematologic diseases].

The present study is a retrospective analysis of 54 patients with hematological malignancies who were treated by total body irradiation (TBI) and allogenic bone-marrow transplantation from 1982-1986. Patients were not randomly assigned to receive either single dose total body irradiation (STBI) (10 Gy x 1-4 cGy/min-lung dose 8 Gy) or hyperfractionated total body irradiation (HTBI) (1,20 Gy x 11-3 fractions/day-lung dose 9 Gy). Thirty one patients received STBI and 23 a HTBI regimen. Despite the presence of a large proportion of patients with a high risk of leukemic relapse in the HTBI group, the incidence of relapse did not differ significantly in the two groups: STBI (16%), HTBI (21%). Lung and liver toxicity were predominant in the STBI group. Interstitial pneumonitis occurred in 45% of the STBI patients versus 13% in the HTBI group. This difference remains significant when adjusted to the incidence of graft versus host disease (GVHD) in the two groups. Three cases of veino-occlusive disease were observed (10%), but only in the STBI group. Even when differences in age and the frequency of GVHD are considered in the two groups, these findings suggest that HTBI is at least as effective as STBI and that toxicity is reduced with this schedule.

Actuarial Analysis↗
PubMed1988

Comparison of total nodal irradiation versus combined sequence of mantle irradiation with mechlorethamine, vincristine, procarbazine, and prednisone in clinical stages I and II Hodgkin's disease: experience of the European Organization for Research and Treatment of Cancer.

The H5 study of supradiaphragmatic Hodgkin's disease in clinical stages I-II consisted of two controlled trials adapted to patients considered to have either favorable or unfavorable characteristics, based on prognostic factors identified in two former studies by the European Organization for Research and Treatment of Cancer. Of 494 patients, 257 who were classified as having unfavorable prognosis qualified for the more intensive treatment and consequently were spared a staging laparotomy. They were randomized either to total nodal irradiation (TNI) (132 patients) or to treatment with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternated with mantle irradiation (MOPP X 3-mantle irradiation-MOPP X 3; 3M) (125 patients). In complete responders (96%), the 6-year relapse-free survival was 77% in the TNI arm and 91% in the 3M arm (P = .02). Relapses in the initially involved and irradiated mantle area were less frequent in patients started on MOPP. The 6-year actuarial total survival (TS) (TNI, 82%, and 3M, 89%; P = .05) appeared to favor the 3M arm, but this difference disappeared when patients dying from causes unrelated to cancer were excluded from analysis. In men less than or equal to 40 years old, there was no difference in relapse-free survival, freedom from disease progression, or TS between the groups receiving TNI and 3M. Thus, TNI is a short and appealing treatment, especially because it preserves fertility. The same observation was true in women less than or equal to 40 years old. In addition, even irradiation less than TNI, which is meant to spare the ovaries, provided a TS similar to that for 3M.

Adult↗
PubMed1987

EORTC trial non-Hodgkin lymphomas.

Results of an EORTC trial (20751) in non-Hodgkin lymphomas are presented. Patients were treated in the same way independent of the histological type. There were 468 patients in the study of whom 124 patients were in stage I (85% 5 year survival), 57 in stage II (55%), 121 in stage III (55%) and 166 in stage IV (45%). Using the Kiel classification the low grade lymphomas were subdivided into two categories: those with a follicular (80% 5 year survival) and with a diffuse cell pattern (50% 5 year survival) with an intermediate prognosis compared with the high grade lymphomas (35% 5 year survival). Treatment was stratified according to stage. In stage I regional radiotherapy was given followed by randomization for maintenance chemotherapy with Vincristine, Cyclophosphamide and Prednisone. No influence in survival was seen (85% at 5 years), although disease free survival was better in the maintenance chemotherapy group (75% vs 55% at 5 years). In stage II regional radiotherapy was followed, after randomization, by transdiaphragmatic irradiation, all patients received maintenance chemotherapy. The group was too small to draw conclusions about the effect of this treatment. Primary radiotherapy in stage II disease with diffuse histology gave bad results. Patients in stage III and IV were treated with 8 courses of chemotherapy with Adriamycin, VM26, Cyclophosphamide and Prednisone, given in two different time schedules. Iceberg radiation was then given to areas with initially large or slowly responding disease. All patients had maintenance chemotherapy. No difference was found for the 2 chemotherapy schedules in remission rate, disease free interval and survival. In stage III and IV patients with a follicular lymphoma have a longer relapse free interval and total survival (39% and 68% at 5 years) compared with those with a lymphoma diffuse histology (19 and 30% at 5 years). Patients with stage IV disease due to bone marrow involvement only had a better prognosis compared with stage IV disease for other reasons.

Adolescent↗
PubMed1987

Clinical pharmacology of high-dose etoposide associated with cisplatin. Pharmacokinetic and metabolic studies.

Twelve patients were treated with high-dose etoposide give alone or in combination with cisplatin during a clinical trial. We had previously observed, in some subjects who received a combination of high-dose etoposide (350 mg/m2/day X 5 days) and cisplatin (40 mg/m2/day X 5 days), delayed hematological recovery after autologous bone marrow transplantation. Therefore we investigated the pharmacokinetics of etoposide and did not find any drug interaction with cisplatin. In four of these patients we also monitored etoposide salivary excretion and found saliva to plasma ratios in the range 0.003-0.25. The secretion of etoposide into saliva may be of concern if we consider that peroxidases in salivary glands are able to oxidize the drug leading to free radicals. In vitro experiments showed that sulfhydryl compounds are able to inhibit the formation of the etoposide radical. Furthermore, we were able to detect the presence of a new biotransformation product of etoposide in plasma samples of some patients. Fast atom bombardment liquid chromatography-mass spectrometry allowed us to identify this metabolite as the etoposide aglycone. The presence of this derivative in plasma 48 h after the last injection prompted us to delay autologous bone marrow transplantation to 72 h after the end of treatment, since the aglycone is cytotoxic and able to induce DNA strand breaks mediated by topoisomerase II.

Adult↗
PubMed1987

Incubation of autologous bone marrow graft with ASTA Z 7557: comparative studies of hematological reconstitution after purged or nonpurged bone marrow transplantation.

Thirty-three patients with advanced solid tumors were treated by high-dose chemotherapy (combined high-dose melphalan), followed by cryopreserved autologous bone marrow transplantation (ABMT). Thirteen of them had bone marrow (BM) tumor involvement at diagnosis, and BM harvest was purged with 50 micrograms/ml ASTA Z 7557 before cryopreservation. Following incubation, in vitro growth of granulomonocytic colony-forming cells (GM-CFC) was regularly inhibited (greater than 99%). Hemopoietic reconstitution after purged and nonpurged ABMT was studied. All patients experienced engraftment. However, peripheral leukocyte and granulocyte recoveries were delayed significantly in patients receiving purged BM (mean 27 and 26 days) compared with those observed in patients receiving nonpurged BM (mean 18 and 18 days). These results confirm that purged BM, despite GM-CFC depletion after in vitro treatment, ensures engraftment after high-dose chemotherapy, but prolonged pancytopenia is observed and postgraft hemopoietic recovery is delayed. A clinical trial is necessary to evaluate the efficiency of the purging technique in eradicating residual tumor cells.

Adult↗
PubMed1987

[Chemo-radiotherapy combination in small cell bronchial carcinomas. Limitations and results in 109 patients treated with an alternating protocol].

One hundred and nine patients with limited small cell lung carcinoma were entered in a phase II study alternating six cycles of combination chemotherapy and three courses of mediastinal radiotherapy. Chemotherapy consisted of doxorubicin 40 mg/m2 day 1, etoposide 75 mg/m2 days 1, 2, 3, cyclophosphamide 300 mg/m2 days 3, 4, 5, 6, and methotrexate 400 mg/m2 day 2 (+folinic acid rescue) or cisplatin 100 mg/m2 day 2. The total mediastinal radiation dose was 45 or 55 Gy. A 6 to 8 cycle maintenance chemotherapy followed this induction protocol. The complete remission rate at the end of the induction therapy was 79%. The local recurrence rate was 25% and the distant metastases rate was 52%. Median survival is 17.2 +/- 1.2 months and survival rate at 3 years is 26%. Lethal toxicity occurred in 3% of patients during induction therapy, and long term survivors are being evaluated. Our results justify further investigations with this alternating schedule.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[High-doses chemotherapy followed by bone marrow autograft in the treatment of small cell bronchial cancer].

Nineteen patients were treated with high dose chemotherapy followed by an autologous bone marrow transplantation. The chemotherapy regimen was an association of BCNU, procarbazine, etoposide, melphalan. Six patients had a progressive disease; 4 short-term complete remissions were observed. In 13 responding patients, 6 maintained complete remissions were noted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[Non-Hodgkin's malignant lymphomas of the nasopharynx. Apropos of 24 cases treated at the Institut Gustave-Roussy].

Twenty-four patients with non Hodgkin's lymphoma of nasopharynx were treated in the Institut Gustave-Roussy, France, between 1976 and 1983. Mean age of patients was 53 years and the male/female sex ratio was 2. Symptomatology was immediately suggestive of a lesion in the nasopharynx in 21 of the 24 patients, and histology gave an unfavorable prognosis (diffuse large cell tumors) in 71% of cases. Complete investigations showed the lymphoma to be relatively limited in extent in the majority of cases (68% of stages I and II). These findings are in agreement with published reports. The 4 patient with stage I disease were treated by irradiation alone and are all alive without recurrence after 43 months. The 11 patients with stage II lesions received combined chemo-radiotherapy, and at 42-month follow up 8 were alive without recurrence (1 patient died of intercurrent illness). Results of conventional chemotherapy (CHVmP) in patients with stages III and IV were disappointing, however: only one patient survived for 60 months (after a cerebral recurrence treated by irradiation). Although current therapy is effective for stage I and II lesions, patients with stages III and IV require more aggressive therapy recently developed: heavy multiple chemotherapy, and even intensive chemotherapy-total body irradiation and bone marrow graft.

Adult↗
PubMed1986

A randomized comparison of maintenance treatment with androgens, immunotherapy, and chemotherapy in adult acute myelogenous leukemia. A Leukemia-Lymphoma Group Trial of the EORTC.

Twenty-three European centers participated in a randomized clinical trial (AML-5) to study the effect of androgens and immunotherapy during maintenance in adult acute myelogenous leukemia. Induction treatment consisted of Adriamycin (doxorubicin) 50 mg/m2 day 1, vincristine VCR 1 mg/m2 day 2, and cytosine arabinoside 80 mg/m2 every 12 hours by push injection days 3-9. Patients in complete remission were randomized into four groups: (1) 6-mercaptopurine 70 mg/m2 days 1-14, methotrexate 15 mg/m2 twice weekly days 15-28, and reinduction with daunorubicin 35 mg/m2 and vincristine 1 mg/m2 day 29; (2) chemotherapy as in group 1 plus stanozolol 0.15 mg/kg/day; (3) 6-thioguanine 70 mg/m2 orally on 4 consecutive days and cytosine arabinoside 80 mg/m2 subcutaneously day 5 every week; and (4) chemotherapy as in Group 3 plus irradiated blast cells treated with neuraminidase. Three hundred forty-eight patients were eligible and 295 were evaluable. The median age was 45 yrs. A complete remission was achieved in 64% of the patients, with 158 complete remissions randomized. Patients not randomized and patients receiving bone marrow transplantation (BMT) were analyzed separately. There was no difference in disease-free survival (DFS) or survival in the four maintenance arms. For patients reaching complete remission, the median DFS was 40 weeks, and median survival was 22 months with 30% surviving at 4 years. The overall survival was 18% at 4 years. There was no beneficial effect for DFS or survival by adding either immunotherapy or androgens to chemotherapy during maintenance. However, patients receiving immunotherapy seemed to have a higher rate of responses to reinduction after relapse than those in the other treatment arms.

Adolescent↗
PubMed1986

Characterization of antileukemia cells' cytotoxic effector function. Implications for monitoring natural killer responses following allogeneic bone marrow transplantation.

We have studied here cytotoxic function of three cloned cell lines--TC12, 48, and 50--derived from circulating lymphocytes that were potentially able to eliminate residual tumor cells in a patient transplanted for treatment of acute lymphocytic leukemia. These cloned cells, which have both phenotypic and functional characteristics of natural killer lymphocytes, were tested in chromium release assays against a panel of 16 uncultured populations of leukemia cells. In addition, their activity was compared with that of cloned and uncloned NK cells from normal individuals. It was found that TC clones induced a much weaker degree of killing against fresh tumor cells compared with conventional NK target cell lines such as K562 or MOLT 4. In addition, there was great heterogeneity in their individual lytic capacity against the various leukemia blasts (TC12, 48, and 50 cells killed in a significant fashion, respectively 7, 1, and 4 of the 16 leukemias), reflecting the functional diversity of normal NK cell populations. Thus, for a fraction of leukemias, there was no correlation between lytic ability of TC cells and that of uncloned lymphokine-activated large granular lymphocytes from normal peripheral blood. Together, these results support the view that direct identification of patients' cytotoxic lymphocytes screened against in vivo relevant tumor cells is necessary to evaluate potentially beneficial immunologic responses in the context of bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed1986

High-dose melphalan with or without marrow transplantation: a study of dose-effect in patients with refractory and/or relapsed acute leukemias.

Dose-effect relationships of high-dose melphalan were evaluated in 37 patients with measurable relapsed or refractory acute leukemias. Thirteen patients (Group 1) received 70-100 mg/m2 of melphalan without marrow rescue and 24 patients (Group 2) received 140-180 mg/m2 of melphalan followed by marrow transplantation. Patients in both groups were comparable with respect to age, sex, diagnosis, and status of the leukemia. The complete remission rate was 23% in Group 1 versus 75% in Group 2 (P less than 0.01). Hematological recovery of remission patients was not statistically different in either group. Nonhematological toxicity was comparable in the two dose ranges examined. These results demonstrate the existence of a dose-response effect of high-dose melphalan regimens in relapsed acute leukemias, without marked increases in nonhematological toxicity with these doses.

Acute Disease↗
PubMed1986

Modified chemotherapy with carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) and autologous bone marrow transplantation in 24 poor-risk patients with acute lymphoblastic leukemia.

Twenty-four poor-risk patients with acute lymphoblastic leukemia received a modified regimen of carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) followed by autologous bone marrow transplantation (ABMT). Nineteen patients were in second or subsequent complete remission (CR) when treated with this regimen; 3 died early, 2 died of pneumonia in CR, 11 relapsed within 3 months (median), and 3 remain in CR with no maintenance therapy 14-24 months after ABMT. Of the 5 patients with measurable disease who were treated, 3 had CR and 1 remains in CR without maintenance therapy more than 28 months after ABMT. The toxicity of this regimen was acceptable, but late pulmonary toxic effects remain a major concern. These results are poor in terms of efficacy, and new effective methods of eradicating acute lymphoblastic leukemia in patients with poor prognosis should be investigated.

Adolescent↗