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Biomedical subjects

M Hayat

Publications and source records attributed to M Hayat.

At least 55 records · Page 3Linked to original sources
PubMed1993

[Hematopoietic growth factor (GM-CSF) after autologous bone marrow transplantation. A randomized, double-blind, multicenter study in 91 cases of non-Hodgkin's malignant lymphomas].

To a great extent, the risks of autologous bone marrow transplantation are related to neutropenia. Although the efficacy of the recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) on neutrophil recovery has appeared in numerous open trials, only a few randomized studies have hitherto been published. Ninety-one patients with non-Hodgkin's malignant lymphoma treated with ablative chemotherapy followed by purged or unpurged bone marrow transplantation were entered in a placebo-controlled, double-blind randomized study; 44 patients received GM-CSF (E. coli) in doses of 250 micrograms/m2/day, and 47 received a placebo. Treatment was administered daily as continuous infusion started on the day of transplantation and pursued until the absolute number of neutrophils reached 0.5 x 10(9)/l during 7 days or, if this failed, during 30 days. The median time of neutrophil recovery was 14 days in patients on rhu GM-CSF and 21 days in patients on placebo (P < 0.0001). Patients who received a mafosfamide-purged bone marrow also had a rapid neutrophil recovery (median: 16 days versus 20.5 days; P = 0.013). The stay in hospital was shorter in the rhu GM-CSF group (median: 23 days versus 28 days; P < 0.05). No significant difference in the number of days with fever, infections, antibiotics administered and overall survival was detected between the two groups. The main toxicity ascribable to rhu GM-CSF was a capillary leakage syndrome found in 3 patients. Thus, after purged or unpurged autologous bone marrow transplantation rhu GM-CSF significantly reduces the duration of both neutropenia and hospital stay.

Adolescent↗
PubMed1993

High-dose chemotherapy with etoposide, cyclophosphamide and escalating dose of carboplatin followed by autologous bone marrow transplantation in cancer patients. A pilot study.

25 patients with poor-prognosis malignancies were treated with a combination of fixed-dose etoposide (1750 mg/m2), cyclophosphamide (6400 mg/m2) and escalating doses of carboplatin (from 800 to 1600 mg/m2) followed by autologous bone marrow transplantation (ABMT). The median duration of granulocytopenia (< 500/mm3) and thrombocytopenia (< 20,000/mm3) was 23 days and 20.5 days, respectively. The main non-haematological toxicity was gastro-intestinal, with moderate to severe diarrhoea in 15 patients. No significant renal toxicity was observed. 2 patients died early due to toxicity. The overall response rate was 58% including 42% having complete responses. 4 of the 25 patients are alive with no evidence of disease at 22, 27, 40 and 43 months after ABMT. The encouraging antitumoral activity of this regimen makes it a good candidate for intensified chemotherapy in patients with various malignancies. Toxicity is acceptable and may be reduced in the near future with the widespread use of haematopoietic growth factors.

Adolescent↗
PubMed1993

Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group.

PURPOSE: To compare (1) clinical staging and irradiation alone versus staging laparotomy and treatment adaptation in patients with a favorable prognosis (H6F); (2) two combined modalities in patients with an unfavorable prognosis (H6U). PATIENTS AND METHODS: The H6F trial (n = 262) consisted of randomization to clinical staging plus subtotal nodal irradiation (STNI) or to staging laparotomy plus treatment adaptation (adjuvant chemotherapy [CT] only in the 33% with negative laparotomy). The H6U trial (n = 316) consisted of no laparotomy, randomization to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), and mantle irradiation. RESULTS: In the H6F trial, 6-year freedom from progression (FFP) rates (78% v 83%; P = .27) were similar in clinical and laparotomy stagings, respectively. Survival rates were 93% and 89%, due to laparotomy-related deaths. In the H6U trial, the ABVD arm had superior results (6-year FFP rate, 88% v 76%; P = .01), but they were not significant for survival (91% v 85%; P = .22). CT discontinuation due to hematologic intolerance occurred more often with MOPP (14.5% v 7.3%). Decrease of the pulmonary vital capacity ([VC] < 70% of the theoretic value) was observed more frequently after ABVD than after MOPP (12% v 2%; P = .08), with two lethal pulmonary insufficiencies occurring in the ABVD arm. No modification of the isotopic left ventricular ejection fraction (LVEF) occurred. Gonadal toxicity was less in the ABVD arm. CONCLUSION: Early-stage patients benefit from treatment adaptation to initial characteristics in terms of tumor control and late toxicities. Staging laparotomy before STNI may be deleted even in favorable patients at no cost to survival or FFP. In unfavorable patients, ABVD achieved better results than MOPP, at lower hematologic and gonadal cost. Therefore, despite its pulmonary toxicity, ABVD is the best choice to design improved CT regimens associated with mantle irradiation.

Adolescent↗
PubMed1993

[Thrombosis and cancer].

Thrombotic episodes represent the second cause of mortality in cancer patients. These complications are more frequent with some adenocarcinomas and hematologic malignancies. The mechanisms of pathogenesis are complex inducing an unbalanced function of the antithrombotic system. According to the type of tumor and the underlying mechanism, clinical manifestations are generally severe. The diagnosis of these thromboses are essentially clinical or radiological. The treatment is based on heparinotherapy, thrombolytic agents or eventually on surgery, which is not discussed here.

Heparin↗
PubMed1993

Should vancomycin be used empirically in febrile patients with prolonged and profound neutropenia? Results of a randomized trial.

OBJECTIVES: We conducted a randomized trial with ceftazidine alone or associated with amikacin or vancomycin to investigate the efficacy of the daily 3 g dosage of ceftazidime and the efficacy of monotherapy with ceftazidime and to determine if vancomycin should be added empirically. METHODS: Patient inclusion criteria were: age over 10 years, therapeutically-induced neutropenia and fever for at least three hours above 38.5 degrees C in absence of a clear non-infectious aetiology. Patients were randomized into three groups: group C, ceftazidime alone 3 g/day; group CA, ceftazidime 3 g/day plus amikacin 15 mg/kg/day; or group C, ceftazidime 3 g/day plus vancomycin 1.5 g/day. RESULTS: Results from one hundred and two episodes of fever were analyzed. The underlying diseases were haematological malignancies (89 patients) and solid tumours (13 patients). The median duration of neutropenia (< 0.5 x 10(9) PMN/L) was 18 days and the minimum duration of 7 days. The main criterion for the analysis of efficacy was the onset of a major infectious event, i.e. death related to documented or suspected infection and any infectious event considered life-threatening or hindering future treatment of the underlying disease. Eight (22%) patients in group C developed major infectious events compared with four (13%) in group CA and none in group CV (p < 0.01). Major infectious events were mainly due to Gram-positive organisms, particularly Streptococcus species. CONCLUSION: We conclude that: 1) ceftazidime alone and in association with amikacin is effective in preventing Gram-negative major infectious events; and 2) vancomycin should not be added only when a Gram-positive infection is documented, but used empirically.

Adolescent↗
PubMed1992

Recombinant human granulocyte-macrophage colony-stimulating factor after high-dose chemotherapy and autologous bone marrow transplantation with unpurged and purged marrow in non-Hodgkin's lymphoma: a double-blind placebo-controlled trial.

The toxicity of autologous bone marrow transplantation (ABMT) is correlated to neutropenia. Although recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) seems to hold promise in accelerating neutrophil recovery, few analyses from randomized studies are presently available. Ninety-one patients with non-Hodgkin's lymphoma receiving high-dose ablative chemotherapy followed by ABMT with unpurged or purged marrow were included in a randomized, double-blind, placebo-controlled trial. Forty-four patients received 250 micrograms rhu GM-CSF (Escherichia coli)/m2 and 47 patients received placebo. Treatment was administered daily as continuous infusion from day of ABMT until the absolute neutrophil count (ANC) reached 0.5 x 10(9)/L for 7 days or until day 30, whichever was first. With rhu GM-CSF, 50% of the patients reached an ANC count greater than 0.5 x 10(9)/L at day 14 as opposed to day 21 with placebo (P less than .0001). Patients transplanted with marrow purged by mafosfamide also recovered earlier when treated with rhu GM-CSF (16 v 20.5 days, P = .013). The hospitalization duration was shorter in the rhu GM-CSF group (median, 23 v 28 days, P less than .05). No difference was observed in fever, number of infections, and antibiotic administration between the two groups. The major adverse event ascribed to rhu GM-CSF was a capillary leak syndrome in three patients graded as severe in two patients, moderate in one, and reversible in all three patients. In addition, one patient in the rhu GM-CSF group died suddenly with no explanation. In long term follow-up, the relapse rate was identical in both groups and there was no significant difference in the number of deaths at 1 year (12 with rhu GM-CSF v 9 with placebo), although deaths seemed to occur slightly earlier in the rhu GM-CSF group. We conclude that after ABMT with purged or unpurged marrow, rhu GM-CSF (E coli) significantly reduces neutropenia duration and hospitalization stay. A positive causative relation between the study drug and/or its mode of application with an increased toxicity as compared with GM-CSF from other sources and/or other modes of application cannot be deduced from the experiences in this study. Additional randomized trials would be necessary for an appropriate answer.

Adolescent↗
PubMed1992

Serum levels and receptor expression of tumor necrosis factor-alpha following human allogeneic and autologous bone marrow transplantation.

We have investigated tumor necrosis factor-alpha levels in serum samples of patients before and after allogenic (16 patients) or autologous (8 patients) bone marrow transplantation. A sensitive immunoradiometric assay for monitoring levels of endogenous tumor necrosis factor-alpha was used. The serum levels of tumor necrosis factor-alpha were found to be relatively low (ranging from less than 15 to 77 pg/ml). Among 13 patients having graft-versus-host disease following allogeneic bone marrow transplantation 8 patients did not have detectable tumor necrosis factor-alpha (less than 15 pg/ml) while 4 out of 8 patients undergoing autologous bone marrow transplantation had detectable tumor necrosis factor-alpha levels (15 pg/ml), indicating a lack of correlation between tumor necrosis factor-alpha serum levels and the occurrence of graft-versus-host disease. Because the tumor necrosis factor-alpha levels detected in patient sera could be regulated by TNF-receptor expression, the presence of TNF-receptor on patients' peripheral blood mononuclear cells was also studied using fluorescent liposome-conjugated tumor necrosis factor-alpha and immunofluorescence analysis. Our data indicate that peripheral blood mononuclear cells of some patients receiving either autologous or allogeneic bone marrow transplantation expressed significant levels of TNF-receptors, suggesting a lack of correlation between TNF-receptor expression and graft-versus-host disease development.

Bone Marrow Transplantation↗
PubMed1992

Acute myelogenous leukemia with T-cell features.

From May 1985 to June 1990, 94 newly diagnosed cases of acute myelogenous leukemia (AML) were treated at the Institut Gustave-Roussy, of which four (4.3%) demonstrated mixed cell lineage. All these cases were morphologically and cytochemically considered as myelogenous leukemias according to the FAB classification. Immunophenotyping revealed in all four cases that the blast population had T-lymphoid (CD2, CD5, CD7 and cytoplasmic CD3) markers. In three of these cases, blast cells co-expressed myelogenous CD13 and CD33 markers. Cytogenetic analysis of the blast cells revealed a normal karyotype in all cases. The response to therapy has been poor. The two patients initially treated with a regimen usually used for AML did not achieve complete remission. By contrast, in three cases, complete remission was obtained with a drug combination used for lymphoblastic leukemia (in one case after failure of first line AML regimen). Only one patient remained disease-free for more than 18 months. We conclude that this form of leukemia is a distinct biological and clinical entity and may benefit form alternative therapy.

Adolescent↗
PubMed1991

Sequence analysis of the simian foamy virus type 1 genome.

We have cloned the simian foamy virus type 1 genome (SFV1) and determined its nucleotide sequence. Analysis of this genome reveals, in addition to the usual genes encoding retroviral capsid, reverse transcriptase, and envelope protein (respectively, gag, pol, and env), two open reading frames (ORFs) between env and the long terminal repeat with partial homology to the human foamy virus (HFV) bel1 and bel2 genes. The first ORF could code for a polypeptide of 312 amino acids (aa) showing 40% homology with the HFV bel1 putative gene product. A more detailed analysis showed that the protein encoded by this ORF would have features characteristic of known trans-activating proteins. The second ORF could code for a polypeptide of 403 aa showing 38% homology with the putative HFV bel2 gene product. Moreover, the 5' extremity of the RNA genome can be folded into a secondary structure identical to the Tat-response element of human immunodeficiency viruses. A phylogenetic tree of retroviruses, including SFV1 and HFV, was constructed. It showed at the molecular level that Spumavirinae, previously classified on the basis of their morphology and their biological properties, constitute a separate group. The homology between SFV1 and HFV reaches 89% in the reverse transcriptase domain of the pol gene. but is much smaller in other parts of the genome.

Amino Acid Sequence↗
PubMed1991

Erythrocyte sedimentation rate predicts early relapse and survival in early-stage Hodgkin disease. The EORTC Lymphoma Cooperative Group.

OBJECTIVE: To assess the value of an elevated (greater than 30 mm/h) Westergren erythrocyte sedimentation rate (ESR) for predicting early relapse and survival after therapy in patients with clinical stage I or II Hodgkin disease. INTERVENTIONS: We studied 772 patients with early-stage Hodgkin disease who had participated in two separate multicenter clinical trials. Both trials used modern field radiotherapy and, in some patients, multi-agent chemotherapy. MAIN RESULTS: The ESR patterns were based on pretherapy and post-therapy assessments: pattern 1, always normal (n = 261); pattern 2, elevated before therapy but normal immediately after therapy (n = 121); pattern 3, elevated before therapy but normal within 3 months after therapy (n = 89); pattern 4, always elevated (n = 48); pattern 5, normal before therapy but oscillating between normal and elevated after therapy (n = 150); pattern 6, elevated before therapy but oscillating between normal and elevated after therapy (n = 130). By multivariate analysis, independent of whether or not patients received chemotherapy in the initial therapy protocol, ESR patterns 4, 5, and 6 were shown to be the best predictors for early relapse and survival when patients were stratified according to the type of chemotherapy received and the number of involved nodal areas. Patients with ESR pattern 4 had a relative risk for death seven times that of patients with patterns 1, 2, or 3. Early relapse was the second most important factor predicting death, irrespective of ESR; patients with early relapse and ESR patterns 1, 2, or 3 had a relative risk for death of 4.5, and those with early relapse and ESR patterns 4, 5, or 6 had a relative risk for death of 15. Whether or not chemotherapy was given initially did not change the relative risk, which shows that ESR, not initial therapy, was the predictor for early relapse and death due to Hodgkin disease. CONCLUSION: An unexplained elevated ESR after therapy, especially after modern radiotherapy, independent of other factors, strongly suggest the presence of aggressive and resistant Hodgkin disease. An elevated ESR is predictive of early relapse and poor prognosis; its presence justifies early aggressive therapy.

Adult↗
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

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

Long-term survivors after salvage high dose chemotherapy with bone marrow rescue in refractory germ cell cancer.

Between April 1984 and May 1985, 17 heavily pretreated patients with relapsing or refractory germ cell tumours were treated with cisplatin 40 mg/m2/day, days 1-5; etoposide 350 mg/m2/day, days 1-5; cyclophosphamide 1600 mg/m2/day, days 2-5 and autologous bone marrow transplantation on day 8 as consolidation of conventional salvage chemotherapy. None of the 11 refractory patients and 4 of the 6 responders to prior salvage treatment are long-term survivors at 68, 72, 74 and 74 months. Mean aplasia duration was 17 days and there were 7 documented episodes of septicaemia in 17 febrile patients. 1 patient died of treatment. Among the 4 survivors, 2 patients have a sustained grade II invalidating neuropathy. We conclude that this regimen is not recommended as salvage therapy in refractory patients but may be a useful consolidation treatment in patients responding to conventional salvage chemotherapy.

Adolescent↗