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Biomedical subjects

Y Merrouche

Publications and source records attributed to Y Merrouche.

16 recordsLinked to original sources

Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma.

Interleukin (IL) 6 was measured in the serum of 138 patients with metastatic renal carcinoma before the initiation of IL-2 treatment. IL-6 was detectable in 66 patients with renal cancer (48%) and in only 8 of 70 normal adults (11%). Serum C reactive protein (CRP) and IL-6 levels are correlated, suggesting that IL-6 is involved in CRP increase in these patients. The interval between diagnosis of the primary tumor and metastasis was shorter in patients with a detectable serum IL-6 and/or serum CRP level greater than 50 mg/liter. Serum IL-6 and CRP levels were higher in subgroups of patients previously defined as having a poor life expectancy according to the Eastern Cooperative Oncology Group criteria. Pretreatment concentrations of IL-6 and CRP were higher in patients who experienced progressive disease after IL-2 treatment. Patients with detectable IL-6 had a shorter survival from the beginning of IL-2 treatment than patients without circulating IL-6 (median, 8 versus 16 months). Similarly, the median survival from the beginning of IL-2 therapy of patients with CRP levels greater than 50 mg/liter was 6 months, compared to 16 months in those with CRP levels below this threshold. None of the 21 patients with serum IL-6 concentrations greater than 300 pg/ml achieved response to any of the three IL-2 regimens. This subgroup has a median survival of 5 months after IL-2 treatment and consisted of 15% of the patients in our series. These results indicate that serum IL-6 and CRP levels are adverse prognosis factors in patients with metastatic renal cell carcinoma. Serum IL-6 level could help in the selection or stratification of the patients in future IL-2 trials.

Adult

Intravenous interleukin-2 in patients over 65 with metastatic renal carcinoma.

The present study was designed in order to evaluate the response rate and the toxicity of continuous infusion of Interleukin 2 (IL2) in patients over 65 with metastatic renal cell carcinoma. Twenty-five patients, median age 69 (range 65-77), without any prior systemic anticancer therapy received a continuous infusion of IL2 at a dose of 18 x 10(6) iu m-2 d-1 for 2 periods of 5 days separated by a 6 day break. Toxicity was not different compared with younger patients (e.g. fever, hypotension, rise in creatinine level), except for cardiac toxicity which was of great concern. Despite normal cardiac tests prior to inclusion into the study, abnormalities of the cardiac rhythm ranging from tachycardia to ventricular extrasystoles occurred in 44% of the patients and IL2 cardiac toxicity was responsible for one toxic death. Three objective responses, i.e. one partial and two complete persistent responses, were seen in 22 evaluable patients. Thus, if age does not seem to modify the potential for response to IL2 therapy, cardiac toxicity appears as a limiting factor for intravenous schedules of IL2.

Aged

Retroviral gene therapy and its application in oncohematology.

A symposium entitled "Foetal and Neonatal Cell Transplantation and Retroviral Gene Therapy" recently organized under the aegis of the Mérieux Foundation in Annecy, France, brought together 100 scientists and clinicians from European countries and the United States. The last day of the meeting focused on retroviral gene therapy in oncohematology. The speakers provided the basis for therapeutic applications of gene transfer and showed practical directions to be followed in the near future. Although it may be mainly restricted to in vitro manipulation of human cells at start, gene therapy is already applicable to the treatment of genetic disorders, cancer, and viral infections. The reality of gene therapy was well illustrated by the nature of the questions raised by clinicians and scientists during the meeting.

Animals

[Gene transfer and gene therapy].

The application of gene transfer technology to human gene therapy has been intensively investigated during the last decade. The first human clinical trials in adenosine deaminase deficiency and metastatic melanoma recently demonstrated the feasibility and safety of using retroviral gene transduction for human gene therapy. Many problems remain to be solved for a better understanding of the functioning of genes to be transferred, a better efficiency of gene transfer and genetic correction by site-specific targeting in vivo, a better knowledge of the biological properties of target cells such as totipotent hematopoïetic stem cells. Clinical developments are expected in genetic diseases (immunodeficiency, thalassemia, hemophilia) and non genetic disorders (lymphokine gene therapy for cancer).

Child

[Analysis of changes in serum levels of TNF, IL-1 and IL-6 during administration of IL-2. Correlation with clinical response to treatment].

We have investigated the serum concentrations of TNF, IL-1 and IL-6 in 49 patients with metastatic renal carcinoma receiving interleukin 2 (IL-2) or a combination of IL-2 and interferon alpha (IFN). Our results demonstrate that IL-2 and/or IFN induce an increase of serum concentrations of IL-1 and TNF in 95% and 75% of the patients respectively. Serum IL-6 levels increase in 44% of the patients. Serum concentrations of IL-1 and TNF remain elevated 48 hours after the end of IL-2 infusion. IL-1 and TNF levels are higher in patients receiving a combination of IL-2 and IFN. TNF and IL-1 levels in serum are significantly higher in responders to IL-2 treatment 48 hours after the end of IL-2 infusion. These two biological criteria enable a subgroup of patients with a very low response rate to IL-2 to be defined. The persistent increase of these cytokines in serum indicates a persistent activation of the immune system lasting after the end of IL-2 treatment which could be involved in the antitumor response.

Adenocarcinoma

Intravenous interleukin-2 just after high dose BCNU and autologous bone marrow transplantation. Report of a multicentric French pilot study.

This multicentric pilot study was conducted in order to evaluate the feasibility of early interleukin-2 (IL2) after high dose chemotherapy requiring autologous bone marrow transplantation (ABMT). BCNU at 800 mg/m2 was followed, 3 days later, by the reinjection of the bone marrow cells. At day 4, IL2 at 18 x 10(6) i.u./m2/day was given as a continuous infusion during a minimum of 6 days (first phase of study) or for 6 more days after 1 day break (second phase of the study). Twenty patients were included. Toxicity was not negligible, with one toxic death, but IL2 therapy does not damage the haematological recovery of most patients. However, a 6-day IL2 treatment period only appears tolerable. In 18 evaluable patients, three responses were observed: one complete response (CR) of short duration in a non-Hodgkin's lymphoma, one CR (24 months +) and one partial response (PR) (6 months) in two patients with metastatic gastric adenocarcinoma. This study confirms that IL2, restricted to a 6-day treatment period, is feasible immediately after high-dose chemotherapy requiring ABMT without haematological problem in most patients. The response rate was unexpected for a pilot study and this combined therapy obviously requires further study.

Adult

[Periarteritis nodosa related to hepatitis B virus. Determination of a new therapeutic strategy: 13 cases].

The treatment and prognosis of periarteritis nodosa associated with hepatitis B virus were reconsidered from a series of 13 patients representing 32.5 per cent of the 40 patients with periarteritis nodosa admitted during the same period. HBs and HBe antigens were present in every case, and hepatitis B virus replication was demonstrated by the finding of viral DNA in serum. One patient had anti-HBc IgM's. Five patients were treated with corticosteroids, cyclophosphamide and occasional plasma exchanges. All were cured or achieved complete remission. Eight patients were treated with plasma exchanges and vidarabine, either as first-line therapy (3 cases) or after failure of corticosteroids and/or immunosuppressants (5 cases). This treatment was clinically effective in 5/8 cases, including 3 with seroconversion. The 2 patients in whom the combined treatment failed were given corticosteroids; one of them also had plasma exchanges. The 8th patient died after a few days of treatment. Eleven of the 13 patients are still alive and either cured or in complete remission. Two patients who developed severe chronic hepatitis after steroids were discontinued received vidarabine alone: arrest of viral replication was obtained in both cases, with emergence of an anti-HBe (but not anti-HBs) antibody. The overall positive virological response rate to vidarabine alone or combined with plasma exchanges was 50 per cent. When vidarabine was prescribed as treatment of acute periarteritis nodosa (the 2 cases where it was used for chronic hepatitis being excluded), this response rate was 37.5 per cent. This, in patients with periarteritis nodosa associated with hepatitis B virus immunosuppressive drugs should be withdrawn and replaced by plasma exchanges and antiviral agents. This would be the first-line treatment to be replaced by corticosteroid therapy if it fails.

Combined Modality Therapy

[Interactions between HIV virus and the nervous system: recent pathogenic data and hypotheses].

Disorders of the nervous system frequently complicate Acquired Immune Deficiency Syndrome (AIDS). They may be related to the development of opportunistic agents (toxoplasmosis, cryptococcossis, cytomegalovirus, JC Virus), or primary CNS lymphoma. There is also a constellation of neurologic disorders which may result from direct Human Immunodeficiency Virus (HIV) replication in the CNS and HIV has been found in brain and CSF of numerous patients suffering from AIDS. The precise cellular localization of HIV is not known, but the macrophage seems to be a strong candidate for HIV replication in CNS.

Acquired Immunodeficiency Syndrome

[Treatment of cancer of the kidney with interleukin 2 in adults, the Lyon experience].

Like interferon-alpha, interleukin 2 (IL2) is active on metastatic kidney cancers, which are regarded as chemoresistant tumors. Out of 20 to 30% objective responses, 5 to 10% complete remissions are reported with various IL2 delivery schedules. The considerable toxicity is well mastered at present, thus allowing treatment in non-intensive care departments, or even in an ambulatory mode for subcutaneous administration. Even though Interleukin 2 has been authorized for sale in France, optimal mode of administration, the role of the IL2-interferon-alpha combination or the predictive factors of response to treatment still raise many questions.

Drug Therapy, Combination