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Biomedical subjects

D Baume

Publications and source records attributed to D Baume.

52 records · Page 3Linked to original sources
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

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

Antibiotic treatment and intestinal colonization by Pseudomonas aeruginosa in cancer patients.

To determine whether antibiotic treatment increases the risk of colonization by Pseudomonas aeruginosa, we performed a case-control study comparing antibiotic exposure in cancer patients colonized by P. aeruginosa and in noncolonized controls. Of 88 patients, 76 had been exposed to at least one antibiotic, but colonization was not statistically associated with exposure to any specific antibiotic treatment, administered orally or parenterally, alone or in combination.

Adolescent↗
PubMed1988

[Antibiotic therapy protocol using ceftazidime 3g/day alone or in combination with vancomycin or amikacin. In febrile episodes in neutropenic patients].

In a preliminary study of 21 febrile episodes in neutropenic patients ceftazidime used as empirical treatment in doses of 3 grams per day succeeded in controlling fever in 74 per cent of the cases. Laboratory studies performed in patients with Gram-negative septicaemia showed clinically effective plasma concentrations of the antibiotic. A trial of ceftazidime (3 g/day) administered alone or combined with amikacin or vancomycin is currently in progress in two medical centres. No statistically significant conclusions could be reached from an intermediate study.

Agranulocytosis↗
PubMed1988

Salvage chemotherapy in refractory germ cell tumors with etoposide (VP-16) plus ifosfamide plus high-dose cisplatin. A VIhP regimen.

Twenty-one patients with refractory germ cell tumors were treated with a chemotherapy regimen containing etoposide (VP-16) (V) 75 mg/m2/day (days 1 to 5), ifosfamide (I) 3 g/m2/day (days 1 and 2) with a 3.6 g/m2 continuous infusion of mesna (days 1 and 2), and high-dose cisplatin (hP) 40 mg/m2/day (days 1 to 5). The regimen is referred to as VIhP. Nineteen patients were evaluable for response. Five patients (26%) achieved a complete remission (CR) with chemotherapy alone, and three patients (16%) were in CR after resection of a residual nonactive tumoral mass (e.g., necrosis and/or fibrosis and/or mature teratoma). Thus, a CR rate of 42% was achieved with the entire treatment. One additional patient achieved a CR after resection of active, bulky disease. Among the responders, five patients (26%) are still alive and disease-free at 6, 7, 9, 10, and 18 months after the initiation of the chemotherapy. However, toxicity was heavy in this protocol. Severe myelosuppression was observed with 10 patients developing aplasia and six patients documented sepsis. Reversible Grade 1-2 renal toxicity occurred in 14 patients, and Grade 2-3 peripheral neurotoxicity occurred in six patients. No hemorrhagic cystitis was encountered. We conclude that a VIhP regimen seems to play an active role in refractory germ cell tumors although the presence of high-dose cisplatin in this regimen does not appear to improve the response rate compared to that of a conventional dose. Toxicity, which seems to be enhanced, is currently under detailed study. However, the contribution of VIhP as a first-line treatment in poor prognosis, advanced germ cell tumors warrants further study.

Adolescent↗
PubMed1988

Risk factors for candidemia in cancer patients: a case-control study.

Risk factors for candidemia were analyzed in a case-control study of 30 cancer patients with candidemia and 58 controls. In a univariate analysis, previous surgery, neutropenia, central catheterization, chemotherapy, specific antibiotic treatments, and peripheral cultures positive for Candida spp. were associated with a significantly increased risk of candidemia. In a multivariate logistic model, the significant risk factors for candidemia were positive peripheral cultures for Candida spp. (P = 0.02), central catheterization (P = 0.03), and neutropenia (P = 0.05). These results should help to identify cancer patients with a high risk of candidemia, who should be given early systemic antifungal therapy.

Adult↗
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↗
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

Blood cell kinetics and total body irradiation.

The early response of blood cells to irradiation has been studied in leukemia patients who received total body irradiation (TBI) prior to cyclophosphamide and bone marrow transplantation. After a single session treatment (10 Gy in 4 h) the most dramatic variation was observed in the granulocytes. At the end of the irradiation their concentration was 2 to 6 times higher. Because of a subsequent rapid decline, the peak may be overlooked if the blood counts are delayed. Lymphocytes decreased to 50% at the end of the single session TBI and continue to decrease exponentially, with a half time of 30 h. During a fractionated irradiation (11 X 1.2 Gy in 4 days) the lymphocyte number dropped to 60%, 13 h after the first fraction and this decline continued with a half time of 30 h during the treatment. From the data obtained in vivo, a lymphocyte D0 value of 1.2 Gy was computed. The lymphocyte subsets (B.T. OKT4 OKT8) did not exhibit different radiosensitivities either in vivo or in vitro. The disappearance of lethally hit lymphocytes from the blood exhibits a biphasic kinetic: 50% of the cells disappear in a few hours and 50% with a half time at 30 h. Lymphocytes irradiated either in vitro or in vivo when in culture disappear slowly, contrasting with the in vivo findings. It may suggest that lethally hit lymphocytes are quickly removed from the circulating pool in vivo.

Blood Cell Count↗
PubMed1987

[Specific anti-cytomegalovirus immunoglobulins in the prevention of cytomegalovirus infections in bone marrow allografts].

In order to assess the role of specific anti-CMV immunoglobulins in the prevention of severe cytomegalovirus infection in bone marrow transplant recipients, 46 consecutive patients were treated from day 1 to day 90 with injection of hyperimmune immunoglobulin with titres greater than 10,000 (ELISA) prepared from plasma selected for its high antibody titre (greater than 1,250). None of the patients developed CMV interstitial pneumonia; 5 patients developed diffuse pneumonitis, 2 of the aspergillus type and 3 apparently idiopathic, which progressed to fibrosis. There were no deaths directly attributable to CMV infection. This study confirms the efficacy of high dose immunoglobulin therapy in the high risk period for the prevention of sever CMV infection. In the absence of effective antiviral therapy, it is important to use all measures of prevention in patients with bone marrow transplants. The double identification of seronegative and hyperimmune blood donors allows preparation of uncontaminated cell fractions (with respect to CMV) and the selection of hyperimmune plasmas for the preparation of specific immunoglobulins.

Adolescent↗
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↗
PubMed1985

Phase-I-II study of high-dose melphalan and autologous marrow transplantation in adult patients with poor-risk non-Hodgkin's lymphomas.

Eleven adult patients with poor-risk non-Hodgkin's lymphoma were treated with high-dose melphalan (140 mg/m2) or high-dose combination chemotherapy (BCNU, Ara-C, vindesine and melphalan) followed by autologous bone marrow transplantation. Six of the eight patients evaluable for response achieved complete remission and one achieved partial remission. Response duration ranged from 1.5 to 12 months (median 2 months). Prompt hematological recovery occurred in all patients. The duration of aplasia and the extrahematological toxicity were similar in both groups. High-dose melphalan alone or associated with other drugs followed by marrow infusion appears to produce a high response rate and demonstrates the potential for salvaging patients with refractory lymphoma.

Adult↗
PubMed1983

Assessment of viral and immune factors in EMC virus-induced diabetes: effects of cyclosporin A and interferon.

EMC virus-induced diabetes in mice may be a model of human type I diabetes. It is postulated that auto-immune reaction plays a role in beta cell destruction after viral aggression. The use of anti-viral (interferon) or immunosuppressive drugs (Cyclosporin A) could contribute to an understanding of the pathogenesis of diabetes in this model. Early or late administration of cyclosporin A increased mortality and frequency of diabetes in female mice and did not influence these parameters in males despite a reduction of pancreatic inflammatory lesions. Interferon administered at the time of virus inoculation diminished mortality in both sexes and frequency of diabetes in males. These results are against an autoimmune pathogenesis for diabetes in this model and suggest that the virus plays the major role in beta cell damage.

Animals↗
PubMedDate not supplied

rIL-2 in metastatic soft tissue sarcomas refractory to chemotherapy: response and enhancement of further chemosensitivity.

Chemotherapy (CT) in advanced and metastatic soft tissue sarcoma (STS) has a reported response rate of 17 to 30%, with a median survival of 30 months. Experimental and clinical studies have demonstrated some response with high-dose intravenous recombinant Interleukin-2 (r-IL2). We report a retrospective analysis of twelve patients with metastatic or locally evolutive STS who received high-dose rIL-2 immunotherapy: all patients were pre-treated with CT and were non responsive. All of these patients developed usual severe toxicity. One patient achieved a partial response with rIL-2 with more than 75% regression of lung metastases. All patients received CT post rIL-2 and 2 of them achieved a further response: 1 of them had a complete response (CR), and one had a partial response (PR). These results suggest that rIL-2 has a relatively low efficacy in patients with STS but that some of these patients can be, after rIL-2, responders to CT despite previous resistance.

Adult↗