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Biomedical subjects

F Beaujean

Publications and source records attributed to F Beaujean.

At least 19 recordsLinked to original sources
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↗
PubMed1991

A simple, efficient washing procedure for cryopreserved human hematopoietic stem cells prior to reinfusion.

We describe our experience with a washing procedure used on cryopreserved, thawed bone marrow (BM) and peripheral blood stem cell (PBSC) grafts prior to autologous transplantation in 50 and 12 patients respectively. The procedure consists of a stepwise dilution with 2% human serum albumin and centrifugation performed either manually or using a blood cell processor (Cobe 2991). In vitro studies showed mean recoveries of 80.8% for BM nucleated cells and 73.9% for BM hematopoietic progenitors (CFU-GM). The corresponding recoveries for PBSC were 89.1 and 93.9%. After 4 h storage at +20 degrees C of the manipulated grafts, no significant loss of CFU-GM was observed. We conclude that the technique is simple and efficient for washing large numbers of hematopoietic stem cells. This method may avoid the clinical complications often arising with unwashed grafts.

Blood Cells↗
PubMed1990

Rapid technique for cryopreservation of Echinococcus multilocularis metacestodes.

Cysts of E. multilocularis were minced to prepare a crude homogenate and after addition of glycerol at a final concentration of 10%, cryopreservation was performed at a rate of 1 degree C min-1 in a controlled-rate freezer. The aliquots were subsequently stored in liquid nitrogen. All 22 isolates tested were successfully cryopreserved and their viability maintained.

Animals↗
PubMed1990

Enhanced in vitro cytotoxicity of 1,3-bis-(2-chloroethyl)-1-nitrosourea or buthionine sulfoximine combined with a reactive oxygen-generating enzyme immunotoxin.

The glutathione inhibitor drugs, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and buthionine sulfoximine (BSO), were tested in vitro in order to assess their cytotoxic effectiveness when combined with an enzyme immunotoxin (eIT) composed of a T-cell reactive monoclonal antibody (mAb) 097 coupled to the reactive oxygen-generating enzyme, glucose oxidase (GO) (EC 1.1.3.4). As targets of this eIT we used mature human T-cells or leukemia cells that expressed the 097 epitope. We found that treatment of the cells with subtoxic amounts of mixtures of both a drug and the 097 eIT markedly potentiated cytotoxicity compared to either drug or eIT alone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[New valvular homografts. Prospects and limits of their viability. Report of 42 implantations].

The regain of interest in aortic homograft bioprostheses is related to the prospects of improved viability resulting from explanation from organ donors, preservation in rich tissue culture media, together with the progress made in techniques of cryopreservation. Viability studies examining morphology of electron microscopy and tests of tissue culture confirm this notion of longer viability. These properties raise hopes of satisfactory long-term results while acknowledging outstanding antigenic problems which require strict A-B-O system compatibility. The results of a preliminary series of 42 valve homografts implanted at Henri Mondor Hospital over the last 5 years are reported. Twenty-one bioprostheses were implanted on the right side in congenital heart disease with good results in every case. Twenty-one were implanted in the aortic position in children and show no signs of degeneration as yet. One poor result was related to a technical error in calibration. The rebirth of this technique raises certain hopes, especially in aortic valve replacement.

Adolescent↗
PubMed1990

[Value of high-dose chemotherapy followed by bone marrow autograft in non-seminomatous germinal tumor with poor prognosis. Results of the combination of cisplatinum, etoposide and cyclophosphamide (PEC protocol)].

In recent years, the prognosis of non-seminomatous germ-cell tumors has been greatly improved by the use of novel chemotherapeutic regimens including platinum derivatives. However, the prognosis remains poor for a certain proportion of these patients. We have therefore developed an intensive chemotherapy protocol (PEC) followed by bone marrow autografting: cisplatin (40 mg/m2/day x 5 d), etoposide (350 mg/m2/day x 5 d), cyclophosphamide (1,600 mg/m2/day x 4 d). Forty-four poor-prognosis patients were thus treated. The results can be stratified into 3 categories, as follows: I: 12 refractory patients: 3 CR, 6 PR, 2 failures, 1 unevaluable. Median survival was short (7 months, range 2-16 months); II: 6 patients with sensitive relapse: 5 CR, 1 unevaluable. Four patients remained in CR at 42, 45, 46 and 48 months; III: 26 patients who received PEC as consolidation therapy in the first CR-PR after courses of conventional chemotherapy and who were selected at the time of diagnosis on the basis of factors of poor prognosis: 16 CR, 3 PR, 7 unevaluable. Two-year disease-free survival (Kaplan-Meier) is 60%. The median duration of neutropenia (less than 0.5 x 10(9)/l) was 15 d (range 6-37) and that of thrombocytopenia (less than 20 x 10(9)/l), 13 d (range 3-32). The most significant non-hematologic toxicity was of the gastrointestinal tract; in particular severe mucositis. Four iatrogenic deaths occurred (2 candidiasis, 1 aspergillosis and 1 hemorrhage). Pharmacokinetic studies were used to determine the optimum time for reinfusing the marrow and provided information on the mechanism of the mucositis. In conclusion, PEC protocol showed a high efficacy with 94% response rate (68.5% CR) among the 35 evaluable pts. Patients refractory to conventional treatment did not appear to benefit from this intensive chemotherapy. However, it appears that it may be useful for patients with relapses sensitive to salvage therapy. Encouraging results were obtained with the PEC protocol administered as early consolidation for patients with identifiable risk factors at diagnosis. A multicenter, randomized trial is currently underway in France to compare this approach with standard conventional chemotherapy.

Adolescent↗
PubMed1990

[Viability of new valvular homografts. An evaluation at the Henri Mondor Hospital].

The renewed interest in valvular homograft is due to the new concept of their viability. This viability requires procurement from organ donors and preparation in rich tissue culture medium immediately prior to cryopreservation. This viability, confirmed by morphological tests especially electron microscopy, and by cell culture tests is the basis for satisfactory long-term results. Antigenic aspects justify rigorous respect of A-B-O compatibility. A preliminary clinical series of 35 valvular homografts (16 on the right side and 19 in the aortic position), implanted especially in children over the last five years at the Henri Mondor Hospital, is reported here, No tissue failures have been reported to date.

Aortic Valve↗
PubMed1990

[Role of high-dose chemotherapy followed by bone marrow autograft in the treatment of metastatic Ewing's sarcoma in children].

Thirty-two children were treated for metastatic Ewing sarcoma by high-dose chemotherapy followed by autologous bone marrow transplantation. Fourteen patients entered phase II studies of high-dose alkylating agents. The response rate observed was 61%. High-dose chemotherapy was used as consolidation in complete remission of 18 patients. Disease free survival appears to be better than that observed under conventional altered chemotherapy. However, with only 4/18 long term survivors, these results remain unsatisfactory, taking into account the recent encouraging results of semi-continuous conventional chemotherapy.

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

Hemopoietic reconstitution after repeated autologous transplantation with mafosfamide-purged marrow.

Twenty-nine children (median age: 41 months) with advanced solid tumors received, as consolidation therapy, two consecutive courses of high-dose chemotherapy (HDC) followed by mafosfamide-purged autologous marrow transplantation (ABMT) with a 3- to 4-month interval between each course. The malignancies were neuroblastoma (n = 22), Ewing's sarcoma (n = 5) and rhabdomyosarcoma (n = 2). Patients received a preparatory regimen consisting of combined high-dose melphalan before each ABMT, with the exception of five patients who received busulfan and cyclophosphamide before the second ABMT. Prior to HDC, bone marrow sufficient for two transplantations was harvested in remission, treated with mafosfamide (50 micrograms/ml) and cryopreserved. Following incubation with the drug, a consistent inhibition (greater than 99%) of granulocyte and macrophage colony-forming units was observed. Despite the elimination of measurable hematopoietic progenitors, all patients underwent engraftment within a similar period of time after the first and the second ABMT. However, peripheral leukocyte and granulocyte recovery was delayed (median 26 and 28 days, respectively, after the first graft; median 27 and 28 days after the second graft). No difference was observed in the bacterial infections following the first and second ABMT. One patient died after the second transplant with diffuse aspergillosis. Recovery to 50 x 10(9) platelets/l occurred after a median 42 days (range 19-71) after the first ABMT and 43 days (range 14-110) after the second. Two patients died of recurrent disease before attaining a normal platelet level. One patient remained thrombocytopenic and died from visceral failure at day 200. These results demonstrate the feasibility of repeated ABMT with mafosfamide-treated marrow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

In vitro chemical eradication of small cell lung cancer: application in autologous bone marrow transplantation.

Autologous bone marrow transplantation raises the question of the possible reinjection of tumour cells together with marrow. This paper investigates the ability of chemical compounds other than cyclophosphamide derivatives to eradicate small cell lung cancer (SCLC) in bone marrow. The responsiveness of SCLC lines to cis-platinum, doxorubicin, VP16, Celiptium (an ellipticine derivative), Ditercalinium, a new drug belonging to the pyridocarbazole series, and Asta Z were measured in an agar-agar clonogenic assay. Cis-platinum and Ditercalinium exhibited a high tumouricidal effect. The low cloning efficiencies of SCLC lines in an agar-agar clonogenic assay did not allow tumour cells to be detected among bone marrow cells with sufficient sensitivity. Therefore cis-platinum and Ditercalinium were tested on bone marrow-tumour cell mixtures cultured in a liquid medium allowing the detection of one tumour cell per 10(4) bone marrow cells. As cis-platinum exhibited a low myelotoxicity, it is proposed for purging bone marrows of patients with SCLC.

Antineoplastic Agents↗
PubMed1988

Nonbacterial nonfungal interstitial pneumonitis following autologous bone marrow transplantation in children treated with high-dose chemotherapy without total-body irradiation.

Between February 1979 and May 1986, 165 children were treated with autologous bone marrow transplantation after high-dose chemotherapy without total-body irradiation for a hematologic malignancy or a solid tumor. Nonbacterial nonfungal interstitial pneumonitis was observed in 24 children and was the cause of death in 11 cases. Of the 24 cases of interstitial pneumonitis, 14 were considered to be idiopathic. Cytomegalovirus was the major pathogenic agent detected in the 10 other cases of interstitial pneumonitis (n = 5), followed by Herpes zoster (n = 2), Pneumocystis carinii (n = 1), tumor (n = 1), and adenovirus (n = 1). The only factor found to correlate significantly with the increased rate of interstitial pneumonitis was the use of high-dose 1-3 bis chloroethyl-1 nitrosourea (BCNU) (600 mg/m2), whereas BCNU at a dose of 300 mg/m2 did not affect this rate. These data, when compared with the literature, show a lower incidence of interstitial pneumonitis than in allogeneic transplantations, and an incidence similar to that observed in syngeneic transplantations, although there was no radiation toxicity in this series.

Adenovirus Infections, Human↗
PubMed1988

[Metastatic neuroblastoma: consolidation treatment with 2 courses of high-dose chemotherapy followed by a bone marrow autograft].

Among 62 children over 1 year of age at diagnosis who were treated for stage IV neuroblastoma, 33 entered remission after conventional therapy. They received high-dose chemotherapy and in vitro purged bone marrow transplantation as consolidation therapy. Fifteen patients received one course and 18 two courses. At present, 16/33 grafted patients are alive in CR with a median follow-up of 28 months. Toxicity of this regimen was tolerable. Under this treatment, actuarial disease free survival is improved compared with that observed under conventional therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Effects of irradiation on human platelets stored at 20 degrees C.

The morphologic and functional properties of platelets after irradiation with 2500 rads and storage, in first-generation containers, for 48 h in a liquid phase at 20 degrees C with continuous horizontal agitation have been analyzed and compared with a control group of the same platelets which were not irradiated. The preservation technique induced changes in the morphology and aggregation stimulated by ADP and collagen. However, no significant differences were found between the irradiated and non-irradiated groups. Irradiation is not a conditioning factor to add to the hazards of preserving platelets in a liquid phase.

Adenosine Diphosphate↗