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Biomedical subjects

F Dreyfus

Publications and source records attributed to F Dreyfus.

At least 127 records · Page 7Linked to original sources

Donor bone marrow treatment with T101 Fab fragment-ricin A-chain immunotoxin prevents graft-versus-host disease.

Thirty-eight patients with haematological malignancies were treated with bone marrow transplantation using histocompatible immunotoxin T cell-depleted marrow siblings. All patients received conventional postgraft immunosuppression (methotrexate and/or cyclosporin A). Donor bone marrow was treated ex vivo with T101 Fab fragment coupled to ricin A-chain (T101 Fab-RTA) at a concentration of 10(-8) M of A-chain in association with NH4Cl (2 x 10(-2) M) in pH adjusted (7.8) incubation medium. A median cytoreduction of 99.5% (91-99.5) was obtained. The median of follow-up was 300 days. Only three patients developed grade II acute graft-versus-host disease (GVHD) (actuarial rate of acute GVHD: 9.1%). No chronic GVHD occurred. All patients but one engrafted. Six out of the 37 patients developed a documented bone marrow rejection (actuarial rate of graft failure: 18%). Ten patients relapsed (actuarial rate of relapse: 36.9%). These findings demonstrate that treatment of donor marrow with T101 Fab-RTA in association with NH4Cl at critical pH value can achieve a high level of mature T cell depletion and greatly reduce the incidence of bone marrow rejection and relapse after T cell-depleted allogeneic bone marrow transplantation.

Adolescent↗

Early involvement of the fim-2 and fim-3 regions in mouse myeloblastic leukemogenesis.

Retroviruses lacking oncogenes induce tumors or leukemias after a long latency which generally exceeds several months. Cellular transformation most probably results from the activation of cellular oncogenes or putative proto-oncogenes due to proviral integration. Several genetic changes are likely to be necessary for the appearance of fully malignant cells. However, the sequence of genetic changes initiating and leading to malignant transformation is difficult to study since, in most experimental conditions, the only accessible cells are fully transformed cells. We have previously described an in vitro model of murine myeloblastic leukemogenesis during which several successive steps leading to fully malignant and transplantable cells have been identified. This in vitro transformation process develops over approximately a 1-year period. In this paper, we demonstrate that frequent cellular DNA rearrangements due to proviral integrations in specific regions occur early in the myeloblastic transformation process and remain stable throughout the in vitro leukemogenesis, and in tumors derived from in vitro fully transformed myeloblasts.

Animals↗

Impact of T-cell depletion on outcome of allogeneic bone-marrow transplantation for standard-risk leukaemias.

71 leukaemic patients having HLA-matched bone-marrow transplants (BMT) were randomised to receive whole marrow (group A) or marrow depleted of T cells by treatment with monoclonal antibodies (anti CD4-CD5-CD8, group B; anti CD2-CD5-CD7, group C) plus complement. All patients received cyclophosphamide and total body irradiation before transplantation and cyclosporin after BMT. Marrow treatment removed 97% of T cells (median) in group B and 99% in group C. Although both serious and mild graft-versus-host disease (GVHD) were reduced in T-cell depleted patients, graft failure and relapse were increased. Graft failure was caused by GVHD and transplant complications in the controls and by rejection and relapse in the T-cell depleted groups; relapse-free survival did not differ between the groups. Without better control of host immunity and of the residual leukaemia T-cell depletion of the marrow, BMT should not be pursued in standard-risk patients.

Adolescent↗

Reconstitution of cytotoxic T lymphocyte activity following allogeneic bone marrow transplantation in man.

Longitudinal studies over an eight-month period have been performed to follow the T killer response restoration after allogeneic bone marrow transplantation (BMT). The capacity of the patient's peripheral blood mononuclear cells (PBM) to develop cytotoxic effector cells directed either against allogeneic cells or against Epstein-Barr virus (EBV) or Herpes-simplex virus-1 (HSV-1)-infected syngeneic cells was tested monthly. The data suggest that in most cases the cytotoxic T lymphocyte (CTL) activity, either allospecific or directed against EBV and the HSV-1 specific killer (HNK) responses, is quickly reconstituted in BMT patients. Roughly, these activities seem to be normal after two months following classic nondepleted grafting. However, in the two patients who had received a T-cell-depleted graft, the restoration was delayed. Furthermore, in the majority of the patients, once reconstituted the killer responses were relatively stable and the occurrence or absence of graft-versus-host diseases (GVHD) did not significantly modify these responses.

Adolescent↗

B cells from leukemic patients are relatively resistant to in-vitro EBV transformation.

Samples of peripheral blood mononuclear cells (PBMC) from normal donors or from leukemic patients were used to obtain Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL). Whereas the rate of transformation was around 85% with normal donors, it was only around 20% with leukemic patients. However no explanation for this resistance of B cells from leukemic patients to in-vitro EBV transformation could be found. Indeed no correlation exists between this EBV resistance and the age, sex, diagnosis or chemotherapeutic regimen. Furthermore no correlation is apparent between the percentage of B2+ cells, which should have EBV receptors, and the successful EBV transformation.

B-Lymphocytes↗

[Lymphomas and AIDS].

We report 21 cases of lymphomas associated with AIDS. Sixteen cases are Non Hodgkin's lymphomas of high grade malignancy. Immunoblastic B cell lymphomas are frequent: 11 cases/16, especially with extra nodal localisations. Three cases are Burkitt's lymphoma; 2 cases are large non cleaved cell lymphoma. Five cases of Hodgkin's disease are associated with AIDS related complex syndrome (ARC) showing the interest of lymph node biopsy in such patients. We analyzed 6 cases with lymphoid bone marrow infiltration and discuss the relationship between prelymphomatous states and low grade malignant lymphomas in AIDS or ARC patients.

Acquired Immunodeficiency Syndrome↗

[Colic carcinoma and basal cell epithelioma eleven years after Kaposi sarcoma with splenic and cutaneous involvement (author's transl)].

A case of Kaposi sarcoma (KS) with cutaneous and splenic involvement is reported. Carcinoma of the left colon and basal cell epithelioma arose eleven years after KS. Genetic, viral, and immunologic factors which may promote initiation and development of Kaposi sarcoma are reviewed. The responsibility of immunodeficiency, whether resulting from therapy or from other causes, in carcinogenesis is discussed. Prolonged survival may be seen after KS. Another primary malignant disease (lymphoma or solid tumor) may arise. The authors suggest that the risk of immunologic disorders, occurring spontaneously or induced by therapy, should be considered specifically for each patient with KS.

Adenocarcinoma↗

[Toxopachyosteosis of the tibial and fibular diaphyses (Weismann-Netter and Stuhl syndrome) (author's transl)].

Two cases of toxopachyosteosis involving the tibial and fibular diaphyses are reported. This rare condition, which is usually well tolerated, was first described by Weismann-Netter and Stuhl in 1954. This dysplasia affects both tibias and fibulas and usually results in symmetrical deformations. Characteristic features are anterior bowing of affected bones, with posterior thickening of the cortices. There are few clinical manifestations; small stature, often with delayed onset of walking. Biological investigations are negative. Roentgenograms often show embedding of the last lumbar vertebra with horizontalization of the sacrum. Scoliosis is a common finding.

Aged↗

[Meningeal carcinomatosis in adults (author's transl)].

Twenty cases of carcinomatous meningitis in adults, treated in the Gustave Roussy Institute between 1970 and 1980, are reviewed. In fourteen cases meningitis was secondary to breast cancer. Initial inflammation was present in 90% of the mammary tumors. Clinical features as well as biochemical and cytological findings in cerebrospinal fluid are described. The various therapeutic regimens using radiotherapy and intrathecal chemotherapy are analyzed in terms of survival and compared with other published studies. The most significant point is the necessity for early diagnosis which improves survival. However, prognosis for this metastatic disease is always very poor.

Adenocarcinoma↗