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Biomedical subjects

M Benbunan

Publications and source records attributed to M Benbunan.

At least 55 records · Page 3Linked to original sources

Serological characterization of murine monoclonal antibodies directed against acquired B red cells.

Balb/c mice were immunized with acquired B red cells. Twelve clones specific for acquired B red cells were obtained from two fusions. A detailed investigation of three clones is reported here. These antibodies appear to be directed to the B-like epitope since they are inhibited by galactosamine and fail to react after acetylation of red cells. E 231 is an example of a series of antibodies closely specific for acquired B red cells which can be useful in elucidating some AB0 typing problems. E 167 and F 47 showed a cross-reactivity with A1 red cells and a synthetic A trisaccharide. No affinity for B antigen could be demonstrated for any of the antibodies.

ABO Blood-Group System↗

Hematopoietic stem cell potential from umbilical cord blood.

We studied the conditions of collection and isolation of hematopoietic cells from cord blood in order to optimise the sampling. A statistically significant correlation was found between the total stem cell content of the samples and the time of delivery suggesting that the quantity of hematopoietic stem cells available is higher when cord blood collection is performed earlier during pregnancy. Attempt to isolate the white cells resulted in a dramatic loss of stem cells. Factors affecting cell recovery and purification must be investigated in order to optimize cord blood cell banking.

Blood Specimen Collection↗

Treatment of severe cytomegalovirus infection with ganciclovir and high-dose intravenous immunoglobulin in patients with allogeneic bone marrow transplants. A pilot study.

Cytomegalovirus (CMV) infection is the leading infectious cause of death after bone marrow transplantation (BMT) because of the high mortality rate associated with CMV pneumonia. However, very interresting results were recently reported when treating CMV penumonia with the combination of ganciclovir and high doses of intravenous anti-CMV immunoglobulin. In order to achieve an even better therapeutic efficacy, we have conducted a pilot study consisting of early administration of the combination therapy, as soon as CMV was isolated from the material obtained by bronchoalveolar lavage (BAL). A BAL was performed when symptoms of severe CMV infection were present and sometimes also systematically when an asymptomatic CMV viremia was diagnosed. Out of 18 BMT patients with CMV isolated from BAL in the absence of pulmonary signs, 9 became long-term survivors without any episode of CMV pneumonia and 9 died. However, only 2 patients died because of CMV pneumonia. Early treatment with the combination of ganciclovir and anti CMV immunoglobulin seems thus to decrease the incidence of CMV pneumonia (2/18) as it is known that about half of the untreated patients with CMV viremia will develop CMV pneumonia. We have also used the combination therapy to treat 3 cases of CMV pneumonia. As 2 patients survived the CMV pneumonia episode, this confirms the possible effectiveness of the combination therapy for the treatment of established CMV pneumonia. However, our pilot study points out the usefulness of an early treatment. At such an early stage, application of the combination therapy could affect the intensity and length of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗

Human CD3 gamma delta + activated lymphocytes exhibit killer activity in vitro against autologous leukemic cells.

TCR gamma delta expressing T cell clones are able to exhibit in vitro strong cytolytic activity against cultured tumor cell lines as the myeloid K562 or the Burkitt's lymphoma Daudi cell line. We investigate the possibility of developing TCR gamma delta bearing T cell lines from peripheral blood of 2 leukemic patients in complete remission in order to study their ability to kill autologous leukemic cells. T lymphocyte clones are obtained by limiting dilution of lymphocytes from the blood of patients with an acute lymphoblastic leukemia (ALL). The T cell clones are first selected for their CD8- CD4-phenotype and then for their ability to react with the monoclonal antibody anti-CD3 without presenting reactivity with a monoclonal antibody directed against the TCR alpha beta. Further biochemical studies have indicated that the CD3 associated structure expressed on the cell membrane of these T cell clones is a gamma delta heterodimer. Functional analysis have indicated that these cloned cells are able to kill in a classical cell mediated lysis assay the autologous leukemic cells only when also LAK activity is observed. Thanks to this clonal expansion 10(10) cells/week indefinitely only 1 sample of peripheral blood will be necessary. Would these results be found with other leukemic patients, we propose to use this procedure for a possible application of killer cells for maintenance therapy of leukemia.

Antigens, Differentiation, T-Lymphocyte↗

Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft.

Eight patients with stage III aggressive multiple myeloma, refractory to current chemotherapy in six cases, were treated by high-dose chemotherapy (nitrosourea, etoposide, and melphalan) (HDC) and total body irradiation (TBI), followed by autografting with blood stem cells. These cells were previously collected by leukapheresis performed during hematologic recovery following cytotoxic drug-induced bone marrow aplasia. Seven patients were alive 9 to 17 months after HDC-TBI and graft. One died at day 40 from cerebral bleeding. All living patients achieved a 90% or greater reduction in tumor mass. In two cases, a complete remission (CR) has persisted at a follow-up of 15 and 16 months. Three patients have been well and off therapy with stable minimal residual disease (RD) since 10, 11, and 17 months, respectively. A patient in apparent CR and another with RD have relapsed 9 to 12 months posttreatment. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. These results, although still preliminary, indicate that HDC and TBI, followed by blood stem cells autograft, which has both practical and theoretical interest over allogeneic or autologous bone marrow transplantation, deserve consideration in selected patients with multiple myeloma.

Adult↗

Treatment of multiple myeloma by high dose chemotherapy, total body irradiation and autologous blood stem cell autograft.

Fourteen patients with stage III aggressive multiple myeloma were treated by high dose chemotherapy (carmustine, etoposide and melphalan) and total body irradiation. This procedure was followed by autografting using blood stem cells previously collected by leukapheresis performed during recovery of cytotoxic drug-induced bone marrow aplasia. One patient died from cerebral bleeding at day 40. All other patients, including 9 whose disease was refractory to conventional treatments, achieved an impressive tumor mass reduction (over 90% in 12 cases). Two patients relapsed and died 12 and 15 months after the graft; another one relapsed but is still alive at 24 months. Two to 23 months (median 12 months) after the autograft, 10 patients are well either in apparent complete remission (2 cases) or with a state of stable minimal residual disease. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in the 13 evaluable patients. The cells collected by leukapheresis were studied for clonal Ig genes rearrangements indicative of circulating tumoral cells (or clonal B precursors) and none were found. Although preliminary, these results appear promising and high dose chemotherapy followed by autologous blood stem cell graft deserves consideration in young patients with multiple myeloma.

Adult↗

Increased resistance to non-MHC-restricted cytotoxicity related to HLA A, B expression. Direct demonstration using beta 2-microglobulin-transfected Daudi cells.

Experiments in several laboratories have shown that target susceptibility to NK and lymphokine-activated killer (LAK) cytotoxicity is inversely correlated with the target expression of HLA Class I molecules. We present the first direct evidence, obtained by gene transfection, that target cell HLA, A, B expression increases the resistance to the "so-called" non-MHC-restricted cytotoxicity. We have co-transfected, by electroporation, the human beta 2-microglobulin gene and the gene carrying the resistance to geneticin into Daudi cell line. Geneticin selection in culture followed by FACS sorting on the basis of strong positivity with the mAb W6/32 (which is specific for the HLA class I H chain associated to beta 2-microglobulin) have led to the establishment of a HLA+ Daudi cell line permanently expressing HLA A10, A11, and B17 molecules. Studies were performed in vitro to evaluate the susceptibility of these cells to either NK and LAK cytotoxicity. The HLA class I+ Daudi cells exhibit an increased resistance to killing by non-MHC-restricted killer cells (both NK and LAK) as compared with their HLA-Daudi counterpart.

Cytotoxicity, Immunologic↗

[Autografts of blood cells at various stages].

Thirty-nine patients with acute myeloblastic or lymphoblastic leukaemia had peripheral blood mononuclear cells collected by 3 continuous-flow leukapheresis as they entered first remission after induction chemotherapy. CFU-GM were assayed as a measure of the number of haemopoietic stem cells in each collection. Numbers of CFU-GM harvested varied among the patients (for example 0.27 to 155.10(4)/kg for ANLL patients). Nineteen patients underwent peripheral blood stem cells autografts after a conditioning regimen with high dose cyclophosphamide and TBI. The patients were transfused with a median of 2.2.10(4)/kg CFU-GM cells (0.28 to 100.10(4) CFU-GM/kg). Only 1 patient had a graft failure. The rate of haemopoietic recovery was studied for our patients and those reported in the literature. A strong correlation exists between the numbers of CFU-GM transfused and the rate of granulocytes and platelets recovery. Very rapid recovery are regularly obtained when the number of CFU-GM transfused is superior to 5.10(4)/kg.

Adult↗

[Blood samples programmed for deferred autologous transfusions --experience at the Hôpital Saint-Louis].

Since 1980 preoperative autologous blood donation program has been implemented at Hospital Saint-Louis involving 1,250 patients. This report describes the results from January to August 1987. A total of 131 patients undergoing 3 types of elective surgery (total hip replacement, plastic surgery, and bone marrow donation for allogenic transplantation) predeposited blood, donating on average 2.2 units of packed red cells. Nevertheless autologous red cell units represent only 2% of the total consumption in the Hospital Saint-Louis and 7% of the transfusions in the surgery patients. The use of predonated blood should be extended in order to reduce the incidence of transfusion-related disease.

Blood Transfusion, Autologous↗

Clinical and immunological restoration in patients with AIDS after marrow transplantation, using lymphocyte transfusions from the marrow donor.

The diagnosis of transfusion-associated acquired immunodeficiency syndrome (AIDS) was made in 2 patients who developed delayed opportunistic infections and severe cytopenias--56 months for the former (patient 1) and 22 months for the latter, (patient 2) following bone marrow transplantation (BMT) for aplastic anemia. In the third case, grafting for acute leukemia (patient 3) (HIV) infection was probably responsible for the failure of hematological and immunological reconstitution 8 months after allogeneic BMT. Each patient received 6 lymphocyte transfusions from the marrow donor for 3 weeks, combined with a 3-month course of low-dose recombinant alpha interferon. This treatment was followed by recombinant gamma interferon for 3 months. We showed that these 3 patients could resume a normal life for 9 months, at least, and that hematological restoration was observed. Our treatment succeeded in correcting the defect of proliferative response to Candida and the impairment of gamma interferon generation for 4 months in one patient and for more than 12 months in the other two recipients. Nevertheless T4 lymphocyte levels increased only slightly and HIV can still be isolated from the patients' blood. At the time of writing, patients 1 and 3 remain in good health with a partial immunological restoration while patient 2 has died of neurological impairment 2 years after the AIDS diagnosis. Although we cannot generalize this successful therapeutic approach to all patients with AIDS, the results may provide an interesting model of the potential effect of lymphocyte transfusions and the role of interferon therapy.

Acquired Immunodeficiency Syndrome↗

[HIV infections and transfusions].

The prevalence of AIDS now approaches 1% in patients with hemophilia and laboratory evidence of abnormal immunoregulation is found in 50% of patients with severe hemophilia. Current evidence indicates that a human retrovirus HIV/LAV is the etiologic agent which can be transmitted through the administration of blood products. We reported 7 cases in childhood, 5 acute leukemia, 1 metastatic neuroblastoma, and 1 severe aplastic anemia in whom AIDS occurred after administration of blood products. To date 5 patients are alive and 2 have died of infections. It is suggested that the use of steroids or antineoplastic agents increases the incidence of AIDS in patients infected with HIV/LAV because of altered immune suppression. The maintenance treatment is difficult in these patients. The widespread use of HIV serology to screen donated blood should help to prevent AIDS transmission in leukemic patients.

Acquired Immunodeficiency Syndrome↗

[Blood products].

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Blood Transfusion↗

[Induction therapy of acute leukemia in children. Current results and problems related to therapeutic aplasia. Apropos of 146 cases].

Between 1983 and 1984, 146 children have been treated in the pediatric hematology department of Saint-Louis Hospital (Paris) for induction of acute leukemia (AL). 119 had an acute lymphocytic leukemia (ALL) and 27 an acute non lymphocytic leukemia (ANLL). The rate of complete remission was 94% for all patients (97% in ALL and 81.5% in ANLL). Fever occurred in 95% of children with positive blood cultures in one third on these. Four children died between the fifth and the twenty fifth days after onset of treatment from sepsis. One of these patients was a neonate with ANLL. 127 patients had a central venous line during induction used for blood sampling and treatment (chemotherapy, antibiotics, parenteral nutrition, platelets and red blood cells infusions). This supportive care is very important to improve prognosis of the AL particularly in very intensive chemotherapy.

Acute Disease↗

Bone marrow transplantation for chronic granulocytic leukemia.

Thirty-seven patients with chronic granulocytic leukemia have been treated with supralethal chemoradiotherapy followed by transplantation of bone marrow from HLA-identical donors. All patients showed engraftment, and the Philadelphia chromosome (PH1) disappeared in each case. Four patients had syngeneic grafts before blast crisis and are still alive; 2 are in remission not maintained by therapy, and 2 others are receiving chemotherapy after having relapsed in the chronic phase. Thirty-three patients had allogeneic grafts; only 2 received the grafts during blast crisis, and neither is a long-term survivor. Of the 13 patients who had grafts in the accelerated phase, 6 died of complications related to the transplantation, and 1 died after a myeloblastic relapse. Thus 6 patients are in unmaintained remission with a median follow-up of 13 months. Eighteen patients received grafts in the chronic phase. All 10 survivors are in unmaintained remission with a median follow-up of 14 months; in this group, no patient has relapsed. The granulocytic hyperplasia of the chronic phase can be more effectively ablated than established blastic leukemia. The mortality rate of transplant-related complications must be weighted against the typical rate of progression of chronic granulocytic leukemia. Although a longer follow-up period is needed for full evaluation, bone marrow transplantation may now be offered to patients in the chronic phase in an attempt to achieve long-term survival or cure of more than one-half of these patients.

Adolescent↗