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Biomedical subjects

M Benbunan

Publications and source records attributed to M Benbunan.

At least 37 records · Page 2Linked to original sources
PubMed1996

Hematologic recovery and survival of lymphoma patients after autologous stem-cell transplantation: comparison of bone marrow and peripheral blood progenitor cells.

Autologous stem-cell transplantation is widely used as part of the treatment of poor prognosis lymphoma patients. Since 1986, peripheral blood progenitor cells (PBPC) mobilized by chemotherapy and/or hematopoietic growth factors have progressively been used instead of autologous bone marrow (BM) cells. Toxicity, engraftment and long-term outcome were compared in a population of relapsing or refractory lymphoma patients given high-dose therapy. During 1986 to 1993, 150 patients with refractory or relapsed non-Hodgkin's lymphomas (n = 93) or Hodgkin's disease (n = 57) received intensive therapy followed by the reinjection of BM (n = 72) or PBPC (n = 78). PBPC were collected by aphereses during the phase of hematologic recovery after mobilization by chemotherapy alone (n = 36) or associated with GCSF (n = 43). Conditioning regimens included chemotherapy alone in 77%, associated with total body irradiation (TBI) in 23%. After stem-cell reinfusion, 55% of the PBPC group received GCSF versus 24% in the BM group. Results show that the median time to neutrophil counts > 500/microliters and platelets > 50,000/microliters was significantly shorter in the PBPC than the BM group, respectively 13 versus 23 days and 18 versus 26 days (P < 0.05). This difference remained significant (P < 0.05) when patients were stratified according to the administration or not of GCSF after transplantation. PBPC grafting after high-dose therapy was associated with a median reduction of the hospital stay of 10 days. The majority of patients (90%) maintained normal blood counts at 3 months, and no secondary graft failure was observed in either group. The use of TBI in the conditioning regimen was the only significant factor affecting long-term hematologic recovery. For relapsing patients with histologically aggressive lymphomas, overall survival and failure-free survival were similar in both groups. In conclusion, PBPC transplantation is a safe procedure associated with improvement of hematopoietic recovery and a shortened hospital stay.

Adolescent↗
PubMed1996

Transmission of hepatitis C virus in allografted patients: use of viral genotyping as an epidemiological marker.

One hundred and ninety-two allografted patients were tested for hepatitis C virus (HCV) RNA from 1992 to 1995 in Saint-Louis Hospital (Paris). They received blood products and intravenous immunoglobulins (IVIG) and more particularly Gammagard IVIG suspected of transmitting HCV (batches distributed in France between January 1993 and February 1994). The presence of serum HCV RNA was tested by polymerase chain reaction (PCR) in 86 patients who received Gammagard IVIG during the critical period and in 106 patients treated with IVIG other than the suspected batches of Gammagard (negative controls). HCV RNA positive sera were HCV genotyped. Ten out of 86 patients who received Gammagard IVIG during the exposed period vs 0 out of 106 negative controls were HCV RNA positive showing a higher prevalence of HCV infection in the exposed patients that in the negative controls (P = 0.001). The link between HCV transmission and IVIG infusion was reinforced by the high frequency of genotype 2b (70%) in the exposed patients because genotype 2b is an underrepresented subtype in France (< 1%).

Biomarkers↗
PubMed1995

Granzyme B and perforin lytic proteins are expressed in CD34+ peripheral blood progenitor cells mobilized by chemotherapy and granulocyte colony-stimulating factor.

Granzyme B and perforin are cytoplasmic granule-associated proteins used by cytotoxic T lymphocytes and natural killer (NK) cells to kill their targets. However, granzyme B gene expression has also been detected in a non-cytotoxic hematopoietic murine multipotent stem cell line, FDCP-Mix. The objective of the present study was to investigate whether granzyme B and perforin could be expressed in human hematopoietic CD34+ cells and if present, discover what their physiologic relevance could be. The primitive CD34+ human cell line KG1a was investigated first and was found to express granzyme B and perforin. Highly purified hematopoietic stem/progenitor cells were then selected using the CD34 surface antigen as marker. Steady-state bone marrow (BM) CD34+ cells did not contain these proteins. Peripheral blood (PB) CD34+ cells, which had been induced to circulate, were also analyzed. After chemotherapy (CT) and granulocyte colony-stimulating factor (G-CSF) treatment, CD34+ cells strongly expressed mRNAs and proteins of granzyme B and perforin. In contrast, CD34+ cells mobilized by G-CSF alone were negative. Western blot analysis further showed that granzyme B and perforin proteins were identical in CD34+ cells and activated PBLs. Such proteins might be implicated in the highly efficient migration of CD34+ stem/progenitor cells from BM to PB after CT and G-CSF treatment. The cellular adhesion mechanisms involved in the BM homing of CD34+ cells are disrupted at least temporarily after CT. The Asp-ase proteolytic activity of granzyme B on extracellular matrix proteins could be used by progenitor cells for their rapid detachment from BM stromal cells and perforin might facilitate their migration across the endothelial cell barrier.

Antigens, CD34↗
PubMed1994

Production of a new murine monoclonal antibody with Fy6 specificity and characterization of the immunopurified N-glycosylated Duffy-active molecule.

A murine monoclonal antibody (mAb i3A; IgG1, kappa light chain) was obtained using human red blood cells as immunogen. The antibody showed Fy6 specificity since it agglutinated all but Fy(a-b-)-untreated red cells and failed to agglutinate chymotrypsin-treated cells. An erythrocyte membrane protein of 42-46 kD was revealed as the major component recognized by the antibody on immunoblots. The antibody also bound to 92- to 95- and 200-kD proteins, tentatively identified as oligomers of the 42- to 46-kD monomeric form. The affinity-purified Fy6-active protein was converted to a sharp band of 35 kD after N-glycanase treatment. The molecule appeared as a slightly broadly band after neuraminidase treatment but was not further altered by O-glycanase. The i3A mAb bound to 6,000 +/- 1,000 receptor sites on either Fy(a-b+), Fy (a+b+) and Fy(a+b-) red cells with an affinity constant in the range of 3-6 x 10(8) M-1. No binding was observed to other blood cells nor to several cells (B, T, myelomonocytic and erythro-leukemia cell lines). Also, the bulk of i3A-Fy6 immune complexes could be dissociated from the red cell membrane with as low as 0.2% Triton X-100, showing that the Fy6-active glycoprotein is not tightly associated with the membrane skeleton. Our data obtained with a new monoclonal antibody directed to the Fy6 antigen demonstrate that the blood group Duffy-active component is a red cell-specific glycoprotein carrying one or more N-linked oligosaccharides.

Animals↗
PubMed1994

Comparison of autografting using mobilized peripheral blood stem cells with and without granulocyte colony-stimulating factor in malignant lymphomas.

Peripheral blood is becoming widely used as the only source of hematopoietic stem cells to support marrow ablative therapy in advanced lymphoma. We report data from 23 patients with high risk non-Hodgkin's (n = 19) and Hodgkin's lymphoma (n = 4) who underwent high-dose therapy with mobilized peripheral blood stem cell (PBSC) autografting. Peripheral blood progenitors were recruited using cytotoxic chemotherapy followed by administration of recombinant human G-CSF (filgrastim 5 micrograms/kg/day). Myeloablative treatment with autologous PBSC support was administrated to the 23 patients and followed by G-CSF at the same dose after cell reinjection. Hematopoietic reconstitution was compared with a control group of lymphoma patients who received chemotherapy mobilized PBSC transplantation but without G-CSF prior to leukaphereses or after high-dose therapy. The median time to neutrophil recovery > 0.5 x 10(9)/l was significantly shorter in study patients compared with the control patients (10 days and 17 days respectively) (p < 0.05). Self sustaining platelet counts of > 50 x 10(9)/l occurred at a median time of 17 days in both groups. Stable hemopoietic reconstitution was seen with a follow-up of 6 months after PBSC transplantation. In addition, a significant relationship was observed between the number of CFU-GM infused and the time to platelet recovery. We confirm the effectiveness of G-CSF given prior to PBSC harvesting in generating high numbers of progenitor cells. Hematologic recovery following high-dose therapy was improved after PBSC rescue and G-CSF.

Adolescent↗
PubMed1994

Fresh frozen plasma: plasma secured and virus inactivated plasma.

Two procedures are now used in France to reduce the risk of viral transmission by blood plasma transfusion: either a quarantine method or a chemical method based on solvent-detergent technic. Since August 4th, 1992, a chemical virus inactivated blood plasma product from the Bordeaux blood bank has been authorized.

Blood Component Transfusion↗
PubMed1992

The role of autologous blood stem cells in support of high-dose therapy for multiple myeloma.

During the last few years, high-dose therapy with hemopoietic stem cell support has become a well-admitted therapeutic option for young patients with MM. The role of allogeneic or autologous graft and of blood rather than bone marrow as the source of hemopoietic stem cells must be further investigated. Autologous PBSC transplantation has, however, both practical and theoretic advantages over allogeneic and autologous BMT: (1) It can be applied to most patients, especially if blood stem cells are collected early in the course of therapy. (2) It usually induces relatively rapid hematologic reconstitution. (3) In comparison with autologous BMT, it appears to minimize the hazard of the reinfusion of malignant cells.

Combined Modality Therapy↗
PubMed1992

Hematopoietic progenitors cells in cord blood.

Human umbilical cord blood was evaluated as an alternative to bone marrow as a source of stem cells for hematopoietic transplantation. In order to define an optimal collection procedure, we have studied the parameters that influence the collection, handling and storage of cord blood. We have attempted to correlate the quality of the samples with obstetrical and neonatal parameters. Using culture techniques we have studied the long term viability of the cells. Cell separation was also investigated. Our results suggest that most of the sample collected could be suitable for transplantation, in term of progenitors. However the observed variability between samples suggest that an efficient control of the quality of the samples is important.

Blood Banks↗
PubMed1992

Clinical applications of stem cell transfusion from cord blood and rationale for cord blood banking.

Umbilical cord blood collected and cryopreserved at birth contains enough hematopoietic progenitor stem cells for engraftment. HLA identical sibling cord blood transplant has been performed for the first time, in a child with Fanconi anemia. Three years latter, this child is alive with a complete donor type bone marrow. Since this first attempt, several other patients with other diseases have been transplanted successfully. Cord blood banking is a safe and easy procedure. Due to the high proliferative capacity of neonatal hematopoietic progenitors and to the relative immunological functional immaturity of neonatal lymphocytes cord blood cells could be used for matched unrelated or partially mismatched transplants.

Adult↗
PubMed1991

High dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma.

We report the results of peripheral blood stem cell (PBSC) collection performed after priming with a semi-intensive CHOP regimen in 70 patients with aggressive multiple myeloma (MM). Forty-one of the 44 previously untreated patients compared to 17 of the 26 patients with a refractory disease yielded stem cells enough for autotransplantation. Phenotypic and genotypic studies of collected mononuclear cells, even performed after depletion of monocytes and/or of T lymphocytes, did not reveal contamination by tumor plasma cells or clonal B cell precursors in any studied case. Forty-eight of the 58 patients with successful PBSC collection have been presently treated by high dose therapy followed by autologous blood stem cell transplantation (ABSCT). Among the 43 patients who received a regimen including total body irradiation, four died within six months after the autograft. All remainders responded and most often achieved an impressive tumor mass reduction. Ten relapsed and four died from disease progression. Nine to 70 months (median: 35 months) after blood stem cell collection, 29 patients are either in apparent complete remission or with a state of stable residual disease, most often minimal. Blood stem cell autograft was successful in all evaluable patients and the kinetic of hematologic recovery was roughly related to the amount of reinfused CFU-GM (2.1 to 50 x 10(4)/kg). Median delays for granulocytes greater than 500/mm3 and platelets greater than 25,000/mm3 were 15 days and 20 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗