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E Racadot

Publications and source records attributed to E Racadot.

At least 91 records · Page 5Linked to original sources
PubMed1987

Prevention of graft-versus-host disease in HLA-matched bone marrow transplantation for malignant diseases: a multicentric study of 62 patients using 3-pan-T monoclonal antibodies and rabbit complement.

In order to evaluate the effectiveness and reproducibility of T cell depletion in human leukocyte antigen (HLA)-matched bone marrow graft to prevent graft-v-host disease (GVHD), our multicentric study (nine different centers) investigated 62 consecutive patients with poor prognosis leukemia or hematosarcoma from June 1984 to November 1985. The data were updated October 1, 1986, and the mean follow-up was 18 +/- 4.3 months. T cells were depleted with a combination of 3-pan-T cell monoclonal antibodies (CD2 "D66"; CD5 "A50"; CD7 "I21") with a single incubation of rabbit complement (C'). The average number of T cells infused was 0.66 X 10(6) +/- 0.56/kg body weight. Twenty-six patients received chemoprophylaxis for GVHD, 16 received methotrexate, and ten received cyclosporin A. Only a single case of severe (greater than grade II) GVHD was observed, yet the incidence of graft failure was 19%. Factors that might have influenced the occurrence of graft failure appear to be the lack of radiotherapy in the conditioning regimen; the conditioning regimen itself (fractionated total body irradiation [TBI], 12 Gy, v single dose is better than TBI, 10 Gy, but still not statistically significant); and the age of the patients (high-risk after 30 years of age). In contrast, neither the number of nucleated cells reinfused nor the level of T cell depletion (provided the T cells were below critical numbers) seemed to have an influence, nor did chemoprophylaxis for GVHD or splenectomy in chronic granulocytic leukemia (CGL) patients. The survival of graft failure patients was very poor (one of 11; survival at 15 months of the initial graft). Thus, our study demonstrates the reproducibility and high effectiveness in preventing GVHD by immunodepletion of T cells in a large-scale multicentric assay, in which compliance with the protocol of immunodepletion was reasonably good. This study thus provides interesting clues to overcoming graft rejection.

Adolescent↗
PubMed1987

Successful graft-versus-host disease prevention without graft failure in 32 HLA-identical allogeneic bone marrow transplantations with marrow depleted of T cells by monoclonal antibodies and complement.

Thirty-two patients with acute leukemia, chronic granulocytic leukemia, or multiple myeloma received a T lymphocyte-depleted HLA-identical marrow. After being treated with pan-T monoclonal antibodies (MoAbs) and one round of baby rabbit complement, the mean percentage of T cell depletion was 94% +/- 4%. The number of residual viable T cell infused to the patient was 0.99 +/- 0.65 X 10(6) per kg body weight. The patients were conditioned with fractionated total body irradiation (TBI) (12 Gy) preceding high doses of cyclophosphamide (120 mg/kg). Methotrexate was used as an additional immunosuppressant in the first ten patients. For the following 22 patients no posttransplant immunoprophylaxis was administered. Eight patients died within three months due to complications related to transplantation. Engraftment was achieved in all evaluable patients, and no patient has a late graft failure. The proof of total chimerism was established in 24 patients. Twenty-four of 27 evaluable patients (88%) did not have an acute graft-v-host disease (GVHD) greater than grade 0 to 1. Two patients had a grade 2 (skin only), and one patient had a grade 4 acute GVHD (the latter had only 80% of T cell depletion). A medullary relapse occurred in 11 patients (nine of them had previously been defined as "high risk leukemia"). Our data suggest that it may not be necessary to deplete nearly all T cells to prevent acute GVHD in recipients of HLA-identical marrow.

Adolescent↗
PubMed1986

Autologous bone marrow transplantation (ABMT) for acute leukaemia in complete remission: a pilot study of 33 cases.

Thirty-three leukaemic patients in CR were treated by high-dose therapy followed by ABMT: 18 of them had acute non-lymphoblastic leukaemia (ANLL) in first remission (CR1) with a mean age of 23.7 years (3-44). All but one of them were conditioned with a polychemotherapy regimen including 6-thioguanine, Ara-C, CCNU, and cyclophosphamide. The marrow cells were purged by chemical means in 16 cases. Five transplant-related deaths were observed: three cardiac failures, one interstitial pneumonitis and one aspergillus pneumonia. At the time of analysis (October 1984), four patients had relapsed and eight were still in unmaintained CR1 (44+, 46+, 30+, and five between 2.5+ and 8+ months post transplant). Fifteen patients had acute lymphoblastic leukaemia: four were autografted in CR1 and 11 children were grafted in CR2; the conditioning regimen was fractionated total body irradiation followed by cyclophosphamide for all but one patient who was conditioned with BACT (Burkitt leukaemia); the marrow was purged by a chemical agent in 11 patients and by monoclonal antibodies and C' in four: four out of 15 patients relapsed (two grafted in CR1 and two grafted in CR2); 10 patients are still in unmaintained CR: two adults grafted in CR1 (26+; 12+ months) and eight children with a mean follow-up of 13.4 months post graft (2 + -45+ months). The clinical study leads to the following conclusions: in adult patients the marrow should be harvested during CR1 and at the time of minimal residual disease. The quality of previous chemotherapy and conditioning regimen prior to ABMT play a prominent role in the in vivo eradication of the leukaemic cells. The real impact of marrow purging is still unknown and a larger series of homogeneous patients, conditioned with the same protocols and the same transplant timing, is required before any conclusions can be drawn.

Acute Disease↗
PubMed1985

[Epidemiologic characteristics of 21 peranesthetic anaphylactoid accidents observed in a population of 12,855 surgically treated patients].

A study of anaphylactoid reactions (AR) observed between September 1982 and September 1983 was carried out in the surgical departments of a French regional hospital. The patients who had presented clinical symptoms suggesting an AR (bronchospasm, collapse, tachycardia, with or without skin rash) during a general anaesthesia were included in this study. A precise history of previous anaesthesias and allergy was taken; allergological testing was carried out six to eight weeks after the AR. It included intradermal skin tests (ST) and a human basophil degranulation test (HBDT) with the suspected drugs. Out of 12,855 patients operated on under general anaesthesia in the hospital, 21 AR were seen during the year under study, in 18 women and 3 men, of median age 27 years (extreme values: 11 and 62). The median number of previous anaesthesias was 2 (extreme values: 0--in 4 cases- and 22). Cardiocirculatory abnormalities were the most frequent clinical symptoms of the AR: they consisted of decreased arterial pressure in 13 cases, with 8 cases of vascular collapse. Respiratory symptoms were less frequent but severe bronchospasm was observed in 5 cases. Skin rashes were seen simultaneously in 13 out of the 21 observations. A history of allergy was found in 11 patients. Total IgE serum concentration averaged 134 kU X 1(-1) (extreme values: 32-378). Results of histamine-sensitivity skin tests were not significantly different from those observed in a control group. Calcemia and magnesemia were in the normal range. One to four drugs were tested in each patient: 41 tests combining ST and HBDT were carried out.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Removal of marrow T cells with OKT3-OKT11 monoclonal antibodies and complement to prevent acute graft-versus-host disease. A pilot study in ten patients.

We studied the feasibility of T cell depletion of bone marrow for transplantation in preventing acute graft-versus-host disease GVHD in patients having a high risk of acute GVHD. We report our preliminary clinical experience of the ex-vivo treatment of allogeneic marrow using a pan-T monoclonal antibody combination (OKT3-OKT11) plus baby rabbit complement. Ten patients received allografts from HLA-identical sibling donors. All patients had malignant hematological disease with poor prognosis (6 acute leukemia, 3 chronic granulocytic leukemia, and 1 multiple myeloma). Nine patients were at high risk of acute GVHD (older than 30 years for 4 patients, chronic granulocytic leukemia in acute or accelerated phase for 3, and acute leukemia in relapse for 2). Posttransplant management with methotrexate was maintained until day 100 in the first four patients and stopped at day 11 for the six others. The ex-vivo treatment with the OKT combination and complement removed 88.3% +/- 11.8 of the T lymphocytes. The myeloid progenitors recovered at the end of the procedure showed a moderate effect of monoclonal antibodies and complement (75.8% +/- 12.2). Engraftment was achieved in all patients: 23.3 days +/- 5.10 to reach 0.5 X 10(9) granulocytes per liter and 31.5 days +/- 12.2 to reach 50 X 10(9) platelets per liter. No acute GVHD was observed in this group of patients. Of the 10 patients, 7 are alive and well and have been in continuous remission from 2-10 months. Three patients have relapsed.

Adolescent↗
PubMed1985

[Phenotype of periparasitic hepatic infiltrating mononuclear cell in human alveolar echinococcosis].

Phenotypic analysis with monoclonal antibodies showed that OKT8+ T cells represent the main cell population of the periparasitic mononuclear cell infiltrate in the liver of 7 patients with alveolar echinococcosis. A significant decrease of the OKT8+ subpopulation had been previously demonstrated in the peripheral blood mononuclear cells of these patients. The results obtained in this study suggest an intrahepatic homing for these particular T cells. However, functional analysis of these cells is required in order to assess the physiopathological significance of these observations.

Antibodies, Monoclonal↗
PubMedDate not supplied

Induction of tissue factor expression on human umbilical vein endothelial cells by cell-specific HLA class I antibody: preliminary data.

Donor-specific antibodies may play an important role in the development of chronic allograft rejection process. However, the mechanisms leading to intimal vascular proliferation and fibrosis remain poorly understood. The aim of this study was to examine whether donor-specific HLA antibodies induce overexpression of tissue factor (TF) by endothelial cells. HLA typed human umbilical vein endothelial cells (HUVEC) were incubated for 1 to 12 hours with LPS (10 microg/mL), and increasing concentrations (1 to 500 microg/mL) of anti-HLA A1 antibody specific for an antigen expressed by HUVEC and of an anti-HLA A2 antibody for which A2 was not expressed by the HUVEC. Expression of TF mRNA transcripts was quantified using real time Q-RT PCR and TF activity was tested in cell lysates of cultured HUVEC using a chromogenic TF activity assay. HUVEC-specific anti-HLA A1 antibody at low concentrations (10 microg/mL) induced both a significant increase of TF mRNA transcripts after 1 hour of incubation and TF activity after 3 hours incubation compared to incubation with medium alone or with the nonspecific anti-HLA A2 antibody (n = 4 for all experiments, P < .05). These data show for the first time that specific anti-HLA antibody can induce overexpression of TF on endothelial cells. TF, a transmembrane glycoprotein involved not only in the onset of the coagulation cascade, but also in cell proliferation and anti-apoptotic processes, may play a role in the development of alloantibody-induced chronic rejection.

Endothelium, Vascular↗
PubMedDate not supplied

Immunological follow-up of 17 patients with rheumatoid arthritis treated in vivo with an anti-T CD4+ monoclonal antibody (B-F5)

Seventeen patients with steroid-refractory rheumatoid arthritis were treated with a monoclonal antibody: anti-T CD4/B-F5 (IgG1) for 10 days. The daily dose was 20 mg. No severe side effects were observed and clinical improvement was seen in 15 patients, accompanied by a steep decline in C reactive protein levels. This improvement persisted as long as 12 months in 3 patients. A decline in lymphocyte counts was observed 2 hours after infusion. CD3+, CD4+, CD8+ and B cells were affected. Monocyte levels also decreased, whereas NK cell levels remained unchanged. After 24 hours a subsequent recovery of lymphocyte cell numbers made it possible to return to pre-treatment levels. Residual CD4+ cells coated with CD4 antibody were sporadically found even if residual antibody could be detected in the serum. These results indicate insufficient mAb concentrations. No patients developed detectable anti-mouse Ig antibodies during the treatment period, but 5 patients developed antibodies 15 to 30 days after the end of the treatment. Proliferative responses (mainly the response to ConA) were reduced at the end of the treatment. One month later the proliferative response returned to pre-treatment levels. mAb treatment did not induce long lasting cell activation, as indicated by the low levels of CD25+ or DR+ cells. Soluble IL2 receptor levels were significantly higher before treatment, but did not change after treatment. Soluble CD8 and soluble CD4 molecules were also more numerous before treatment and this increase was correlated with clinical parameters. Of interest was the correlation between the variations in soluble CD8 and the Ritchie index during treatment. The increased levels of serum TNF alpha and IL6 were not modified by treatment. A randomized study now appears necessary to prove the efficacy of the treatment. Such a study would also provide biological data and thus help to define factors predictive of a response in this heterogeneous disease.

Adult↗
PubMedDate not supplied

Monoclonal antibodies in human organ transplantation and auto-immune diseases.

The usefulness of monoclonal antibodies (mAbs) in the transplantation field has become evident over the last couple of years. Different mAbs have been used as a prophylactic treatment after transplantation, in a therapeutic way against acute organ rejection and new diagnostic tools to predict clinical rejection immerge. One can even hope that with humanised mAbs or human mAbs obtained by repertoire cloning the formation of human anti-mouse antibodies will be solved although on the one hand this appeared not to be a big problem and on the other hand anti-idiotypic antibodies can still be expected. However, the most puzzling question is how the mAbs modulates the immuno-response and this not only in organ rejection but also in auto-immune diseases. Only one out of many CD25 mAbs with seemingly similar epitope recognition can be used in therapeutical treatment of acute Graft versus Host Disease. The same mAb is not, however, very efficient in the prophylactic treatment of kidney transplantation without association of suboptimal doses of cyclosporin A. Another example is a CD4 mAb which is efficient in the treatment of polyarthritis with no side effects but which provokes transient but clear side effects when used in psoriasis or multiple sclerosis patients. A second CD4 mAb with high inhibitory activity in several bioassays compared to the first CD4 mAb has no beneficial effect at all on polyarthritis. Also the question why there is a percentage of "no response" patients among apparently identical "good response" patients remains unanswered. However it becomes clear from these experiences that: 1) mAbs recognizing a similar epitope and being of the same isotype will not automatically have the same effect in therapy. 2) side effects may be depending of the disease treated. 3) the activities of mAbs in bioassays and even animal models very often do not reflect the in vivo situation in human. 4) efficiency of the treatment with mAbs can be increased by a better understanding of the mode of action and increased efficiency can be expected by association of several mAb or mAb with drugs for the "no response" patients and should be the next step in the therapeutical use of mAbs.

Animals↗
PubMedDate not supplied

Soluble IL-2-receptor and CD8 in the serum and the periparasitic granuloma of patients with alveolar echinococcosis.

Cellular immunity plays a key role in the defence against the larva of the cestode Echinococcus multilocularis. This larva is responsible for alveolar echinococcosis (AE) of the liver, a rare parasitic disease which occurs in endemic areas including European alpine countries, Alaska, the USSR, Western China and Northern Japan. We have shown a marked decrease of the CD8+ T-cell population in the blood and we have described an infiltrate composed mainly of activated CD8+ T-cells in the liver lesions of most patients with AE. In this study, we assessed the serum level of soluble IL-2-receptor (sIL-2R) and CD8 (sCD8) in 37 patients (23 men, 14 women, mean age 59.5 yrs) with a histologically proven AE. The results, obtained using sandwich ELISA, were compared to those of healthy controls and correlated to parameters evaluating the severity of the disease. The mean serum levels of sIL-2R were significantly higher in AE patients than in controls. There was a significant correlation between sIL-2R levels and both the volume of parasitic lesions and a calculated index of severity of the disease. The mean serum levels of sCD8 did not differ significantly from the values obtained in controls. These results indicate that the infiltration of the liver by CD8+ T-lymphocytes is not associated with an increased release of sCD8 into the serum. The circulating levels of sIL-2R appear to reflect the extent as well as the severity of the disease. Immunostaining of the cells of the periparasitic granuloma suggests that the cell origin of the sIL-2R could be macrophages rather than T-lymphocytes.

Adult↗
PubMedDate not supplied

[Autograft of bone marrow following intensive treatment in acute lymphoid leukemia in children].

Ten children were autografted for ALL in second complete remission (CR). The conditioning regimen consisted of cyclophosphamide (60 mg/kg/day X 2) and total body irradiation (10 to 13.2 grays). It was well tolerated, no deaths occurred during the first 3 months post-graft. Nine children remained in second CR, without any maintenance therapy, from 2 to 40 months after ABMT and the median survival time was 11 months. One child died 112 days post-graft, following a cerebral hemorrhage (thrombocytopenia less than 10 X 10(9) platelets/liter). One girl, affected by B ALL, was autografted while in first CR after intensive chemotherapy (modified BACT) 5 months after diagnosis. She relapsed 8 months later. Seven bone marrows have been purged ex vivo by chemotherapy (ASTA-Z) and 3 by anti-CALLA monoclonal antibodies and complement.

Adolescent↗
PubMedDate not supplied

[Open therapeutic trial of anti-T CD4 monoclonal antibody in multiple sclerosis].

Twenty-one patients with active multiple sclerosis (16 progressive and 5 recurrent forms) were treated with murine monoclonal anti-T CD4/BF5 antibodies in an open trial. Tolerance was relatively good; 11 patients had side effects including facial swellings, skin eruptions and trembling which occurred only at the first infusion. Treatment had to be stopped in one female patient. Nine months after initiating treatment, no relapse had occurred in any of the 5 patients with a recurrent form and improvement was observed in 3 patients with a progressive form. At the end of the treatment period, there was a clear drop in the number of CD3+ cells and particularly in CD4+ cells, a decrease which was less after one month. All the patients who had side effects showed an increased level of serum IL6 and alpha TNF. These findings demonstrate that this type of long-term treatment is possible in patients with multiple sclerosis and suggest that in another trial it would be important to evaluate the effect in recurrent forms.

Adult↗