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Biomedical subjects

E Racadot

Publications and source records attributed to E Racadot.

At least 55 records · Page 3Linked to original sources
PubMed1993

Treatment of multiple sclerosis with anti-CD4 monoclonal antibody. A preliminary report on B-F5 in 21 patients.

Twenty-one patients with definite active multiple sclerosis (MS) were treated with a monoclonal anti-T CD4/B-F5 (murine IgG1) antibody for 10 days. Side effects were observed in 11 patients during the first infusion. These side effects were accompanied by and probably related to a transient increase in IL6 and TNF alpha serum levels. This problem led to treatment interruption in one patient. Neither clinical improvement nor deterioration was observed in the course of treatment. EDSS improvement (> 1 point) occurred in six patients one month post-treatment. One month after the end of treatment total lymphocytes and CD3+ and CD4+ cells were significantly decreased. Cytokine analysis performed in serum and in CSF before and after treatment showed no induced modifications. Ten patients developed xenogenic antibodies. It is of interest that the patients with relapsing-remitting forms were relapse-free at the 6th month post-therapy.

Adult↗
PubMed1993

Immunological characteristics of umbilical cord blood cells: phenotypic and functional analysis.

The purpose of this study was to phenotype and assay immunological function on cord blood from 70 samples. Immunophenotyping indicated similar numbers of CD2, 3, and 8-positive cells as in adult bone marrow. CD4-positive cells were increased and CD19, 20, and CD56-positive cells were decreased in numbers. Proliferative responses to nonspecific mitogens were lower in cord blood cells than in adult cells, as was NK activity and spontaneous secretion of IL-6 and TNF-alpha. This study confirms the relative immaturity of cord blood cells even when some functional assays appear normal.

Adult↗
PubMed1993

Graft failure after T cell depleted HLA identical allogeneic bone marrow transplantation: risk factors in leukemic patients.

In a retrospective analysis of T cell depleted bone marrow transplantation, we have looked at different parameters in order to determine risk-factors of graft-failure after allogeneic bone marrow transplantation for leukemia. Fifty-one patients with acute leukemia or chronic myeloid leukemia have been analysed. For 33 of them, the pretransplant conditioning regimen consisted of fractionated total body irradiation (TBI) at 12 Gy prior to cyclophosphamide (120 mg/kg). The other patients received various reinforced preparative regimens. T-cell depletion consisted of treating marrow cells with pan-T monoclonal antibodies (CD2+CD3 or CD2-CD5-CD7) followed by complement mediated cytolysis. No post-transplant immunosuppressive prophylaxis was administered except for the first nine patients who received Methotrexate alone. In this group of 51 patients, 12 died within 3 months from graft-related complications and 10 developed graft failure (no engraftment or rejection). Among the possible risk factors associated with this failure, two graft-related parameters appeared significant: the number of CFU-GM progenitors and the number of viable T cells injected with the marrow inoculum. No correlation with graft failure was found with other parameters including diagnosis, disease status at transplant, conditioning regimen, age, sex, and CMV status of donor/host pairs. However, the interpretation must remain cautious because of the relatively small samples in each group.

Adolescent↗
PubMed1993

A CD2+ subset of non-malignant peripheral blood lymphocytes from patients with Sézary syndromes overexpress the low-molecular-weight GTP-binding protein Rab2.

The Rab branch of the Ras-related GTP/GDP-binding proteins currently includes at least 25 related members which are involved in the intracellular vesicular transport along the secretory and endocytic pathways in eukaryotic cells. The overexpression of the Rab2 protein in peripheral mononuclear cells is demonstrated from 13 out of 17 patients exhibiting a Sézary syndrome. Moreover, this phenomenon is detectable in other lymphoid and myeloid malignancies. Several lines of evidence are shown suggesting that the Rab2 overexpression can be related not to leukemic cells but to a subset of peripheral lymphocytes with a CD2+ phenotype. Our results provides strong evidence for the implication of a small GDP/GTP-binding protein in immunological events associated with neoplastic states. The precise cellular population involved in this process remains to be determined.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1993

Treatment of severe rheumatoid arthritis by anti-interleukin 6 monoclonal antibody.

Interleukin 6 (IL-6) appears to be a potential mediator of inflammation that may contribute to the pathogenesis of joint inflammation in RA. Anti-IL-6 monoclonal antibodies (Mab) may represent a new tool in RA treatment. Five patients with RA, after previous anti-CD4 therapy (B-F5) without antimouse immunization were included in our open pilot study. The anti-IL-6 Mab (B-E8, IgG1) was given intravenously (10 mg/day) for 10 consecutive days in hospital. No side effects were noted. Clinical and biological (C-reactive protein) improvement appeared during the treatment period. However improvement was transitory (mean: 2 months). Unexpectedly serum IL-6 levels increased in 4 patients with this treatment that seemed to have antiinflammatory effects. Further studies are required to evaluate the real benefit and the mode of action of this Mab.

Antibodies, Monoclonal↗
PubMed1992

[Monoclonal antibodies in the treatment of rheumatoid arthritis].

Monoclonal antibodies (MoAb's) make it possible to treat rheumatoid arthritis with selective immunotherapy. These antibodies may be directed against various targets, such as lymphocyte activation antigens, cytokines or subpopulations of lymphocytes (notably TCD4 +), involved in the pathogenesis of the disease. Recent open studies have demonstrated the feasibility and safety of this therapeutic method, but the number of patients who entered the trials is still low, and the clinical, biological and immunological results vary considerably in importance and duration, without remission. No response predictive factor could be elicited from these studies. The murine origin of these MoAb's exposes to the frequent risk of immunization which may interfere with the effectiveness and safety of a second treatment. Some possibilities can already be envisaged, including potentiation of the MoAb by coupling with a cytotoxic agent (anti-CD5 + ricin) and "humanization" of murine MoAb's (chimeric anti-CD4) reducing the risk of immunization. Further (controlled) trials therefore are indispensable to evaluate the true rank occupied by this therapeutic method in rheumatoid arthritis.

Antibodies, Monoclonal↗
PubMed1992

Phase I-II trial of a monoclonal anti-tumor necrosis factor alpha antibody for the treatment of refractory severe acute graft-versus-host disease.

In a multicenter pilot study, 19 patients with severe acute graft-versus-host disease (aGVHD) refractory to conventional therapy and serotherapy with a monoclonal anti-interleukin-2 receptor antibody were treated by in vivo infusion of a monoclonal anti-tumor necrosis factor alpha (TNF alpha) antibody (B-C7). Ten patients were grafted from a genotypically identical sibling, five from an HLA-mismatched family member, and four from an HLA-matched unrelated donor. Before B-C7 treatment, 15 patients had grade IV and four had grade III GVHD. In all cases, patients received cyclosporine/methotrexate as aGVHD prophylaxis. Patients were administered increasing doses of antibody (from 0.1 to 0.4 mg/kg). The antibody was infused in bolus daily for 4 days and then every other day twice (6 doses). No side effects were observed during treatment regardless of the dose level used. Changes in peripheral blood cell counts occurred in 8 of the 19 patients and appeared to be unrelated to B-C7. No truly complete response was observed; eight patients achieved a very good partial response (42.6%) and six a partial response (31.5%). The treatment was ineffective in five patients (26.4%). When present, the response occurred early (less than 3 days). In the 14 responding patients, gut lesions responded best (100%), followed by skin (85%) and liver (35.7%) lesions. In 9 of 11 evaluable patients (81%), GVHD recurred when treatment was discontinued in a median delay of 3 days (range, 2 to 120 days). All except one died from aGVHD. Two patients did not experience GVHD recurrence and are still alive 13 and 18 months post-bone marrow transplantation. This pilot study shows that a monoclonal anti-TNF alpha antibody may be of benefit to some patients with severe refractory aGVHD, but is ineffective to prevent GVHD recurrence in the majority of cases.

Acute Disease↗
PubMed1992

Interleukin-2-induced increase of a monoclonal B-cell lymphocytosis. A novel in vivo interleukin-2 effect?

A 56-year-old man with refractory B-cell lymphocytic non-Hodgkin's lymphoma was treated in a Phase II study with interleukin-2 (IL-2) (Roussel-Uclaf, Romainville, France). The patient had involvement of multiple lymph nodes and medullary and peripheral blood (3.6 x 10(9) monoclonal CD19-positive [CD19+] B-lymphocytes/l). After a 5-day cycle of IL-2 treatment, an eightfold increase of the monoclonal CD19+ population was observed (27 x 10(9) monoclonal CD19+ cells). The lymphocytosis decreased dramatically during the second cycle (days 15 to 19) of IL-2 treatment, resulting in 6 x 10(9)/l peripheral lymphocytes, with 5.5 x 10(9) B-lymphocytes. As soon as day 20, peripheral B-cells again increased considerably, with 32 x 10(9) CD19+ cells/l at day 27. The CD19+ population remained monoclonal as assessed by kappa/lambda cell-surface phenotyping and kappa gene rearrangement evaluation. Kinetics of the monoclonal B-lymphocyte response to IL-2 paralleled the natural killer/lymphokine-activated killer and T-cell response, with a 4-day latency period, suggesting an indirect enhancing effect of IL-2. Before and during IL-2 treatment, peripheral B-lymphocytes never expressed detectable levels of the p55 IL-2 receptor. However, the p75 IL-2 receptor was expressed significantly in the IL-2-responsive monoclonal B-cell population. Tumor necrosis factor alpha, a known (in vitro) B-cell tumor growth factor, reached high serum levels during IL-2 treatment. Response evaluation at day 45 showed stability of the lymph node involvement and the marrow lymphocyte infiltrate. At day 45, peripheral B-cell lymphocytosis was 7.5 x 10(9)/l. To the knowledge of the authors, this is the first report of an in vivo IL-2-induced reversible increase of peripheral monoclonal B-cell lymphocytosis.

B-Lymphocytes↗
PubMed1992

Treatment of rheumatoid arthritis with anti CD4 monoclonal antibody. Open study of 25 patients with the B-F5 clone.

Twenty-five defined severe RA patients (pts) (17 F, 8 M) were treated in an open study with a CD4 murine monoclonal antibody (Mab) (B-F5 clone, IgG1). Mab's daily dose was 10 mg (1 pt), 15 mg (2 pts), 20 mg (17 pts), 30 mg (4 pts) and 50 mg (1 pt) for 10 days. Tolerance was fair. Clinical improvement occurred during treatment period or within the first month in all but 2 patients, irrespective of Mab dosage. Improvement duration was variable (1 to 12 months), half of the patients still show signs of improvement at month 4. Biological parameters (CRP) improved parallel to the clinical. At day 180, 25% of the patients showed a reduction of 50% or more of the initial CRP values. There is no modification of RF titers, renal and hepatic parameters. Sequential evaluation showed a decrease of B, TCD3, CD4, CD8 lymphocytes and monocytes two hours after Mab infusion and return to baseline in 20 hours. Xenogenic immunization occurred in 6 patients without influence upon clinical response. These modifications are moderate and transient and do not account for the more prolonged effect in some cases, nor do they offer any prediction of further clinical response.

Adult↗
PubMed1992

[Soluble interleukin-2 receptor assay is unhelpful in chronic inflammatory rheumatism].

The level of soluble interleukin-2 receptors (SIL2-R), which reflects lymphocyte activation, is often described as a useful parameter for evaluating disease activity and progression in patients with inflammatory conditions. Serum SIL2-R was assayed using a sandwich ELISA method in 98 subjects including 38 controls (C), 36 patients with ankylosing spondylarthropathy (AS) and 24 patients with rheumatoid arthritis (RA). SIL2-R levels were higher in RA patients than in controls and AS patients (p < 10(-4)), whereas the difference between AS patients and controls was small (p = 0.02). In RA patients, SIL2-R levels were not correlated with any of the clinical or biological parameters studied and remained unchanged during clinical improvements. In the AS group, SIL2-R levels showed no correlations with inflammation parameters (CRP, IgA) and was similar in patients with and without HLA B27 or appendicular joint involvement. This study failed to provide any evidence that SIL2-R levels are helpful for monitoring patients with inflammatory joint disease.

Adult↗
PubMed1992

Transplantation of umbilical cord blood in neuroblastoma.

It has been shown that umbilical cord blood contains concentrations of hematopoietic progenitor cells equal to those of normal adult bone marrow. We successfully performed transplantation of cord blood combined with a hematopoietic growth factor (rGM-CSF) in a seven year old child suffering from neuroblastoma. Cord blood cells were collected from an HLA identical sibling at the time of delivery and stored in liquid nitrogen. The patient was conditioned with busulfan 600 mg/m2 and cyclophosphamide 200 mg/kg before receiving the thawed cells. There were no immediate side effects. Hematological reconstitution occurred promptly (granulocytes greater than 0.5 x 10(9)/L on day 13, platelets greater than 30 x 10(9)/L on day 40), although at day 10 the child experienced acute grade II cortico-sensitive GvHD. Mixed hematopoietic chimerism was observed 2 months later and complete remission lasted for 8 months.

Child, Preschool↗
PubMed1991

Soluble CD8, IL-2 receptor, and tumor necrosis factor-alpha levels in steroid-resistant acute graft-versus-host disease. Relation with subsequent response to anti-IL-2 receptor monoclonal antibody treatment.

Serial determination of soluble CD8 (sCD8), soluble IL-2 receptors (sIL-2R), and tumor necrosis factor-alpha serum levels were performed in bone marrow transplant patients upon initiation, day 0 (D0) and at D10 of an anti-IL-2 receptor (alpha chain) monoclonal antibody (B-B10) in vivo treatment for steroid-resistant grade greater than or equal to 2 acute graft-versus-host disease (aGVHD). D0 and D10 sCD8 serum levels correlated strongly with response to B-B10 treatment (p = .003 and .001, respectively); 76% of the patients with D0 sCD8 levels less than 500 U/ml responded favorably to B-B10 treatment, versus only a 30% response if the sCD8 levels were greater than 500 U/ml (p = .02). Likewise, D0 tumor necrosis factor-alpha levels significantly correlated with subsequent response to B-B10 treatment (p = .03). D0 sIL-2R levels were not significantly different in B-B10-responsive and nonresponsive aGVHD patients. These results suggest that the serial determination of sCD8 and TNF serum levels could provide valuable predictive information as to steroid-resistant aGVHD responsiveness to anti-IL-2R treatment.

Adolescent↗
PubMed1991

Soluble interleukin-2 receptors in chronic renal failure.

A depression of the general immune response in uremia is well documented, and hemodialyzed (HD) patients present deficient interleukin-2 (IL2) secretion. Since soluble IL2 receptors (SIL2R) could affect the immune response through interaction with circulating immune cells, we studied the potential relationship between SIL2R concentration and lymphocyte subsets in 44 HD patients. HD patients present lymphopenia, higher CD4/CD8 ratio. CD16 counts and SIL2R concentrations than controls. A significant negative correlation was found between SIL2R concentration and lymphocyte count (p less than 0.01), and between SIL2R concentration and T4/T8 ratio (p less than 0.01). An increase of SIL2R concentration due to abnormal T cell preactivation in HD patients with nonreused cuprophan membranes could perhaps contribute to cell immunity impairment through IL2 binding and inhibition of T cell activation.

CD4-CD8 Ratio↗
PubMed1991

Therapeutic use of monoclonal anti-CD4 antibody in rheumatoid arthritis.

Ten patients with severe rheumatoid arthritis were treated with a murine monoclonal anti-CD4 (B-F5) antibody in an open study (one with 10 mg/day, 2 with 15 mg/day, 7 with 20 mg/day) for 10 consecutive days. Tolerance was excellent. All patients improved during treatment clinically (Ritchie's index, morning stiffness, pain scale) (p = 0.005), as well as biologically C-reactive protein (p = 0.008) with an average 60% reduction of each of these variables at Day 15, and clinical benefit lasted over 6 months in some patients. No significative depletion was noted in total lymphocyte or CD3, CD4, CD8, CD20, positive cells after treatment. Evidence of murine immunization was found in only 2 patients.

Aged↗