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Biomedical subjects

M Flesch

Publications and source records attributed to M Flesch.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1989

Pyoderma gangrenosum in an allogeneic bone marrow transplant recipient.

We present the case of a 15-year-old boy who developed facial pyoderma gangrenosum following an allogeneic bone marrow transplantation for the treatment of a 'blast' crisis developing in the course of chronic myelogenous leukaemia. The lesion appeared 7 months before any evidence of relapse. The discussion is focused on both the presentation of pyoderma gangrenosum associated with myelo-proliferative disorders and its pathogenesis via the underlying immunosuppression.

Adolescent↗
PubMed1989

Allogeneic bone marrow transplantation in patients with multiple myeloma.

50 patients with a median age of 41 years (range 29-54) underwent allogenic bone marrow transplantation for multiple myeloma. 35 patients were on second-line treatment, and 15 on first-line treatment. 24 patients were considered refractory to previous treatment. 45 patients received marrow from HLA-matched sibling donors (3 of these from twin donors), and 5 from unrelated or related non-sibling donors. 21 patients entered complete remission, while 15 had persistent disease following repopulation of the marrow. 14 patients were not evaluable for remission status because of early transplantation-related death. The overall median survival from bone marrow transplantation was 27 months, with a projected long-term survival of 34%. Patients who were 40 yr of age or older had a survival that was not different from that of patients between 29 and 40 yr of age. The median disease-free survival of patients who entered complete remissions was 41 months. These patients tended to have a longer survival than patients with persistent disease following repopulation of the marrow. Allogeneic bone marrow transplantation appears to be a promising method for treatment of certain patients with multiple myeloma.

Adult↗
PubMed1988

Marrow transplantation from HLA non-identical family donors for the treatment of leukaemia: a pilot study of 15 patients using additional immunosuppression and T-cell depletion.

Fifteen patients with high-risk leukaemia were given T-cell depleted marrow transplants from HLA non-identical related donors. They were treated with a combination of total body irradiation (TBI), high-dose cytosine arabinoside (Ara-C) and high-dose melphalan in an attempt to prevent a host-versus-graft reaction. Antilymphocyte globulins were given prior to transplantation for additional immunosuppression to 13 patients and in-vivo monoclonal antibody anti-human LFA1 to two. Engraftment and chimaerism assessed by HLA typing were achieved in 14 patients. Seven developed acute graft-versus-host disease (two fatal), one failed to engraft. Six patients died in complete remission from cytomegalovirus (CMV) interstitial pneumonitis and three remain alive in complete remission 2, 3 and 13 months after transplant. We conclude that aggressive immunosuppression allows for sustained engraftment of T-cell depleted HLA non-identical marrow. The incidence and severity of GVHD are acceptable and CMV pneumonitis remains the major problem.

Adolescent↗
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↗
PubMed1987

Bone marrow transplantation in multiple myeloma: report from the European Cooperative Group for Bone Marrow Transplantation.

Of 14 patients who received an allogeneic bone marrow graft from HLA-compatible sibling donors, 10 have survived for 6 to 34 months posttransplantation (median, 12 months). Four patients have died, two of relapse at extramedullary sites, one of severe acute GVHD, and one from GI bleeding and pericardial effusion. One patient is alive in relapse and four patients have signs of minimal persistent disease. Five patients are well without signs of active disease. Minor improvement in osteolytic lesions on X-ray were seen in three patients, but the X-ray bone structure was mainly unchanged in most patients. Bone marrow transplantation appears promising for treatment of certain patients with multiple myeloma.

Adult↗
PubMed1987

[Mammary localization of malignant non-Hodgkin's lymphomas. Apropos of 4 cases].

Mammary localizations of non-hodgkinian malignant lymphomas (NHML) are rare. They occur in three different contexts: isolated tumor of the primary mammary lymphoma, initial "first manifestation" tumor of a diffuse lymphomatous disease, or else a mammary tumor occurring during the course of a known NHML. Four cases of mammary localization of NHML are reported. A review of the literature permits to bring out the following characteristics: probable etiological role of pregnancy, clinical picture of one or several masses, uni or bilateral, evoluting rapidly, and frequently associated to inflammatory signs; false benign aspect on mammograms. Histological examination associated with a strict evaluation of the extension is fundamental in order to determine therapy and prognosis. These two factors have been considerably modified in the past two decades as it is the case for all NHML. Chemotherapy occupies an essential place in the treatment. Mammary localization of NHML is first of all a lymphomatous disease, which is often a diffuse disease before becoming a breast disease.

Adult↗
PubMed1986

[Allogenic bone marrow grafts in acute myeloid leukemias. A retrospective study in 111 grafted patients in first complete remission].

Between 1978 and 1984, in 13 French Transplant Centers, 111 patients with acute myelogenous leukaemia underwent allogeneic bone marrow transplantation while in first complete remission. The conditioning regimen consisted of cytoxan 60 mg/kg X 2 and 10 Gy total body irradiation. To prevent graft-versus-host disease, 75% of the patients were given methotrexate and 25%, cyclosporine A. The probability of remaining in complete remission was 61% at 5 years. The probability of survival was 43% at 5 years, with a plateau between 2.5 and 6 years. The most frequent causes of death were interstitial pneumonia, relapses and graft-versus-host disease. Relapses were more frequent in cases with M 4-5 cytology than in those with M1 to M3 cytology (P less than 0.01). Transplant-related deaths were mainly consecutive to graft-versus-host disease and its facilitating effect on pneumonia (P less than 0.05). These results indicate that bone marrow transplantation can cure a large proportion of patients with acute myelogenous leukaemia, especially AML subtypes without monocytic differentiation. Improvements in conditioning regimens for the M 4-5 subtypes and in prevention of graft-versus-host reaction and cytomegalovirus infection should give rise to further developments in this field.

Adolescent↗