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Biomedical subjects

M Wiesneth

Publications and source records attributed to M Wiesneth.

68 records · Page 4Linked to original sources
PubMed1987

Evidence for the involvement of host-derived OKT8-positive T cells in the rejection of T-depleted, HLA-identical bone marrow grafts.

The recent introduction of a variety of techniques for removing T cells from bone marrow grafts has reduced the incidence of graft-versus-host disease (GVHD)-associated morbidity and mortality. Whether this advance will be translated into improved patient survival is unclear at present, mainly because these procedures increase the risk of graft failure. Since 1983 we have transplanted 25 consecutive leukemia patients with HLA-identical sibling grafts purged of T cells by a single incubation with the monoclonal antibody Campath-1 and donor complement. This approach was successful in reducing T cell contamination of the graft and preventing acute and chronic GVHD. In this group of patients two suffered irreversible graft failure and one developed reversible graft failure. In a similarly sized group of patients previously transplanted with unpurged marrow according to the Seattle protocol, no episodes of graft failure occurred. Since other causes of graft failure, such as drug toxicity or viral infections, could be largely excluded, this suggested that the graft failures were specifically related to the purging process. In haploidentical bone marrow transplantation (BMT) O'Reilly has identified residual host-versus-graft activity (HVG) as a cause of graft failure. The causes and mechanisms of graft failure in T-depleted HLA-identical sibling transplants have not been extensively investigated to date. In the three graft failures observed by us, the loss of the graft was preceded by the appearance of a population of activated lymphocytes. We have determined the phenotype and origin of this population and investigated its interactions with donor hemopoietic tissue in vitro.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Ex vivo T-cell depletion with the monoclonal antibody Campath-1 plus human complement effectively prevents acute graft-versus-host disease in allogeneic bone marrow transplantation.

We have developed a rapid and simple procedure for the elimination of mature T-cells from the donor marrow using a single incubation with the monoclonal antibody Campath-1 and donor complement. This resulted in a reduction of T-cell contamination to a mean of 1%. This regimen reduced the incidence of acute graft-versus-host disease significantly in 21 consecutive bone marrow grafts in 18 patients with leukaemia and non-Hodgkin's lymphoma. Purging was responsible for an increased incidence of graft rejection in HLA-identical transplants (13%).

Adolescent↗
PubMed1985

Idiopathic combined immunocytopenia.

Four patients with combined immunocytopenia of unknown origin were investigated. Two patients with pancytopenia had allo- and autoantibodies against erythrocytes, granulocytes and thrombocytes. Two other patients with granulocytopenia and thrombocytopenia showed allo- and autoantibodies against granulocytes and thrombocytes. All patients went into a transient or persistent remission under immunosuppressive therapy. The normalization of peripheral blood correlated with the disappearance of antibodies suggesting that the cytopenia was caused by an antibody mediated autoimmune mechanism.

Adult↗
PubMed1984

Treatment of refractory chronic idiopathic thrombocytopenic purpura with high dose intravenous immunoglobulin.

Three patients with a history of chronic idiopathic thrombocytopenic purpura stretching back over 20 years are reported. Despite splenectomy and immunosuppressive therapy satisfactory control of their disease has not been achieved. They had remained refractory to all therapeutic manoeuvres with corticosteroids and immunosuppressives for years with thrombocyte counts between 5,000 and 25,000/microliters and the concommitant risk of bleeding. This report describes the treatment of bleeding complications in these patients with high dose intravenous immunoglobulin; the peripheral blood thrombocyte count increased in all three patients from subnormal towards normal, but 2 to 4 weeks later returned to its initial low value. During the therapeutically induced raised thrombocyte count a normal bleeding time and only a moderate inhibition of thrombocyte adhesion and aggregation was observed resulting in reasonable haemostasis. High dose intravenous immunoglobulin is therefore a practical method for the control of bleeding complications in patients with refractory chronic idiopathic thrombocytopenic purpura. A clear explanation for its mode of action has not been found - the lymphocyte subpopulations remained unchanged and immunoglobulin production in vitro during the course of treatment was only minimally decreased.

Antibody Formation↗
PubMed1981

Limited value of in vitro techniques for the detection of leukocyte alloantibodies during granulocyte transfusion therapy.

A 23-year-old male patient undergoing first induction chemotherapy for acute myeloid leukaemia received granulocyte transfusions on 10 consecutive days. An average of 2.1 X 10(10) granulocytes was given per square metre body surface area per day. Transfusion reactions and absence of post-transfusion granulocyte increment after the fifth granulocyte transfusion suggested the presence of leukocyte antibodies. However, no antibodies were detectable at this time by the lymphocytotoxicity test, the indirect granulocyte immunofluorescence test, or the platelet suspension immunofluorescence test. In contrast to the clinical observation, the serological detection of leukocyte antibodies was only possible 1 day after the last granulocyte transfusion.

Adult↗
PubMed1981

In vitro and in vivo studies on filter collected granulocytes.

The in vitro function of granulocytes collected by filtration leukapheresis after premedication of donors with dexamethasone was found to be normal. In vivo studies were performed in a 21-year-old woman who was transplanted with allogeneic bone marrow for severe aplastic anaemia. The patient received granulocyte transfusions for treatment of septicaemia during the transplantation period. On 11 consecutive days an average dose of 7.2 X 10(10) granulocytes/transplantation, the patient died from cardiac failure. Transfused granulocytes were found ante mortem in a pericardial effusion and post mortem in lungs, kidneys, liver and spleen. The data indicate that filter collected granulocytes function normally in the recipient and are clinically effective.

Adult↗
PubMed1981

Granulocyte transfusions in acute leukaemia. Regeneration of granulopoiesis as determining factor of survival.

40 patients with acute leukaemia and severe granulocytopenia were treated with granulocyte transfusions for bacteriologically documented or clinically suspected septicaemia. The patients received an average of 5 transfusions each with 2.1 X 10(10) granulocytes per m2 body surface area per day. 26 patients showed clinical benefit from transfusion therapy as documented by the course of blood cultures, local lesions and fever. Only patients with regeneration of granulopoiesis had definite benefit from granulocyte transfusions. All other patients died ultimately from septicaemia.

Acute Disease↗
PubMed1980

Micromegakaryocytes in Human Bone Marrow.

Micromegakaryocytes (MMK) were defined morphologically by the cell area, nucleus form and cytoplasmic structure. Bone marrow smears of 7,156 patients were retrospectively analyzed. MMK were found most frequently and abundantly in acute non-lymphatic leukaemia, chronic myeloid leukaemia and pre-leukaemia. The presence of more than 10% MMK in the megakaryocyte population suggest a pre-leukaemic condition or non-lymphatic leukaemia. The platelet production of MMK is probably quantitatively normal although a functional defect is suspected.

Acute Disease↗
PubMedDate not supplied

Infectious complications after allogeneic bone marrow transplantation with and without T-cell depletion of donor marrow.

The infectious complications during different time intervals after allogeneic bone marrow transplantation (BMT) (day 0 to day 30, 31 to 100, 101 to 365, 366 to 730) were reviewed in 67 adult patients, 27 of whom received transplants without T-cell depletion (TCD) using methotrexate or cyclosporin A for prophylaxis of graft-versus-host disease (GvHD) and 40 of whom received donor marrow with TCD using the monoclonal anti-lymphocyte antibody campath-1 and human complement. The use of TCD reduced the incidence and severity of GvHD significantly (p less than 0.01), but was associated with an increased rate of graft rejections. During all time intervals patients with TCD had a similar, lower or statistically significantly lower number of bacterial, fungal or viral infections and a statistically significantly lower number of lethal infections (p = 0.05) as compared with patients without TCD. This finding might be explained by the fact that with TCD immunological reconstitution can take place unimpaired by GvHD or its prophylaxis or treatment, resulting in a decreased incidence of infections.

Adult↗
PubMedDate not supplied

Low cytokine contamination in buffy coat-derived platelet concentrates without filtration.

BACKGROUND: Cytokines (interleukin [IL]-1 beta, IL-6, and tumor necrosis factor [TNF]) generated by white cells during the storage of platelet concentrates can cause febrile nonhemolytic transfusion reactions. The high rate of febrile reactions reported in other studies was not observed in the patients in the authors' center. This discrepancy prompted the determination of cytokine levels in buffy coat-derived platelet concentrates. STUDY DESIGN AND METHODS: Platelet concentrates were produced from buffy coats by a standard large-scale production process. Buffy coats were separated from the red cell and plasma components, and then platelets were recovered from the buffy coats by a soft-spin procedure. Levels of cytokines (IL-1 beta, IL-6, IL-8, and TNF) were determined with commercial enzyme-linked immunosorbent assays. RESULTS: In platelet concentrates produced by the buffy coat method, IL-1 beta, IL-6, IL-8, and TNF were observed at or below the detection limit of current enzyme-linked immunosorbent assays after 5 days' storage at 22 +/- 2 degrees C. Therefore, prestorage filtration had no measurable effect on cytokine levels. In controls, IL-1 beta, IL-6, IL-8, and TNF were quantitatively detected after exogenous addition of recombinant cytokines or exposure to lipopolysaccharide. CONCLUSION: Platelet concentrates prepared from buffy coats may be virtually free of cytokines (IL-1 beta, IL-6, IL-8, and TNF) during 5 days of storage. Filtration is not required to reduce the recipient's cytokine exposure via such platelet concentrates.

Blood Platelets↗
PubMedDate not supplied

Collection of allogeneic peripheral blood progenitor cells by two protocols on an apheresis system.

BACKGROUND: Granulocyte-colony stimulating factor-mobilized allogeneic peripheral blood progenitor cells (PBPCs) are replacing bone marrow in transplantation for the treatment of several hematologic malignancies. The advantages of PBPCs are offset by the donor-associated disadvantages of granulocyte-colony stimulating factor side effects and the risk of apheresis-like platelet loss. STUDY DESIGN AND METHODS: For each individual, the first donation of allogeneic PBPCs by apheresis on the Spectra, using either the standard protocol Version 4.7 (45 donors, [Version 4.7]) or the AutoPBSC (60 donors, [AutoPBSC]) was compared. Between July 1995 and May 1996, all donors enrolled underwent Version 4.7 apheresis. Since May 1996, the majority of donors underwent AutoPBSC apheresis. For statistical analysis, only data from the first apheresis for each individual donor was considered for independent values. RESULTS: These results indicate a similar collection efficiency for CD34+ cells in the first apheresis of each donor (54% Version 4.7 vs. 53% AutoPBSC, p = 0.8). The apheresis time was longer with the AutoPBSC (233 min vs. 251 min, p = 0.005), whereas the loss of platelets was significantly lower (p < 0.001) with the AutoPBSC (28% vs. 19%). The mean number of CD34+ cells collected in the first apheresis component was 4.0 x 10(8) (Version 4.7) versus 3.8 x 10(8) (AutoPBSC). CONCLUSION: Both apheresis protocols collect sufficient numbers of PBSCs for allogeneic transplantation. The AutoPBSC operates in a fully automatic fashion, avoiding manual adjustment and interindividual variations. The loss of platelets is lower with AutoPBSC than with Version 4.7, but the apheresis time is slightly longer.

Adult↗