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M Wiesneth

Publications and source records attributed to M Wiesneth.

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

Chimerism analysis after allogeneic bone marrow transplantation with nonradioactive RFLP and PCR-AFLP using the same DNA.

We describe a method combining RFLP and PCR-AFLP analyses for studying chimerism after allogeneic bone marrow transplantation. Using RFLP analysis alone with DNA probe hMFl 87% of 244 donor/recipient pairs revealed different specific bands. By examination of the identical DNA probes using PCR-AFLP, an additional 52% of the residual donor/recipient pairs could be identified. Thus, 94% of allogeneic transplantations can be monitored using a combination of RFLP and PCR-AFLP analyses at one locus.

Bone Marrow Transplantation↗
PubMed1996

Combined CD34 positive plus CD2 negative selection for effective T-cell depletion as GvHD-prophylaxis in HLA-nonidentical blood progenitor cell transplantation.

G-CSF mobilized, T-cell-depleted peripheral blood progenitor cells (PBPC) and T-cell-depleted bone marrow (BM) were given to seven children (6 AL, 1 SCID) to prevent severe graft-versus-host-disease (GvHD) as well as graft rejection after transplantation from HLA-nonidentical parental donors. BM was T-cell-depleted by lectin agglutination and E-rosetting. For T-cell-depletion of the PBPC grafts a combination of CD34+ selection with the Ceprate SC immunoadsorption system and a subsequent depletion of CD2+ cells with immunomagnetic Dynabeads was used. The overall recovery was 0.3 (0.1-1.2)% for nucleated cells, 29 (18-45)% for CD3+ cells, respectively. The purity of CD34+ cells was 87 (68-97)% with a 0.3(0.05-0.7)% residual CD3+ T-cell contamination. In spite of the large T-cell number in the PBPC grafts the combination of CD34 positive and subsequent CD2 negative selection achieved a more than 4 log T-cell depletion and prevents severe GvHD even in HLA-nonidentical transplantation. In addition, if a high dose of progenitor cells ensures stable engraftment, this new approach could increase the possibility of wider use of HLA-mismatched family donors for transplantation.

Adult↗
PubMed1996

Improved lectin agglutination method for T-cell depletion of HLA-mismatched bone marrow grafts in children.

For T-cell depletion in HLA-nonidentical bone marrow transplantation of children with malignant diseases, we improved the original lectin/rosetting method described in 1981 by adding anti-CD2/3 coated donor red blood cells to the combination to achieve lectin agglutination in one step. Further improvements in handling led to a shortened and simplified method and better quality of the graft. Five bone marrow grafts prepared with this modified protocol contained a median number of 6 (0-28) x 10(4) T-cells per kg, corresponding to 0.02 (0-0.08)% CD3+ cells and 6 (3.7-10.5) x 10(6) CD34+ cells per kg at a median body-weight of 7 (5-38)kg. The overall recoveries after T-cell depletion were: NC 17 (10-44)%, CD34+ cells 61 (22-100)%, and CFU-GM 55 (29-212)%.

Agglutination↗
PubMed1996

Antibodies to interferon-alpha: a novel type of autoantibody occurring after allogeneic bone marrow transplantation.

Antibodies to IFN-alpha have been recognized as a novel type of autoantibody developing after allogeneic BMT. Ninety-six patients undergoing BMT for various hematologic disorders were followed for the presence of spontaneous IFN-alpha antibodies until 12 years after transplantation. Seven of them (7.3%) developed IFN-alpha antibodies occurred late after BMT (> or = 15 months), rose to very high titers in some patients, and persisted for years despite combined immunosuppressive treatment. They were oligo- or polyclonal in nature, predominantly IgG with a broad IgG subclass distribution, and neutralized the antiviral and antiproliferative activity of various natural and recombinant IFN-alpha types including the patients' endogenous IFN-alpha in vitro. All antibody-positive recipients suffered from chronic GVHD (n = 5) or chronic viral hepatitis (n = 2), but the only significant association was with prior severe aplastic anemia (3/9, 33%; P = 0.022). There was no discernible HLA association of IFN antibody development. Although the clinical relevance of the IFN-alpha antibodies is uncertain they may interfere with cellular defence mechanisms and immune regulation after BMT.

Adolescent↗
PubMed1996

Prevalence of Helicobacter pylori infection and dyspepsia in young adults in Germany.

Data on the seroprevalence and time of acquisition of Helicobacter pylori (HP) infection in Germany are scarce. We studied the seroprevalence of HP infection and the relationship with gastrointestinal (Gl) symptoms in a group of 168 German medical students in the final year of their practical training and in 260 age-matched blood donors at the University of Ulm. Eight upper Gl symptoms were scored in a questionnaire, and blood samples were taken for the detection of HP lgG antibodies with an Enzyme Immunoassay (Bio-Rad). Values greater than 12.5 U/ml (positive) were detected in 50 medical students (28.8%) and in 96 blood donors (36.9%). At least one occasional Gl symptom was present in 71.4% of medical students and 70.7% of blood donors. When related to the HP status, 27.0% of HP negative and 32.9% of HP positive individuals were completely free of symptoms. Moderate to severe dyspeptic symptoms were reported by 17.4% of HP negative and 14.4% of HP positive individuals. We conclude that the seroprevalence of HP infection in young German adults is presently about 1/3 but that HP infection is not linked to gastrointestinal symptoms in this age class.

Adult↗
PubMed1995

Autologous platelet transfusion in alloimmunized patients with acute leukemia.

Seventy-eight transfusions of autologous platelets were given to eight alloimmunized patients receiving curative chemotherapy for acute leukemia. Platelets were collected at regeneration of hematopoiesis after a chemotherapy cycle, cryopreserved with 5% dimethylsulfoxide in liquid nitrogen, and retransfused during bone marrow aplasia following the next treatment cycle. The in vitro platelet recovery after freezing, thawing, and washing was 85 +/- 4%. The in vivo corrected count increment 1 h after autologous platelet transfusions was 11 +/- 5 x 10(9)/l. With the exception of moderate urticaria and slight nausea each after one transfusion, no immediate or chronic side effects occurred. The bleeding time was shortened and hemorrhage during bone marrow aplasia was prevented in all alloimmunized patients by autologous platelet transfusions.

Acute Disease↗
PubMed1995

In vivo/ex vivo T cell depletion for GVHD prophylaxis influences onset and course of active cytomegalovirus infection and disease after BMT.

Combined in vivo/ex vivo T cell depletion is effective in the prophylaxis of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT), but influences the occurrence of active cytomegalovirus (CMV) infection and disease. Twenty nine patients receiving a T cell-depleted marrow graft (Campath-1M) after intravenous application of the monoclonal antibody Campath-1G prior to conditioning were monitored for virus shedding and antigenaemia from day -7 to day +100. In seropositive patients in this group active CMV infection occurred more frequently (10 of 16) and much earlier (nine of 10 until day +21) than in 27 seropositive patients (10 of 27, P < 0.02) receiving cyclosporin A and methotrexate (CsA/MTX). Early active CMV infection after in vivo/ex vivo T cell depletion correlated strictly with an early increase in blood lymphocyte counts (P < 0.01), with predominance of NK cells and/or CD8+ T cells. Three cases of very early interstitial pneumonitis (IP) occurred after in vivo/ex vivo T cell depletion compared with none in the CsA/MTX group. IP was fatal in the only patient with early active CMV infection, who remained lymphocytopenic till death on day +31. This may indicate that an early immune response against CMV is possible and essential for favourable clinical outcome.

Adolescent↗
PubMed1995

In vivo/ex vivo T cell depletion reduces the morbidity of allogeneic bone marrow transplantation in patients with acute leukaemias in first remission without increasing the risk of treatment failure: comparison with cyclosporin/methotrexate.

We have performed a non-randomised GVHD prophylaxis trial comparing cyclosporin/methotrexate with in vivo/ex vivo T cell depletion with the monoclonal antibodies Campath 1G/1M in patients with acute leukaemias in first complete remission. We observed significantly less acute and chronic GVHD, neutropenic fever and severe mucositis in the T cell depletion group. The incidence of graft rejection and relapses was no higher than in the cyclosporin/methotrexate group. There is a trend in favour of improved disease-free survival in the in vivo/ex vivo T cell depletion group (80% vs. 62%).

Acute Disease↗
PubMed1995

Successful therapy with donor buffy coat transfusions in patients with relapsed chronic myeloid leukemia after bone marrow transplantation is associated with high frequencies of host-reactive interleukin 2-secreting T helper cells.

Six patients treated for relapsed chronic myeloid leukaemia after allogeneic bone marrow transplantation with donor buffy coat transfusions were investigated. In the 5 patients who achieved molecular remission high frequencies of host-reactive interleukin 2-secreting T helper cell precursors (Th-p) were detectable by limiting dilution analysis. In four of the patients the presence of Th-p was associated with a clinical syndrome similar to transfusion GVHD suggesting a T cell response to minor histocompatibility antigens (minor H) expressed by both malignant haemopoiesis and host tissues. In the fifth responding patient no GVHD or bone marrow hypoplasia was observed. The nature of the antigens recognised by these donor Th-p remains unknown. No host-reactive Th-p were detectable in the non-responder and host-reactive cytotoxic T cell precursors (CTL-p) were not consistently detectable in the responding patients.

Adult↗
PubMed1994

Hepatitis C virus infection is a risk factor for liver failure from veno-occlusive disease after bone marrow transplantation.

The contribution of hepatitis C virus (HCV) infection to liver disease after bone marrow transplantation (BMT) was retrospectively evaluated in 61 patients treated with BMT. HCV genome, as well as antibodies to HCV, was analyzed in sera collected before and serially after BMT. Six patients had been infected with HCV before BMT and three patients acquired the infection during or shortly after BMT. All patients infected before BMT died within 10 weeks after transplantation. Five of these six patients (83%) died of veno-occlusive disease (VOD), compared with nine of 52 patients (17%) not infected with HCV (P < .005). Risk factors for VOD other than HCV were not more prevalent in these patients compared with uninfected patients. Parallel to the development of VOD, replication of HCV increased, as demonstrated by rising concentrations of viral RNA in serum. HCV infection acquired during or after BMT caused only mild acute hepatitis C, which progressed to chronic hepatitis C in one patient surviving 10 years after BMT. These data suggest that patients with liver disease caused by HCV infection are at high risk of developing lethal VOD after BMT.

Adolescent↗
PubMed1994

Low incidence of invasive fungal infections after bone marrow transplantation in patients receiving amphotericin B inhalations during neutropenia.

The incidence of invasive fungal infections after bone marrow transplantation (BMT) was analyzed in 303 consecutive marrow graft recipients (allogeneic n = 271, autologous n = 27, syngeneic n = 5). All patients received inhalations with amphotericin B (10 mg twice daily) during neutropenia. The overall incidence of invasive fungal infections within the first 120 days after transplant was 3.6% (11/303; aspergillosis: 6; yeast infection: 5). Four of the 11 cases occurred early, and seven cases were observed after neutrophil recovery and discontinuation of amphotericin B inhalation treatment. Late infection was significantly associated with the development of acute graft-versus-host disease. Four of the 11 infections (early 2/4; late: 2/7) were observed in patients with a history of previous fungal infection. Other patient and treatment characteristics were not helpful in defining potential risk factors. In particular, the incidence of invasive fungal infections did not differ between patients with more or less strict reverse isolation measures. Occasional side effects such as initial mild cough and bad taste were rare, usually disappeared during continued administration, and were in no case the reason for discontinuation of treatment. These data suggest that aerosolized amphotericin B may be a useful, convenient, and efficient prophylactic antifungal regimen in BMT.

Administration, Inhalation↗
PubMed1994

Cardiac toxicity of bone marrow transplantation: predictive value of cardiologic evaluation before transplant.

PURPOSE: This study analyses the risk of cardiac complications and its individual predictability in bone marrow transplantation (BMT). PATIENTS AND METHODS: One hundred seventy patients undergoing allogeneic (n = 150) or autologous (n = 20) BMT were evaluated by physical examination, history, rest and exercise ECG, chest x-ray, two-dimensional echocardiography, and radionuclide ventriculography (RNV) before BMT, and monitored for 3 months thereafter. RESULTS: Following BMT, cardiac toxicity occurred in eight patients (4.7%). Three patients (1.8%) developed life-threatening toxicity (pericardial effusion and left ventricular failure, n = 2; sudden cardiac arrest, n = 1). Thirty-eight patients (22%) had pathologic findings before BMT. In 22 patients, left ventricular ejection fraction (EF) determined by RNV was reduced to less than 55%. This was the only abnormality in 17 patients and was generally mild, with a lowest EF of 42%. There was no correlation between overall results of cardiologic evaluation before BMT and cardiac toxicity. Cardiotoxic events occurred more frequently in patients with a reduced EF (P < .05). However, this was restricted to minor cardiac events. Life-threatening cardiac toxicity was not significantly increased in patients with pathologic results before BMT. Moreover, none of the patients with an EF less than 50% developed cardiac toxicity. CONCLUSION: Life-threatening cardiac toxicity is rare after BMT, occurring in less than 2% of all patients. Although the occurrence of cardiac toxicity is correlated with a reduction of EF before BMT, life-threatening cardiac toxicity cannot be predicted in individual patients.

Adolescent↗
PubMed1994

High-titre interferon-alpha antibodies in a patient with chronic graft-versus-host disease after allogeneic bone marrow transplantation.

In a patient undergoing allogeneic BMT for chronic phase CML, de novo chronic GVHD developed within 80 days after transplantation. Eighteen months post-BMT, high serum levels of neutralizing interferon-alpha (IFN-alpha) antibodies were detected, which persisted despite continuous immunosuppressive treatment. The antibodies were of oligoclonal or polyclonal origin, predominantly of the IgG1 type, and reacted broadly with various human IFN-alpha types, including the patients endogenous IFN-alpha, but failed to recognize natural IFN-beta and recombinant IFN-gamma. Pathogenesis and clinical impact of the IFN-alpha antibodies are unknown. Antibodies of cytokines are a novel class of autoantibodies that may develop after allogeneic BMT and interfere with cytokine homeostasis and immune regulation.

Adult↗
PubMed1994

[Leukocyte transfusion as therapy of recurrent CML after allogenic bone marrow transplantation].

Eight patients with relapsed chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation (BMT) were treated with alpha-interferon and leukocyte transfusions of the bone marrow donor. Six patients responded with disappearance of leukemic cells (Ph1, BCR-ABL) and reestablished donor hemopoiesis. All six patients developed bone marrow hypoplasia and graft-versus-host disease (GvHD). Three of the six patients died of cerebral bleeding, infection and GvHD, respectively. The remaining three patients are alive and well at day 418, 677, 818 after leukocyte transfusions. Two patients relapsed with more advanced disease of CML after BMT and failed treatment. Donor leukocyte transfusions provide an effective therapy for patients with relapsed CML after BMT, but are associated with a high mortality due to bone marrow hypoplasia and GvHD.

Antigens, CD↗
PubMed1993

Analysis of antibody response to the measles virus using synthetic peptides of the fusion protein. Evidence of non-random pairing of T and B cell epitopes.

The measles virus induces a life-long immune response associated with antibodies specific for the fusion protein. To map the linear immunodominant recognition sites of the fusion (F) protein of the measles virus, we have reacted a complete set of 108 overlapping pentadecapeptides with purified IgG obtained from donor sera with elevated anti-measles titers. The antibodies recognized about 20% of the peptides and generated a characteristic binding pattern, defining about 6 or 7 distinctive regions (31-75; 111-145; 151-165; 191-215; 271-320; 421-440; 481-530) which include the major hydrophobic segment (111-145) of the intersubunit region and the C-terminal Cys-cluster region. The binding sites were located in close proximity of the few experimentally defined T cell epitopes. This pairing of T and B cell epitopes was corroborated by computer-assisted T cell prediction. The significance of a non-random association of T and B cell epitopes for processing and presentation is discussed. It is speculated that in long-term immunity against measles (F protein), B cells of the same sIg specificity play an important role both as antigen presenting cells and as antibody producing cells. In contrast to human sera from late convalescent donors, mouse and rabbit MV antisera with high neutralizing titers as well as neutralizing MV-F specific monoclonal antibodies did not react with the peptides.

Adult↗