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D Bunjes

Publications and source records attributed to D Bunjes.

80 records · Page 5Linked to original sources

Treatment results of nine patients with Burkitt's lymphoma.

From 6/79 until 2/86, 9 patients (median age 39) with Burkitt's lymphoma were treated. Stage D disease was seen in 7 cases, stage C in two and stage A in one. The main symptom was abdominal pain or a rapidly progressing abdominal tumor. Three patients had bone marrow involvement and two had a Burkitt's leukemia. Three had typical chromosomal aberrations. Therapy consisted of a variety of chemotherapy regimens plus additional radiotherapy and/or bulk surgery. Two patients achieved complete remissions (of 6 and 20+ months duration), and 4 partial remissions were obtained. The remaining patients had either progressive, drug resistant disease or died early. One patient is currently alive and in complete remission at 20+ months. A second patient is alive at 20+ months in partial remission with traces of IgM-paraprotein still detectable. The main causes of death were tumor-lysis syndrome (4 patients) and therapy related sepsis with progressive tumor (3 patients). This poor outcome is probably due to a high proportion of high-risk patients and suboptimal therapy for this rapidly proliferating tumor.

Adolescent↗

Cyclosporine as an alternative to cyclophosphamide in the treatment of chronic graft-versus-host disease.

Four patients with progressive extensive chronic graft-versus-host disease or dose-limiting toxicity on conventional therapy (cyclophosphamide + prednisolone) were treated with a regimen of cyclosporine + prednisolone as induction therapy and cyclosporine as maintenance therapy. All 4 showed clinical improvement and 3 of 4 are alive at 9 months. The incidence of infections was not affected by this regimen, but steroid requirements were reduced.

Acute Disease↗

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↗

Frequency analysis of cyclosporine-sensitive cytotoxic T lymphocyte precursors.

The influence of the immunosuppressant cyclosporine (CsA) on the antigen-driven activation of resting cytotoxic T lymphocyte precursors (CTL-p) and on the reactivation of mixed-lymphocyte-reaction-primed CTL, is analyzed at the clonal level. Using the limiting-dilution culture approach, we show that the majority (60-90%) of clones of CTL-p with specificity for given antigens are not activated in the presence of CsA; a minority (10-40%) of CTL-p are CsA-resistant. This is so for alloantigen-reactive CTL-p and major-histocompatibility-complex-restricted CTL-p with hapten specificity. In contrast, the frequency of CTL grown out of primed mixed lymphocyte culture cells is not influenced by CsA. Although CsA does not interfere with the short-term growth of I1-2-driven activated T cells, it may influence the expression of their cytolytic potential.

Animals↗

Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 1 and interleukin 2.

The site of action of the immunosuppressive drug cyclosporin A in in vitro cytotoxic allograft responses has been localized. General cytotoxic effects of the drug on proliferating T cells became apparent at concentrations of 500-1000 ng/ml, while selective effects were observed at concentrations of 10-100 ng/ml. The selective effects included a blockade of interleukin 2 release from activated T helper cells on the one hand and inhibition of interleukin 1 release from splenic adherent cells on the other. While cyclosporin A did not interfere with the intracellular events required for the activation and subsequent clonal expansion of alloreactive T cells, the lack of interleukin 1 and interleukin 2 induced by cyclosporin A results in an inability of T responder cells to mount cytotoxic allograft responses in vitro.

Animals↗

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↗

Outcome of peripheral blood stem cell mobilization in advanced phases of CML is dependent on the type of chemotherapy applied.

High-dose chemotherapy with autologous transplantation of in vivo purged PBSC is a novel investigational approach to treating chronic myelogenous leukemia (CML) patients not responsive to conventional therapy with interferon-alpha (IFN-alpha) and not eligible for allogeneic transplantation. PBSC mobilization using either '5+2/7+3'-type chemotherapy or 'mini-ICE/ ICE' chemotherapy was investigated in 43 patients with advanced phases of Philadelphia (Ph)-positive CML. Thirty patients were in late chronic phase (>12 months post diagnosis) and 13 patients in accelerated phase (AP) or blast crisis (BC). Contamination with Ph-positive cells was evaluated in harvests from 37/43 patients. The outcome of PBSC mobilization was dependent on the type of chemotherapy administered: a complete or major cytogenetic response (<35% Ph-positive metaphases) in leukapheresis collections was obtained in ten of 15 patients treated with 'mini-ICE/ICE' but in only three of 28 patients treated with '5 + 2/7 + 3' chemotherapy. One patient (1/43) in blast crisis died during mobilization therapy (2%). Twenty-five patients underwent PBSC transplantation and all of them engrafted successfully. Transplantation-related mortality was 0%. The data show that in advanced phases of CML the chance of harvesting Ph-negative peripheral blood stem cells depends on the type of chemotherapy used for mobilization.

Adult↗