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Biomedical subjects

W Hinterberger

Publications and source records attributed to W Hinterberger.

At least 73 records · Page 4Linked to original sources
PubMed1991

[Chronic myeloid leukemia].

Chronic myelocytic leukemia is a malignant clonal disorder which, after a chronic phase of about 3 to 4 years, progresses to blastic transformation. The disease is incurable by conventional cytostatic treatment. Once blastic transformation has ensued, survival is limited to weeks or months. Interferon may prolong the chronic phase, but data are controversial. Allogeneic bone marrow transplantation may cure 40 to 70% of patients treated while in chronic phase. Survival is about 20% in advanced disease, depending mainly on age, sex of donor and clinical condition. Allogenic bone marrow transplantation was hitherto restricted to patients having an HLA-identical bone marrow donor. Volunteer bone marrow donor registries now contain about 400,000 registered unrelated healthy donors: The chance of finding an unrelated bone marrow donor is now between 10 and 60%, and the chance will increase when donor registries expand.

Antineoplastic Agents↗
PubMed1991

[Chronic lymphatic leukemia].

Chronic lymphocytic leukemia is a B-lymphocyte derived clonal malignant disorder. Presently available chemotherapy is only palliative and is withheld unless typical symptoms evolve. Newly developed cytostatic drugs such as Fludarabine, Pentostatin and 2-Chlorodeoxyadenosin have shown promising activity in cases otherwise resistant to conventional chemotherapy. Allogeneic bone marrow transplantation has been successfully applied in some younger patients. Bone marrow transplantation at this time represents the only curative therapeutic modality and should be considered in younger patients having a suitable donor.

Antineoplastic Agents↗
PubMed1991

[Severe aplastic anemia].

Severe aplastic anemia is a rare disorder which is most often fatal when bone marrow transplantation or an immunosuppressive regimen is not applied. The cause of the disease in individual patients is not identifiable by laboratory investigations. The decision for a therapeutic modality is based on patient age and availability of an HLA-identical bone marrow donor. Early application of bone marrow transplantation may cure up to 80% of patients. Many patients may also be rescued with combined, intensive immunosuppression. Each of these treatment modalities, however, require early application, prior to the onset of typical complications such as infection and bleeding.

Anemia, Aplastic↗
PubMed1991

[Allogenic bone marrow transplantation in acute leukemia].

Allogeneic bone marrow transplantation (BMT) allows application of supraletal chemoradiotherapy thereby sparing of hemopoietic tissue. After ablation of hematopoiesis bone marrow of a healthy and HLA-identical donor has to be transplanted. During aplasia patients require maintenance in sterile units (reverse isolation or lamina air flow). These together with intestinal decontamination is aimed to reduce the occurrence of infections in these severely immunocompromised patients. To minimize BMT-specific complications such as marrow graft rejection, Graft versus host disease (GVHD) or infections with cytomegalovirus or pneumocystis carinii various prophylactic measures are given. In younger patients with acute myeloid leukemia (AML) in first complete remission cure can be achieved in up to 70% by allogeneic BMT. If BMT is performed beyond first remission cure can be expected in about 20%. In acute lymphoblastic leukemia (ALL) the situation is more complex; besides blood cell count at diagnosis variables such as cytogenetics, immunophenotype, response to induction therapy and patient's age have to be taken into account for ultimate therapeutic decisions.

Bone Marrow Transplantation↗
PubMed1990

Recombinant human interleukin-3 expands the pool of circulating hematopoietic progenitor cells in primates--synergism with recombinant human granulocyte/macrophage colony-stimulating factor.

The in vivo effect of recombinant human interleukin-3 (rhIL-3) on peripheral blood (PB) levels of hematopoietic progenitor cells was studied in nonhuman primates. Subcutaneous administration of 33 micrograms/kg/d of rhIL-3 for 11 to 14 days to rhesus monkeys slightly raised leukocyte counts (twofold) and substantially expanded the pool of circulating stem cells in the second week of treatment. At the end of rhIL-3 administration, PB levels of granulocyte/macrophage colony-forming units (CFU-GM) increased by a mean of 12-fold; burst-forming units-erythroid (BFU-E) by ninefold; CFU-mix, by 12-fold; and CFU-megakaryocyte (Mk), by 13-fold as compared with their respective pretreatment values. Subsequent administration of recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF; 5.5 micrograms/kg/d for 5 days) to rhIL-3-pretreated animals further expanded the PB stem cell compartment leading to maximum levels of CFU-GM that were in average much more increased (63-fold) than CFU-GM levels under rhIL-3 (14-fold) or rhGM-CSF (12-fold) alone. This hitherto unknown effect of rhIL-3 on the pool of circulating progenitors, particularly in synergy with rhGM-CSF, may facilitate harvest of hematopoietic progenitor cells from PB for stem cell transplantation.

Animals↗
PubMed1990

Photochemotherapy improves chronic cutaneous graft-versus-host disease.

We have used oral psoralen photochemotherapy (PUVA) to treat four patients with chronic graft-versus-host disease of the skin, oral mucosa, and liver, who had responded only partially to long-term immunosuppressive therapy (prednisolone, cyclosporine, azathioprine). PUVA therapy was delivered to the entire skin but not to the oral mucosa, and immunosuppressive therapy was continued in all patients. Two patients' skin lesions improved considerably; the oral lesions healed and did not recur in one. Immunosuppressive therapy could be reduced in these two patients. One patient with sicca signs did not improve. One patient had to interrupt PUVA therapy because of side effects attributed to 8-methoxypsoralen (nausea and vomiting). No flare of acute cutaneous graft-versus-host disease was noted during PUVA therapy. Chronic graft-versus-host disease of the liver did not improve in any patient.

Adolescent↗
PubMed1990

Recombinant human erythropoietin activates a broad spectrum of progenitor cells.

Twenty uremic patients on regular hemodialysis received recombinant human Erythropoietin (rhEPO) in a dosage of 50 U/kg body wt (N = 9) and 80 U/kg body wt (N = 11), respectively, three times weekly. The number of circulating hemopoietic progenitor cells colony-forming unit-granulocyte-erythrocyte-macrophage (CFU-mix), burst-forming unit-erythroid (BFU-E) and colony-forming-granulocyte-macrophage (CFU-GM) in peripheral blood were assayed weekly by means of a commonly applied in vitro clonal assay. A significant increase of peripheral CFU-mix, BFU-E and CFU-GM could be observed within one week of supplementation therapy in both groups. The increase of BFU-E was followed by a rise of hematocrit within four and three weeks, respectively. These results suggest that the stimulatory in vivo effect of rhEPO administered in therapeutical doses is not restricted to the erythroid lineage but also includes progenitor cells committed to the myeloid lineage (CFU-GM) as well as the multipotent progenitors CFU-mix. The increment of circulating progenitor cells was seen with a dosage of 80 U/kg body wt and 50 U/kg body wt as well.

Anemia↗
PubMed1990

1-Deamino-8-D-arginine vasopressin in the treatment of non-haemophilic patients with acquired factor VIII inhibitor.

1-Deamino-8-D-arginine vasopressin (DDAVP) was administered to 3 patients with spontaneous factor VIII inhibitors. In 2 patients with baseline factor VIII levels above 1%, a marked increase of factor VIII activity after DDAVP infusion could be observed. No rise of factor VIII activity after DDAVP was seen in the 3rd patient with a baseline factor VIII level of less than 1%. Daily infusion of DDAVP resulted in a reduction of the efficacy, but the full effect could be retained when DDAVP was given at 48-hour intervals. The effect of DDAVP infusion on factor VIII levels in the 2 responding patients was superior to the treatment with 30 U/kg factor VIII concentrate and approximately equivalent to infusion of 45 U/kg factor VIII concentrate. DDAVP may be a useful and less expensive treatment for patients with acquired factor VIII inhibitors and a baseline factor VIII level of more than 1%.

Aged↗
PubMed1990

Gamma-interferon in myelodysplastic syndromes: a pilot study.

Eight patients with myelodysplastic syndrome (MDS; RA = 1, RAEB = 2, RAEB-t = 4, CMML = 1) received three cycles of recombinant gamma-IFN administered in 2-week intervals, each consisting of a 14-day period of subcutaneous injections at a daily dose of 0.1 mg/m2. Neither a complete nor a partial remission could be obtained. There was only one definite improvement consisting in a rise of hemoglobin level from 7 to more than 12 g/dl. Two minor improvements were due to a slight rise of platelet counts. Three patients developed acute leukemia under treatment with gamma-IFN. Our data suggest that gamma-IFN administered according to the treatment schedule as used in our trial has only a minimal beneficial effect in patients with MDS.

Adult↗
PubMed1990

Autologous rescue with blood-derived stem cells in a child with non-Hodgkin's lymphoma.

Autologous blood-derived stem cells were used for stem-cell rescue in a 5-year-old boy with chemotherapy-resistant B-Non-Hodgkin's lymphoma (B-NHL) involving bone marrow. The high dose chemoradiotherapy was carried out 5 months after initial diagnosis during partial remission. The preparative regimen consisted of 12 Gy fractionated, total-body irradiation (FTBI) before 60 mg/kg etoposide. There were 22.96 X 10(4)/kg body weight myeloid precursor cells, granulocyte-macrophage committed stem cells (CFU-GM) collected by intermittent blood flow separation with a Haemonetics 30R in two cytaphereses and stored in liquid nitrogen. Also 11, 82 X 10(4) CFU-GM/kg body weight were recovered and transfused after thawing. Rapid hematopoietic reconstitution ensued: Erythroid precursors were detected on day 9, 1 X 10(9)/L leucocytes were counted on day 11, and 0.5 X 10(9)/L granulocytes on day 13, respectively. The patient required 3 single-donor platelet transfusions, the last one on day 10. On day 17, 100 X 10(9)/L platelets were reached. A bone marrow aspirate on the same day showed good trilineage regeneration. The patient remained in complete remission 7 months after autografting with a normal stem cell content of the bone marrow and in the peripheral blood. On day 226, after stem cell infusion, a bone marrow relapse occurred.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Interleukin-3 is a differentiation factor for human basophils.

The effect of recombinant human (rh) cytokines, interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), monocyte/macrophage colony stimulating factor (M-CSF), interferon-alpha (IF-alpha), interferon-gamma (IF-gamma), and the tumor necrosis factor-alpha (TNF-alpha) on differentiation and function of metachromatic cells (MCS) was studied. Among all cytokines tested, rh interleukin-3 (rhIL-3) selectively induced a significant formation of MCS (IL-3: 1.1 +/- 0.6 x 10(5) v control: 0.02 +/- 0.15 x 10(5) MCS/mL suspension) and dose dependent increase in formation of intracellular histamine (IL-3, 100 U/mL: 95 +/- 23 ng/mL v control: 1.8 +/- 0.8 ng/mL) in a bone marrow suspension culture system (analyzed on day 14 of culture). Besides MCS, formation of eosinophils was observed in this culture system in the continuous presence of rhIL-3, whereas IL-3 pulse-stimulation for three hours and subsequent exposure to control medium induced growth of MCS but not of eosinophils. By combined immunofluorescence/toluidine blue staining, MCS were found to express a cell surface marker profile that corresponds to the immunological phenotype of peripheral blood basophils (MY-7(CD13)+, VIM12(CD11b)+, VIM2+, MAX1-, MAX24- and YB5B8-). Furthermore, cultured MCS expressed surface membrane receptors for IgE and could be triggered for nontoxic histamine release by a monoclonal anti-IgE antibody. To evaluate a possible influence of IL-3 on basophil function, studies were extended to freshly obtained blood basophils (healthy volunteers, n = 3). However, like all other cytokines tested, rhIL-3 failed to induce basophil histamine release. Taken together, our studies demonstrate that IL-3 is a differentiation factor for human basophils.

Antibodies, Monoclonal↗
PubMed1989

Mast cell typing: demonstration of a distinct hematopoietic cell type and evidence for immunophenotypic relationship to mononuclear phagocytes.

The immunologic surface marker profile of human mast cells (MCs) was established using a combined toluidine/immunofluorescence staining procedure [49 monoclonal antibodies (MoAbs) tested]. Ascites (n = 9) MCs as well as enzymatically dispersed MCs from all organs tested (lung n = 11, skin n = 7, intestinum n = 10) exhibited an identical marker profile. MCs were recognized by MoAbs clustered as CD9 (anti-gp24), CD33 (anti-gp67), and CD45 (anti-gp220) as well as by MoAbs directed against membrane-bound IgE. MoAB YB5B8 (anti-gp145) selectively recognized MCs. Most significantly, however, MCs were stained by MoAbs MAX1 (anti-gp65), MAX3 (anti-gp68), MAX11 (anti-gp65), and MAX24 (anti-gp65). These antibodies bind to surface membrane antigens associated with a late stage of monocyte/macrophage differentiation. Thus, our results provide definite evidence that MCs share surface membrane markers with mononuclear phagocytes. In contrast, MCs are stained neither by lymphatic markers (CD1-8, 10, 19-24) nor by myelomonocytic markers (CD11-17). MCs also lack the interleukin-2 (IL-2) receptor (CD25), the T10 antigen (CD38), and most of the myelocytic markers expressed on peripheral blood (PB) basophils. Thus, MCs displayed a unique phenotype within the hematopoietic system. This new approach enabled us to enrich human lung MCs to a purity greater than 95% by means of negative selection with complement-mediated cell lysis. Purified MCs were subsequently stained with MoAbs and analyzed by flow cytometry, which confirmed the results obtained from the double-staining experiments. We next examined cultured metachromatic cells derived from bone marrow (BM) and peripheral blood colony-forming units (CFU). These metachromatic cells previously could not be classified by morphologic criteria alone and have therefore been termed basophil-like/MC-like cells. In this study, toluidine blue-positive cells obtained from either pooled multipotential colonies (day 14-CFU-GEM) or pooled myelocytic colonies (day 16/17-CFU-GM/G/M) were recognized by MoAbs MY7 (CD13), VIM12 (CD11b), and VIM2, as well as by an anti-IgE MoAb, after preincubation with IgE. In contrast, CFU-derived metachromatic cells were not stained by MoAb YB5B8. This marker profile corresponds to the immunologic phenotype of blood basophils and excluded a detectable formation of mature MCs in colonies derived from cultured hematopoietic stem cells.

Antigens, Surface↗
PubMed1989

Identification of activated T cells and the suppressor/inducer subset in patients suffering from severe aplastic anemia.

In patients with severe aplastic anemia (SAA), lymphocyte subpopulations were examined for the presence of HLA-DR and 2H4 (suppressor/inducer subset) antigen-expressing cells by flow cytometric analysis. Investigations were performed on peripheral blood lymphocytes before and after therapy with antithymocyte globulin (ATG) and methylprednisolone (MP), as well as on bone-marrow lymphocytes before therapy. Before treatment, only the absolute numbers of CD4+ T cells and the CD4+HLA-DR+/CD8+HLA-DR+ activated T cell ratio were significantly decreased (p less than 0.01 and p less than 0.001, respectively). Following successful ATG/MP treatment, a decrease in the CD4+/CD8+ T cell ratio was found. Regarding the suppressor/inducer subset, only absolute numbers of CD4+/2H4+ cells were somewhat higher in treated patients; the percentages were the same in all groups of patients. Studies performed on bone-marrow lymphocytes showed significantly decreased percentages of CD4+ and CD8+ T lymphocytes, which also express HLA-DR antigen. No significant changes in the distribution of activated T cells following ATG/MP therapy were found, suggesting that these cells play no major role in the pathogenesis of the disease.

Anemia, Aplastic↗
PubMed1989

Identification of the target platelet glycoprotein in autoimmune thrombocytopenia occurring after allogeneic bone marrow transplantation.

We report the case of a patient who developed autoimmune thrombocytopenia after allogeneic bone marrow transplantation from her HLA-identical sister. An IgG autoantibody was detected that bound to the platelet glycoprotein IIb/IIIa and to the HLA class I proteins. Immunoprecipitation studies with radiolabeled platelets revealed additional antibody binding sites on proteins of 214 kDa molecular weight under nonreduced conditions and 65 and 56 kDa molecular weight under reduced conditions.

Adult↗
PubMed1989

Immune thrombocytopenia more than a year after allogeneic marrow transplantation due to antibodies against donor platelets with anti-PlA1 specificity: evidence for a host-derived immune reaction.

We report on a male patient transplanted from his HLA-matched sister for Ph1-chromosome positive chronic myelogenous leukaemia who developed immune thrombocytopenia more than 1 year after transplantation. The platelet antibody reacted with the platelet specific antigen PlA1 on donor platelets, and also on recipient platelets after engraftment. A presumed host-versus-donor induced thrombocytopenia was supported by Southern blot analysis using a Y-chromosome specific probe demonstrating residual host-origin cells in the patient's excised spleen.

Adult↗