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K Geissler

Publications and source records attributed to K Geissler.

At least 37 records · Page 2Linked to original sources
PubMed2001

IL-10 increases the number of CFU-GM generated by ex vivo expansion of unmanipulated human MNCs and selected CD34+ cells.

BACKGROUND: Ex vivo expansion strategies with different cytokine combinations are currently used by several groups as a means of increasing the number of HPCs for a variety of special clinical applications. Because there is little information on the potential role of IL-10 in such ex vivo expansion models, the effect of this cytokine on the generation of myeloid progenitor cells in suspension cultures was investigated. STUDY DESIGN AND METHODS: On the basis of data from the literature and from new experiments, the combination of SCF and IL-3 at concentrations of 100 ng per mL and 100 U per mL, respectively, was chosen as the standard cocktail. The addition of IL-10 to such cultures resulted in a marked and dose-dependent potentiation of myeloid progenitor cell production. RESULTS: Using unmanipulated leukapheresis components from 13 individuals (including lymphoma and cancer patients and normal donors), the expansion multiple of CFU-GM after 14 days as compared with pre-expansion values was 9.54 +/- 2.31 times by SCF/IL-3 and 46.38 +/- 7.37 times by the combination of SCF/IL-3 and 100 ng per mL of IL-10 (p<0.001). IL-10 also potentiated CFU-GM generation from selected CD34 PBMNCs (n = 9) with an expansion of 17.22 +/- 7.04 times versus 45.67 +/- 16.78 times using the SCF/IL-3 and SCF/IL-3/IL-10 combination, respectively (p<0.05). Moreover, expansion-promoting effects of IL-10 were observed in liquid cultures containing MNCs from bone marrow (n = 4) and cord blood (n = 3), but did not reach statistical significance because of the small number of samples. CONCLUSION: These results suggest IL-10 as a useful cytokine to optimize progenitor cell-expansion strategies for clinical application.

Antigens, CD34↗
PubMed2001

Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication: clinical and laboratory effects.

A variety of health effects have been attributed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but little information is available on the course of a verified high-level TCDD intoxication. In this paper we describe two cases of heavy intoxication with TCDD and present a 2-year follow-up including clinical, biochemical, hematologic, endocrine, and immunologic parameters monitored in two women, 30 and 27 years of age, who suffered from chloracne due to TCDD intoxication of unknown origin. Patient 1, who had the highest TCDD level ever recorded in an individual (144,000 pg/g blood fat), developed severe generalized chloracne, whereas in the second patient, despite heavy intoxication (26,000 pg/g blood fat), only mild facial acne lesions occurred. Both patients initially experienced nonspecific gastrointestinal symptoms. In Patient 1 we observed a moderate elevation of blood lipids, leukocytosis, anemia, and secondary amenorrhoea. The laboratory parameters in Patient 2 were all normal. Despite the high TCDD levels, apart from chloracne, only few clinical and biochemical health effects were observed within the first 2 years after TCDD intoxication.

Acneiform Eruptions↗
PubMed2000

[Therapeutic potential of thrombopoietin].

Thrombocytopenia induced by disease and/or chemotherapy is one of the major complications in the treatment of patients with hemato-oncological malignancies. The discovery of Mpl ligand, a hematopoietic growth factor that stimulates megakaryopoiesis and thrombopoiesis lineage-specifically both in vitro and in preclinical models, is an important step in the development of new treatment concepts for patients with thrombocytopenia. Two recombinant forms of Mpl ligand, recombinant human thrombopoietin (rHuTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), are currently being tested in clinical trials. Development of these thrombopoietins has recently been constrained due to the observation of anti-thrombopoietin antibodies in some patients following thrombopoietin treatment. However, clinical trials performed so far provide significant insight into the therapeutic potential of these molecules. TPO/MGDF stimulates thrombopoiesis in cancer patients before chemotherapy and reduces the duration and sometimes the degree of thrombocytopenia following myelosuppressive chemotherapy. Despite marked thrombocytosis in some of these patients an increased risk for thromboembolic complications was not observed. Although administration of TPO/MGDF has provided some clinical benefit after autologous bone marrow transplantation, such effects have not been found in the settings of peripheral blood stem cell transplantation and aplasiogenic AML chemotherapy. The potential role of Mpl ligand in other indications such as thrombocytopenia in liver disease, plateletpheresis and stem cell expansion remains to be determined. Recent efforts in the development of thrombopoietins focus on the generation of molecules with maintained thrombopoietic activity which are not immunogenic.

Blood Platelets↗
PubMed2000

Efficacy of standard treatment in patients with Hodgkin's disease--a single center experience.

Sixty-two consecutive patients with newly diagnosed Hodgkin's Disease (HD) were treated at our institution between 1991 and 1998 in accordance with protocols which we considered as optimal standard therapy. In patients with localised disease, extended field irradiation alone was used initially but short duration chemotherapy followed by involved field irradiation was given later. Initially, MOPP/ABV chemotherapy was considered the standard treatment regimen for advanced HD, subsequently it was replaced by ABVD treatment. At 5 years patients with localised HD have a projected overall survival of 95% and a failure-free survival of 72%. Relapses in patients treated with radiotherapy alone (6/16 cases) could be successfully managed with chemotherapy in most cases (5/6). In advanced HD, projected 5-year survival and failure-free survival are 100% and 80%, respectively. No treatment-related deaths or secondary malignancies were registered.

Adolescent↗
PubMed2000

Effects of erythropoietin on platelet reactivity and thrombopoiesis in humans.

A recent study in dogs suggested that erythropoietin (EPO) not only promotes the synthesis of increased numbers of reticulated platelets but that these newly produced platelets are hyperreactive compared with controls. Because of the increasing use of EPO in the perioperative setting, we characterized the effects of EPO on platelet reactivity in healthy human volunteers. In a randomized, controlled trial, we studied the effects of EPO on platelet reactivity, thrombopoiesis, and endothelial activation in circumstances similar to those of autologous blood donation. Thirty healthy male volunteers received placebo or EPO (100 or 500 U/kg of body weight given intravenously) three times a week for 2 weeks and underwent phlebotomy on days 8 and 15. Thrombin receptor-activating peptide induced expression of P-selectin, and CD63 increased 2- to 3-fold during EPO treatment. The enhanced platelet reactivity was also reflected by a 50% increase in soluble P-selectin in plasma. Plasma E-selectin levels increased in a dose-dependent fashion by more than 100% during EPO treatment, indicating substantial activation of endothelial cells. A 10% to 20% increase in platelet counts was observed in both EPO groups on day 5. In the placebo group, platelets increased only several days after the first phlebotomy. The increase in platelet counts was not reflected by changes in the amounts of reticulated platelets or circulating progenitor cells. In summary, we found that EPO markedly enhances endothelial activation and platelet reactivity, which may adversely affect patients at cardiovascular risk. However, the increased platelet reactivity could be exploited in patients with platelet dysfunction. (Blood. 2000;95:2983-2989)

Adult↗
PubMed2000

Role of immunological lymphocyte subset typing as a screening method for lymphoid malignancies in daily routine practice.

BACKGROUND: The major diagnostic role of peripheral lymphocyte subset typing is to distinguish between malignant and reactive conditions. METHODS: The present study evaluates the screening efficacy of flow cytometric lymphocyte subset typing for the presence of a lymphoid malignancy. Four hundred samples were analyzed with a combination of anti-T-, B-, and natural killer (NK)-cell monoclonal antibodies. RESULTS: Two hundred and twenty (55%) samples showed a normal distribution of lymphocyte subsets, 73 (18%) samples exhibited unspecific alterations of lymphocyte subsets, 19 (5%) samples exhibited a reactive phenotype typical of Epstein-Barr virus/cytomegalovirus (EBV/CMV) infection, and 88 (22%) samples expressed a phenotype suggestive of lymphoma. The most predictive independent factor of a lymphoma-specific phenotype was the absolute lymphocyte count (P = 0.0001, odds ratio 73.225). Seventy-eight percent of samples containing >/=4 x 10(9)/l lymphocytes and 2% of samples with lymphocyte counts <4 x 10(9)/l exhibited a lymphoma-specific phenotype. The specificity of the referring clinical comment was the second best predictor of a lymphoma-specific typing outcome (P = 0.0001, odds ratio 19.589). The independent predictive values of lymphocyte morphology and of relative lymphocyte counts were of borderline significance. CONCLUSIONS: The use of flow cytometric lymphocyte subset typing as a diagnostic screening method for lymphoma should be restricted to cases of unexplained elevation of absolute lymphocyte counts with or without morphological atypias and to cases with definite clinical symptoms of lymphoma.

Cytomegalovirus Infections↗
PubMed2000

Macrocytic anemia and thrombocytosis associated with thymoma: a case report.

Thymomas are often associated with autoimmune disorders. We report on a 45-year-old female patient with thymoma and hypogammaglobulinemia (Good's syndrome) who developed symptomatic macrocytic anemia (Hb 4.4 g/dl, MCV 112 fl) and thrombocytosis (Plt 442 G/l). Besides hypogammaglobulinemia (IgG 589 mg/dl), an inverted ratio of CD4(+)/CD8(+) cells was seen. The bone marrow biopsy showed a slightly hypercellular bone marrow with normal granulopoiesis, normal megakaryopoiesis and a mild dyserythropoiesis without any ring-sideroblasts. The in-vitro stem cell culture from the bone marrow revealed an atypical growth of macroclusters, reduced BFU-E and CFU-GEMM colony growth, whereas the CFU-GM colony growth was within the normal range. The chromosomal analysis showed a normal karyotype. The plasma vitamin B(12) and folate levels were within normal ranges, and we could not detect any autoantibodies. These findings excluded the differential diagnoses pure red cell aplasia (PRCA) and pernicious anemia. After resection of the thymoma of mixed cell type, the macrocytic anemia and thrombocytosis disappeared. The clinical course was complicated by a cerebral palsy and a life-threatening fungal septicemia after surgery. In the third year after thymectomy, hyporegenerative macrocytic anemia and thrombocytosis reappeared and an immunosuppressive treatment with prednisolone (1 mg/kg BW) was started. After initiation of the prednisolone therapy, reticulocyte counts increased and macrocytic anemia as well as thrombocytosis disappeared. The normalization of these laboratory parameters during glucocorticoid therapy suggests that in rare cases the constellation of macrocytic anemia, thrombocytosis and hypogammaglobulinemia may be due to an underlying immunologic mechanism.

Agammaglobulinemia↗
PubMed2000

Culture requirements for induction of dendritic cell differentiation in acute myeloid leukemia.

Peripheral blood mononuclear cells (PBMCs) from 15 newly diagnosed acute myeloid leukemia (AML) patients were cultured in fetal calf serum-free media supplemented with either granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-4 and tumor necrosis factor alpha (TNFalpha), or GM-CSF, stem cell factor (SCF), TNFalpha and transforming growth factor beta (TGFbeta) in order to generate leukemia-derived dendritic cells (DCs). Cultured cells were analyzed by flow cytometry with respect to DC-associated surface molecules (CD1a, CD83, CD40, CD80, CD86, HLA-DR) when they showed significant DC morphology in culture (14 cases). After cultivation, neo-expression or upregulation of CD1a antigen was found in 8 samples, CD83 in 2, CD40 in 14, CD80 in 7, and CD86 in 9. Twelve of 14 AMLs, in which DC morphology could be induced upon cultivation, showed upregulation of at least 2 DC-associated molecules. For induction of DC differentiation. GM-CSF, IL-4 plus TNFalpha was superior in 11 cases, and better results were obtained with GM-CSF, SCF, TNFalpha plus TGFbeta in 3 cases. In 7 of 14 samples tested, a marked increase of the T-cell stimulatory capacity could be demonstrated in the allogeneic mixed lymphocyte reaction. The leukemic origin of in vitro-generated DCs was demonstrated by fluorescence in situ hybridization in a patient with translocation t(15;17). Our results suggest that the use of different culture conditions may extend the number of AML patients in which a differentiation towards the DC lineage can be induced in vitro.

Acute Disease↗
PubMed2000

Fludarabine therapy in Waldenström's macroglobulinemia.

Seven patients with macroglobulinemia (six previously untreated, one with minimal pretreatment) were treated with fludarabine (25 mg/m2/day for 5 days, repeated every 4 weeks). The median age was 58 years. The time from diagnosis to treatment with fludarabine was 4.5 months to 175 months (median 32.6 months). The patients received six (n =5), five (n =1), and three (n = 1) courses of fludarabine. One patient showed only a slight decrease of immunoglobulin (Ig) M (from 5,750 mg/dl to 4,700 mg/dl) and no improvement of anemia. Therefore, treatment was stopped after three cycles. In the other six patients, a marked reduction of IgM levels (from 6,140 mg/dl to 1,220 mg/dl median), a normalization of hemoglobin (from 10.8 g/dl to 12.3 g/dl median), a reduction of lymphocyte count (from 1992/>microl to 652/microl median), and a reduction of beta2 microglobulin (from 2.3mg/l to 1.8 mg/l median) were achieved. A 50% IgM reduction was achieved 5.4 months (median) after the beginning of therapy, and the maximum response was observed 17.3 months (median) after the end of treatment. The responses were sustained without further therapy in six patients for 20.8-55.2 months. In one patient, disease progression was observed 12.5 months after the end of therapy. Fludarabine therapy was well tolerated with few side effects. In three patients, febrile episodes occurred. No opportunistic infections were recorded. We conclude that fludarabine is an effective treatment in previously untreated or in minimally pretreated patients with Waldenström's macroglobulinemia.

Adult↗
PubMed2000

Treatment of patients with advanced chronic myelogenous leukemia with interferon-alpha-2b and continuous oral cytarabine ocfosfate (YNK01): a pilot study.

The efficacy of continuous oral cytarabine ocfosfate (YNK01) (300 mg/day) in combination with interferon alpha (IFNalpha, 5x10(6) IU/day) was evaluated in patients with advanced chronic myelogenous leukemia, who previously failed to respond to IFNalpha-based therapies. Dose escalations up to 900 mg YNK01 were allowed in patients who failed to respond. In view of our results, four patients developed a complete hematological response after YNK01 was started. Among those who initially responded to YNK01, one complete cytogenetic response was achieved 18 months later. Although the data are preliminary, this is the first study showing that continuous administration of YNK01 along with IFNalpha is effective in patients with advanced chronic myelogenous leukemia.

Adult↗
PubMed2000

Reciprocal translocation (3;5)(q26;q22) and possible BCHE gene involvement in an unusual myelogenous disorder with both myeloproliferative and dysplastic features.

We report on a 77-year-old male patient who presented with an unusual myelogenous disorder exhibiting both myeloproliferative and dysplastic features. The patient suffered from leukocytosis, eosinophilia, basophilia, transfusion dependent anemia, and rapidly progressing thrombocytopenia. Classical chromosome analysis and fluorescence in situ hybridization (FISH) revealed a reciprocal t(3;5)(q26;q22). Using yeast artificial chromosome (YAC) probes, the breakpoint on chromosome 3 was localized to the butyrylcholinesterase (BCHE) gene (3q26.1-q26.2). This gene has recently been implicated in the regulation of myeloid cells. Whether the BCHE gene was also involved in the deregulation of myelopoiesis, causing the unusual clinical picture in this case, remains unknown.

Aged↗
PubMed2000

1,25-Dihydroxyvitamin D(3) inhibits dendritic cell differentiation and maturation in vitro.

OBJECTIVE: Because of its potent immunosuppressive properties in vitro as well as in vivo, we studied the effect of 1,25-dihydroxyvitamin D(3) (calcitriol) on differentiation, maturation, and function of dendritic cells (DC). MATERIALS AND METHODS: Monocyte-derived DCs were generated with GM-CSF plus IL-4, and maturation was induced by a 2-day exposure to TNFalpha. DCs were derived from CD34(+) progenitors using SCF plus GM-CSF plus TNFalpha. For differentiation studies, cells were exposed to calcitriol at concentrations of 10(-)(9)- 10(-7) M at days 0, 6, and 8, respectively. The obtained cell populations were evaluated by morphology, phenotype, and function. RESULTS: When added at day 0, calcitriol blocked DC differentiation from monocytes and inhibited the generation of CD1a(+) cells from progenitor cells while increasing CD14(+) cells. Exposure of immature DCs to calcitriol at day 6 resulted in a loss of the DC-characteristic surface molecule CD1a, downregulation of the costimulatory molecules CD40 and CD80, and MHC class II expression, whereas the monocyte/macrophage marker CD14 was clearly reinduced. In addition, calcitriol hindered TNFalpha-induced DC maturation, which is usually accompanied with induction of CD83 expression and upregulation of costimulatory molecules. In contrast, the mature CD83(+) DCs remained CD1a(+)CD14(-) when exposed to calcitriol. The capacity of cytokine-treated cells to stimulate allogeneic and autologous T cells and to take up soluble antigen was inhibited by calcitriol. CONCLUSION: The potent suppression of DC differentiation, the reversal of DC phenotype, and function in immature DCs, as well as the inhibition of DC maturation by calcitriol, may explain some of its immunosuppressive properties.

Antigens, CD↗
PubMed2000

Drug resistance factors in acute myeloid leukemia: a comparative analysis.

To compare the clinical relevance of drug resistance factors in de novo acute myeloid leukemia (AML), we determined their relationship to both response to induction chemotherapy and survival of the patients in univariate as well as multivariate analyses. The drug resistance factors immunocytochemically studied in 111 patients at the time of diagnosis included the lung resistance protein (LRP), P-glycoprotein (P-gp), multidrug resistance protein (MRP1) and bcl-2. In the univariate analyses, age (P = 0.005), karyotype (P = 0.03), LRP (P = 0.003), P-gp (P = 0.02) and bcl-2 (P = 0.03) predicted for response to induction chemotherapy, whereas MRP1 had no predictive value. Age (P = 0.05), karyotype (P = 0.05) and LRP (P = 0.03) retained their predictive value in the multivariate logistic regression analyses. With regard to overall survival, age (P = 0. 008), karyotype (P = 0.006), LRP (P = 0.001) and P-gp (P = 0.01) were of prognostic value in the univariate Cox regression analyses but only age (P = 0.01), karyotype (P = 0.02) and LRP (P = 0.01) retained their prognostic significance in the multivariate analyses. A risk score based on the number of independent prognostic factors allowed division of patients into four groups with different outcome. In these groups, the complete remission rates were 93%, 75%, 47% and 33%, respectively, and median overall survival was 2.4, 1.2, 0.6 and 0.2 years, respectively. Thus, several drug resistance factors did predict outcome in the univariate analyses but LRP was the only drug resistance factor with independent predictive and prognostic significance. The proposed risk score might be useful for risk-adapted treatment in the future. Leukemia (2000) 14, 68-76.

Acute Disease↗
PubMed2000

Prognosis of patients with a second relapse of acute myeloid leukemia.

Recurrence of the disease is the major problem in the treatment of acute myeloid leukemia (AML). The majority of patients who achieve a second remission will ultimately relapse. In this retrospective single-center study, we have analyzed the outcome of patients with a second relapse and tried to define the prognostic factors in intensively treated patients. Of 534 patients with AML, 62 had a second relapse. Thirty-three received further intensive chemotherapy (CT). Eighteen patients (55%) achieved a third complete remission (CR). The early death (ED) rate was only 9%. The overall survival (OS) of treated vs untreated patients was 6.9 vs 1.3 months, respectively (P = 0.01). The major selection criteria for a third CT were a favourable (t(15;17),t(8;21),inv(16)) or normal karyotype, long (>11 months) second CR (P < or = 0.005) and no previous bone marrow transplantation (BMT)(P < 0.01). Favorable or normal karyotype, second CR >11 months, as well as no previous BMT (P < 0.01) were associated with the achievement of a third CR. Favorable (P < 0.005) or normal karyotype (P < 0.01), as well as a second CR >11 months (P < 0.005) were associated with prolonged survival after CT. The median OS for patients receiving CT with favorable or normal cytogenetics, a second CR > 11 months, but no previous BMT was 26.5 months. Five patients with favorable or normal karyotype achieved a fourth or fifth remission. We conclude that intensive CT is associated with a survival benefit and good quality of life if patients are properly selected.

Acute Disease↗
PubMed2000

Kell is not restricted to the erythropoietic lineage but is also expressed on myeloid progenitor cells.

Anti-Kell antibodies have been shown to suppress fetal erythropoiesis, but little is known about their effect on myelopoiesis. We analysed the effect of Kell-related antibodies on granulocyte-macrophage colony-forming units (CFU-GM) growth in semisolid medium using peripheral blood mononuclear cells (PBMNCs) from haematologically normal individuals. In addition to its inhibitory effect on erythroid burst-forming units (BFU-E) growth, anti-Kell antibodies significantly reduced CFU-GM colony formation from Kell-positive individuals but not from Kell-negative donors. Moreover, anti-cellano and anti-Kpb antibodies also inhibited the growth of CFU-GM from antigen-positive MNCs. These data indicate that Kell is not restricted to erythroid blood cells, but is also expressed on myeloid progenitor cells.

Antibodies↗
PubMed2000

Quantitative determination of total coliforms and Escherichia coli in marine waters with chromogenic and fluorogenic media.

This study compared the performance of LMX(R) broth (LMX), Chromocult Coliform(R) agar (CC) and Chromocult Coliform agar plus cefsulodin (10 microg ml-1) (CC-CFS), with standard methods multiple tube fermentation (MTF), for the enumeration of total coliforms and Escherichia coli from marine recreational waters. LMX and CC are two media designed to concurrently detect total coliform (TC) bacteria and E. coli by the specific action of beta-galactosidase (total coliforms) and beta-glucuronidase (E. coli). Overall results for the TC test showed that LMX, CC and MTF recovered 2.63, 1.95 and 1.90 times as many TCs as CC-CFS, respectively. Data from the multiple range test showed significant differences (P < 0.05) between TC counts on CC-CFS and LMX. The traditional MTF was less sensitive for E. coli enumeration. However, there was no statistically significant differences between LMX, CC, CC-CFS and the MTF method for E. coli enumeration. Background interference was reduced on CC-CFS and the counts obtained reflected more accurately the number of TCs. Therefore, the contribution of beta-galactosidase positive, non coliform bacteria (Aeromonas spp. and Vibrio spp.) to TC counts should not be neglected.

Bacteriological Techniques↗
PubMed2000

Generation of dendritic cells from human chronic myelomonocytic leukemia cells in fetal calf serum-free medium.

It is generally believed that the immune system plays a role not only in the acquisition of malignant diseases but also in the rejection of microscopic as well as established tumor cells. Failure of the immune system to eliminate tumor cells may be, among other factors, due to an insufficient presentation of tumor antigens. Dendritic cells (DCs), as professional antigen-presenting cells, therefore, may be therapeutically used to initiate or enhance immune responses in patients with malignancies. In this study we demonstrate that peripheral blood cells of patients with chronic myelomonocytic leukemia (CMML) can be induced to acquire DC characteristics. Upon culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4) plus tumor necrosis factor alpha (TNFalpha), CMML cells develop DC morphology and acquire the phenotypic characteristics of DCs. When a CD14+ cell population is used for DC generation, a homogeneous differentiation towards the DC lineage occurs similar to that, observed in normal peripheral blood monocytes. CMML-derived DCs are potent stimulators of the allogeneic mixed lymphocyte reaction (MLR) when compared with uncultivated cells. The demonstration of a deletion of the long arm of chromosome 7, del(7)(q22), in 86% of highly enriched CD1a+ cells by fluorescence in situ hybridization (FISH) indicates the leukemic origin of generated DCs. In addition, we present data that generation of CMML-derived DCs is also possible under fetal calf serum-free conditions for a potential clinical use. These DCs may be used as a cellular vaccine to induce anti-tumor immunity in patients with CMML.

Cell Differentiation↗