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Biomedical subjects

K Geissler

Publications and source records attributed to K Geissler.

At least 109 records · Page 6Linked to original sources
PubMed1994

High efficacy of the German multicenter ALL (GMALL) protocol for treatment of adult acute lymphoblastic leukemia (ALL)--a single-institution study.

Sixty-one consecutive patients with acute lymphoblastic leukemia (ALL) (B-ALL excluded) were treated with the protocol described by Hoelzer et al. [15]. The complete remission (CR) rate was 85% (52/61 patients). Three patients died during induction therapy; six patients were refractory to treatment. The median duration of continuous complete remission (CCR), disease-free survival (DFS), and overall survival was 41.5, 41.4, and 40.8 months, respectively. At 5 years the probability of CCR was 49%, of DFS 43.5%, and of overall survival 41.6%. In the univariate analysis older age (> 35 years, p = 0.01), bcr-abl positivity (p = 0.007), and time to CR (> 4 weeks, p = 0.05) were significantly unfavorable prognostic factors. In the multivariate analysis only age (p = 0.006) and time to CR (p = 0.02) remained significant. Thus, our data confirm the high efficacy of this treatment regimen with regard to CR rate and remission duration.

Adolescent↗
PubMed1994

Detection of trisomy 12 in chronic lymphocytic leukaemia: comparison of a polymerase chain reaction based technique with fluorescence in situ hybridization.

Trisomy 12 is the most frequent chromosomal aberration in chronic lymphocytic leukaemia (CLL) and seems to indicate a poor prognosis. To detect this abnormality we tested the applicability of the polymerase chain reaction (PCR) and compared it to the current standard fluorescence in situ hybridization (FISH). Two DNA regions containing variable numbers of tandem repeats (VNTR) located on (a) the long and (b) the short arm of chromosome 12 were chosen for PCR analysis. 8/72 patients (11%) were trisomy 12 positive compared to 16% by FISH. Chromosomal imbalances were only detected by PCR if at least 20% of the cells carried the numerical aberration.

Chromosomes, Human, Pair 12↗
PubMed1994

[Therapy of Hodgkin's disease].

Hodgkin's disease has become the prototype of a curable neoplastic condition. In localized disease (stages I and II) cure can be achieved with radiotherapy alone unless B-symptoms are present. In case of B-symptoms or generalized disease (stages III and IV) the administration of polychemotherapy is mandatory. In advanced stages combinations of the non-cross-resistant regimens MOPP and ABVD seem to be the most effective. In patients relapsing from the MOPP/ABVD or MOPP/ABV regimen salvage chemotherapy offers a chance of remission but not cure. Such patients, in particular those with a short first remission, are candidates for autologous stem cell transplantation which can still induce durable remissions in a subset of patients. Considering the long term complications such as infertility and the development of secondary neoplasms one has to carefully balance the benefits against the potential risks of the initial treatment approach.

Combined Modality Therapy↗
PubMed1993

Monocytes do not make mast cells when cultured in the presence of SCF. Characterization of the circulating mast cell progenitor as a c-kit+, CD34+, Ly-, CD14-, CD17-, colony-forming cell.

Mast cells (MC3) belong to the hemopoietic system and arise from hemopoietic precursor cells. Human MC progenitors can be detected in the bone marrow as well as in the peripheral blood (pb) and are responsive to the mast cell growth factor SCF, the ligand of the c-kit tyrosine kinase receptor. However, little is known about the subsets of cells that become committed to and differentiate into mature human MC. In this study, the identity of the circulating MC progenitor, previously felt to be a monocyte (Mo) or basophil (Ba), was investigated. For this purpose, CD14+ pb monocytes, CD17+ pb basophils and CD34+ cord blood cells were purified to homogeneity (> 95%) from mononuclear cells (normal adult donors, n = 17, cord blood, n = 2) by counter-flow centrifugation followed by cell sorting with mAb. In the presence of rhSCF, MC developed in long term suspension culture from pure CD34+ cells but not from pure Mo, pure Ba, or Ly (MC-tryptase levels on day 42: CD14+ Mo: 3.7 +/- 0.8 vs CD17+ Ba: 3.2 +/- 0.5 vs Ly: 2.0 +/- 1.5 vs control: 196.5 +/- 92.5 ng/ml, p < 0.001). Depletion of CD34+ cells from MNC resulted in a loss of MC in long term suspension culture, whereas depletion of either Mo, Ba, or Ly did not. In methyl-cellulose cultures in the presence of rhSCF, MC and tryptase could be detected in pure (CFU-mast) and mixed (CFU-myeloid/mast) MC colonies. Together, MC do not originate from circulating Mo, Ba, or Ly. The circulating MC progenitor is a CD34+, c-kit+, Ly-, CD14-, CD17- colony-forming cell. This is the first definitive demonstration that mast cells are replenished directly from early hemopoietic progenitors and thus form a unique cell lineage within the hemopoietic system.

Antigens, CD↗
PubMed1993

Recombinant human leukemia inhibitory factor induces acute phase proteins and raises the blood platelet counts in nonhuman primates.

Recombinant human leukemia inhibitory factor (rhLIF) produced by Escherichia coli was administered subcutaneously (sc) to rhesus monkeys at doses of 2, 10, and 50 micrograms/kg body weight/d for 14 days to assess its biologic activities in vivo. Serum levels of positively regulated acute phase proteins (APP) (C-reactive protein, alpha 1-antitrypsin, haptoglobin, and ceruloplasmin) were increased, whereas the negatively regulated APP prealbumin decreased in response to rhLIF treatment. During the second week of treatment, blood platelet counts began to increase, resulting in a maximum of a twofold increase above normal levels a week after termination of the rhLIF treatment. No changes were seen in total and differential white blood cell counts in blood progenitor levels and in red blood cell numbers. The low- and medium-dose rhLIF treatments were tolerated without significant side effects. The animals treated with the high dose showed a reduction in body weight of approximately 10%. In conclusion, rhLIF was shown to stimulate APP and to increase the number of platelets in circulation in nonhuman primates.

Acute-Phase Proteins↗
PubMed1993

Granulocyte colony-stimulating factor (G-CSF) as an adjunct to induction chemotherapy of adult acute lymphoblastic leukemia (ALL).

Our purpose was to evaluate the ability of recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) as an adjunct to induction chemotherapy of acute lymphoblastic leukemia (ALL) to ameliorate chemotherapy-induced neutropenia and thus allow patients to receive full doses of chemotherapy on time. Sixteen consecutive patients with adult ALL (13 de novo, three relapsed) were treated with induction chemotherapy according to the BMFT protocol and received in addition r-metHuG-CSF (200 micrograms/m2/day). Patients who were treated with the same induction chemotherapy but without G-CSF between 1982 and 1990 served as controls. Fifteen of the 16 patients achieved complete hematological remission. One patient died because of fungal septicemia. Compared with historical controls, G-CSF-treated patients had a significantly faster neutrophil recovery in phase I, resulting in neutrophil counts > 1000/microliters at day 17 vs day 26 (in median) in controls. In phase II, the onset of severe leukocytopenia (< 1500/microliters) was significantly (p = 0.01) delayed and the degree of leukocytopenia less pronounced (mean nadir 3300/microliters) in G-CSF-treated patients compared with controls (1880/microliters). The number of days of febrile neutropenia was not different in phase I. In phase II it was lower in study patients (0 vs 1.1 days), but the difference did not reach statistical significance (p = 0.09). Full doses of chemotherapy could be given on time to 11/13 (85%) G-CSF patients but to only 7/30 (23%) controls. These data indicate that (a) G-CSF can be given along with chemotherapy in induction treatment of ALL without compromising efficacy; (b) the duration of neutropenia in phase I is markedly shortened and the degree of leukocytopenia in phase II ameliorated; (c) these beneficial effects allow patients to receive full doses of chemotherapy on time.

Adolescent↗
PubMed1993

Granulocyte colony-stimulating factor (rh G-CSF) as an adjunct to interferon alpha therapy of neutropenic patients with hairy cell leukemia.

Six patients with hairy cell leukemia (HCL) and neutropenia (median neutrophil count 563/microliters, range 30-1200) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) at a dose of 5 micrograms/kg by daily subcutaneous injection as an adjunct to interferon-alpha (IFN-a) therapy, in order to ameliorate neutropenia. Five of six patients responded to G-CSF with normalization of neutrophil counts (> 1800/microliters) within 2-11 days and a median neutrophil count of 5211/microliters (range 4312-10160) at the end of G-CSF therapy. In three of these patients, infections resolved when neutropoiesis recovered. In one patient with very severe neutropenia (30/microliters), in whom myeloid progenitors were not detectable, G-CSF therapy failed to restore granulopoiesis. Cessation or interruption of G-CSF after 2-5 weeks of therapy resulted in a rapid decline of neutrophil counts to lower or subnormal levels (median value 1478/microliters, range 770-2739) within 1 week, suggesting that the improvement of granulopoiesis was dependent on G-CSF and not due to IFN-a therapy. G-CSF may be a useful adjunct to IFN-a therapy in patients with HCL in order to manage or prevent neutropenic complications in the early phase of treatment.

Adult↗
PubMed1993

Treatment of drug-induced agranulocytosis with recombinant granulocyte colony-stimulating factor (rh G-CSF).

Five patients with drug-induced agranulocytosis received 300 micrograms recombinant human granulocyte colony-stimulating factor (rh G-CSF) subcutaneously twice daily for 2-5 days. G-CSF therapy resulted in a steep increase of the neutrophil count, which was faster than that in patients with spontaneous recovery reported in the literature. In all four patients with infectious complications fever rapidly declined with the increase of granulocytes. G-CSF may be useful in the management of drug-induced agranulocytosis.

Adult↗
PubMed1993

Tetrasomy 8 in acute monoblastic leukemia (AML-M5a) with myelosarcomatosis of the skin.

We report a new case with isolated tetrasomy 8, an 82-year-old female patient in whom multiple disseminated nodular skin infiltrations up to 5 cm in diameter preceded acute monoblastic leukemia (AML-M5a). Despite an initial response to chemotherapy and radiotherapy, the patient died 1 year after diagnosis of relapsed leukemia. To assess the size of the tetrasomic clone, fluorescence in situ hybridization (FISH) analysis with a centromere-specific chromosome 8 probe was performed. Seventy percent of interphase cells showed four signals and 22% showed three signals. Because this trisomic clone was not detected by conventional cytogenetics, tetrasomic cells may have a proliferation advantage in vitro. Whether tetrasomy 8 arises from a simultaneous mitotic nondisjunction of both chromosomes 8 during one cell division or evolves secondarily from trisomy 8 through a second mitotic error is not known. Alternatively, trisomy 8 may originate from tetrasomy 8 by loss of one chromosome 8.

Aged↗
PubMed1993

[Mobilization of circulating hematopoietic stem cells by granulocyte colony stimulating factor after chemotherapy in multiple myeloma].

Due to the relatively low tumour cell contamination of peripheral blood in patients with multiple myeloma, autologous transplantation of circulating stem cells may have theoretical advantages over autologous bone marrow transplantation. In four patients with multiple myeloma who where considered potential candidates for autologous stem cell transplantation G-CSF (600 micrograms/day) was administered following chemotherapy in order to maximally increase the number of circulating progenitor cells during haematopoietic rebound and to facilitate progenitor cell harvest by leukapheresis. In two previously untreated patients the administration of G-CSF following chemotherapy according to the UVA protocol (ultralan, vincristine, adriamycin) greatly increased circulating haematopoietic stem cells from 247 to 7552 CFU-GM/ml in patient 1 and from 173 to 6361 CFU-GM/ml in patient 2, which by far exceeded the increase in progenitor cells following chemotherapy alone, namely only to 594 and 317 CFU-GM/ml in patient 1 and patient 2, respectively. In two repeatedly pretreated patients, the combination of UVA and G-CSF was much less effective. Progenitor cells increased from 144 to 735 CFU-GM/ml in patient 3 and only from 222 to 232 CFU-GM/ml in patient 4. In both cases, however, mobilization of haematopoietic progenitor cells by G-CSF following cyclophosphamide (50 and 70 mg/kg body weight, respectively) led to much higher CFU-GM peak values (5324 in patient 3 and 2245 in patient 4), thus allowing an adequate harvest of mononuclear cells and CD 34+ cell numbers to achieve, in all probability, the prompt and complete reconstitution of haematopoiesis in case of transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1993

Potentiation of GM-CSF or G-CSF induced mobilization of circulating progenitor cells by pretreatment with IL-3 and harvest by apheresis.

Recombinant human colony-stimulating factors (CSFs) are increasingly used for mobilizing progenitor cells in the peripheral blood (PB). 7 patients were treated with GM-CSF or G-CSF at a dose of 5 micrograms/kg/d for 5 days and after a treatment free interval received another cycle of the same cytokine after pretreatment with IL-3. Pretreatment with 5 micrograms/kg/d of IL-3 for 7 days did not mobilize by itself but significantly potentiated GM-CSF or G-CSF induced mobilization of PB progenitor cells in all 5 patients tested. As compared to the mobilization capacity of GM-CSF or G-CSF alone, 7 day IL-3 pretreatment potentiated maximum values of CFU-GM by 3.7-6.3 fold in patients receiving GM-CSF (n = 2) and by 1.8-3.3 fold in patients receiving G-CSF leading to a 10-23 fold increase in numbers of circulating CFU-GM by the combination IL-3/GM-CSF, and a 26-101 fold increase by IL-3/G-CSF, respectively. Stem cell apheresis in patients treated with IL-3 + G-CSF or GM-CSF yielded enough PB-stem cells to ensure complete engraftment after ablative chemotherapy.

Blood Component Removal↗
PubMed1993

[Collection and long-term preservation of peripheral stem cells].

The methods of collection and storage of peripheral blood stem cells are described and the harvesting after conditioning with cytokines and/or myelosuppressive therapy is discussed. It could be demonstrated that the combination of cytostatics and cytokines gives the best yield and enables to collect a sufficient amount of peripheral blood stem cells for a successful engraftment after myeloablative therapy with only few aphereses.

Antigens, CD↗
PubMed1992

Induction of differentiation of human mast cells from bone marrow and peripheral blood mononuclear cells by recombinant human stem cell factor/kit-ligand in long-term culture.

In the murine system, a number of cytokines (including interleukin-3 [IL-3], IL-4, and stem cell factor [SCF]) promote the growth of mast cells (MCs). However, so far little is known about factors controlling differentiation of human MCs. Recent data suggest that human MCs express receptors (R) for SCF. The aim of the present study was to investigate whether recombinant human (rh) SCF induces differentiation of human MCs from their precursor cells. For this purpose, bone marrow (BM; normal donors, n = 6) and peripheral blood (PB; normal donors, n = 11) mononuclear cells (MNC) were cultured in the presence of rhSCF, rhIL-3, rhIL-4, rhIL-9, recombinant human macrophage colony-stimulating factor (rhM-CSF), or control medium in long-term (8 weeks) suspension cultures. After 4 weeks, up to 5% of the MNC (BM and PB) cultured in the presence of rhSCF, but not in the presence of other cytokines, were found to exhibit the characteristics of MCs. These MCs expressed the YB5.B8-reactive domain of the SCF R as well as IgE R, as determined by combined toluidine blue/immunofluorescence staining. Myeloid antigens, likewise expressed on human basophils (ie, CD11b, CDw65, and Bsp-1), could not be detected on these cells. Furthermore, rhSCF, but not rhIL-3, rhIL-4, rhIL-9, or rhM-CSF, induced dose- and time-dependent increases in the formation of cellular tryptase (an MC-specific enzyme) (rhSCF [100 ng/mL], 1,308 +/- 679 ng/mL v control medium, 18 +/- 6 ng/mL tryptase on day 35 of PB cell cultures), as well as an increase in cellular histamine. After 6 to 8 weeks, when other mature hematopoietic cells decreased, MCs still could be detected in culture, with up to 40% of all cells being MCs. To test whether rhSCF also activates tissue MCs, we performed histamine release experiments (dispersed tissue; lung, n = 3; uterus, n = 3). SCF was found to enhance (by up to 3.4-fold) the capacity of the MCs to release histamine upon cross-linkage of IgE R with anti-IgE. Together, these observations suggest that rhSCF induces in vitro differentiation of human MCs from their BM and PB precursor cells in long-term culture and upregulates MC releasability.

Antibodies, Monoclonal↗
PubMed1992

Type beta transforming growth factors promote interleukin-3 (IL-3)-dependent differentiation of human basophils but inhibit IL-3-dependent differentiation of human eosinophils.

Basophils and eosinophils share a common differentiation pathway. Factors regulating terminal commitment toward one cell type, however, have so far not been defined. Interleukin-3 (IL-3) is a potent differentiation factor for both human eosinophils and basophils. In the present study, the effects of various recombinant human (rh) growth regulators on IL-3-dependent growth of eosinophils and basophils were studied in a bone marrow (BM) suspension culture system (normal donors, n = 13). We found that type beta transforming growth factors (TGFs) lead to a significant increase in the absolute numbers of basophils in BM cultures grown in the presence of IL-3 (day 14 of culture; IL-3: 133 +/- 20 v IL-3 + TGF-beta 1: 231 +/- 28 x 10(3)/mL [P less than .01]) and to an increase in the total histamine values (IL-3: 72.6 +/- 22.2 v IL-3 + TGF-beta 1: 142.9 +/- 37.3 ng/mL [P less than .015]) compared with rhIL-3 alone. In contrast, type beta TGFs were found to inhibit the IL-3-dependent growth of eosinophils (IL-3: 170.4 +/- 37.2 v IL-3 + TGF-beta 1: 16.7 +/- 5.2 x 10(3)/mL [P less than .01]) and formation of eosinophil cationic protein in the same culture system. The effect of TGF-beta 1 (and TGF-beta 2) on IL-3-dependent differentiation of basophils and eosinophils was dose- and time-dependent (maximum effects observed with 1 to 10 ng/mL of rhTGF-beta 1 or TGF-beta 2) and could be neutralized by an antibody specific for TGF-beta 1. In contrast to the TGFs, interferon-alpha (IFN-alpha) and IFN-gamma were found to downregulate IL-3-dependent formation of both basophils (IL-3: 167 +/- 33 v IL-3 + IFN-alpha: 67 +/- 25 v IL-3 + IFN-gamma: 65 +/- 33 x 10(3)/mL [P less than .01]) and eosinophils (IL-3: 239 +/- 5 v IL-3 + IFN-alpha: 81 +/- 4 v IL-3 + IFN-gamma: 67 +/- 17 x 10(3)/mL [P less than .05]) in our culture system. Type beta TGFs as well as the IFNs failed to directly induce differentiation of human basophils or eosinophils in the absence of other growth factors. Together, these results show that type beta TGFs and IFNs are potent regulators of cytokine-dependent growth and differentiation of human allergic effector cells.

Antibodies, Monoclonal↗