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Biomedical subjects

A Ganser

Publications and source records attributed to A Ganser.

At least 235 records · Page 13Linked to original sources
PubMed1990

[Effects on bone marrow during stimulation of hematopoietic stem cells with recombinant human interleukin-3].

Bone marrow aspirates and biopsies of 20 patients with malignant tumors (n = 6), bone marrow failure due to chemotherapy (n = 4), myelodysplastic syndromes (n = 5) and aplastic anemia (n = 5) were analysed before and after treatment with recombinant human interleukin-3. rhIL-3 led to increased overall bone marrow cellularity with trilinear stimulation of hematopoietic cells. In all patients marked eosinophilia and, in some, fibrosis was observed. These results show that rhIL-3 stimulates the proliferation and differentiation of pluripotent hematopoietic progenitor cells and may contribute to the treatment of bone marrow failure.

Anemia, Aplastic↗
PubMed1990

[In vitro and in vivo effects of recombinant human interleukin-3 on hematopoietic progenitor cells].

As part of a phase I/II clinical trial with recombinant human Interleukin-3 (rhIL-3), bone marrow and peripheral blood cells from patients treated with rhIL-3 were assessed in vitro for effects on the cycling status and frequencies of erythroid, myelomonocytic and multilineage progenitor cells. Treatment with rhIL-3 induced a pronounced increase in S-phase rate of BFU-E, CFU-GEMM and day 14 CFU-GM. Circulating CFU-GEMM and day 14 CFU-GM were increased on day 7 of therapy whereas circulating BFU-E were reduced in the majority of patients. After i.v. bolus injection of IL-3 an acute effect on the peripheral blood count with neutrophilia and, after an initial nadir, monocytosis was observed. IL-6 serum-levels increased in 5 out of 14 patients after IL-3 administration with concomitant side effects in 2 patients in whom IL-6 levels increased above 75 pg/ml. In the majority of the patients a stimulation of peripheral leukocytes and platelets was observed during the 15 day treatment course. In conclusion rhIL-3 induces a multilineage response in vivo by stimulating proliferation of hemopoietic progenitor cells with a resulting elevation in peripheral blood counts.

Bone Marrow↗
PubMed1990

Stimulation of granulopoiesis in patients with malignancy by recombinant human granulocyte-macrophage colony-stimulating factor: assessment of two routes of administration.

We administered Escherichia coli-derived recombinant human granulocyte-macrophage colony-stimulating factor to 61 patients with malignancy, 36 of whom had normal peripheral blood counts and 25 of whom had peripheral cytopenia due to underlying bone marrow disease, to compare the efficacy of two different routes of administration to stimulate the in vivo granulopoiesis: i.e., continuous i.v. infusion and s.c. injection. Three well-tolerated dose levels were investigated. Application of granulocyte-macrophage colony-stimulating factor resulted in dose-dependent increases in circulating neutrophils, eosinophils, and monocytes and an increase in bone marrow cellularity, irrespective of route of administration. In some patients, mild side effects, including bone pain, dyspnea, flu-like symptoms, and a decrease of platelet counts, were recorded, but they were less pronounced when the hormone was administered subcutaneously.

Adolescent↗
PubMed1990

Effects of recombinant human IL-7 on blast cell proliferation in acute lymphoblastic leukemia.

We investigated the effects of interleukin-7 (IL-7), a stromal cell derived cytokine known to stimulate proliferation of murine lymphoid precursor cells, alone and in combination with IL-3, IL-1, and IL-6 on proliferation of purified blast cells in acute lymphoblastic leukemia (ALL). After 7 days of liquid culture DNA-synthesis was induced in six of 10 cALL, three of five B-ALL, and two of seven T-ALL samples by IL-7 or IL-3 or both. Monitoring of leukemic cell populations in suspension culture by Southern blot analysis of immunoglobulin and T cell receptor gene rearrangements revealed preferential stimulation of the leukemic cell clone by both IL-7 or IL-3 in one cALL and one B-ALL sample. In these cases the combination of IL-7, IL-3, and IL-1 was as effective in stimulation of DNA-synthesis as the most potent cytokine alone. There was no evidence of lymphoid maturation during liquid culture as defined by immunophenotyping using flow cytometry. Stimulation of nonleukemic cell population seen in two other cases of cALL was associated with residual erythroid and granulocyte-macrophage colony forming cells after liquid culture as defined in parallel clonogenic assays in one and detection of CD 33+ and CD 13+ cells after culture in the other cALL sample. We conclude that IL-7 directly stimulates monoclonal growth of leukemic cells in a subset of ALL without evidence of concurrent maturation induction.

Adolescent↗
PubMed1989

The effect of recombinant human granulocyte-macrophage colony-stimulating factor on neutropenia and related morbidity in chronic severe neutropenia.

STUDY OBJECTIVE: To define the clinical and hematologic effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on patients with chronic severe neutropenia. DESIGN: Open-label, phase II study of rhGM-CSF. SETTING: Inpatient hematology and surgery clinic at a university medical center. PATIENTS: Four consecutive patients with chronic severe neutropenia, which in two cases was complicated by severe infection, in one case by perianal fistula, and in one case by complete rectal prolapse. Two patients had chronic idiopathic neutropenia; one patient had congenital neutropenia (myelokathexis); and one patient had autoimmune neutropenia. INTERVENTIONS: The rhGM-CSF was given intravenously or subcutaneously at starting dosages of 150 to 1000 micrograms/m2 body surface area.d for 12 to 14 consecutive days. Two patients received a second course of daily rhGM-CSF treatment after a nontreatment interval of 14 to 20 days. MEASUREMENTS AND MAIN RESULTS: In all four patients, the absolute neutrophil counts increased from less than 0.25 x 10(9)/L to 3.2 to 19.2 x 10(9)/L within 2 weeks of beginning rhGM-CSF therapy. Two patients had life-threatening infections that resolved during therapy. The two other patients had major ano-rectal surgery during rhGM-CSF treatment and had no postoperative infections. CONCLUSIONS: In patients with chronic neutropenia, rhGM-CSF may increase neutrophil counts. This therapy may be a useful adjunct to antibiotic therapy for patients with infection and perioperatively for patients having anorectal surgery.

Adult↗
PubMed1989

Recombinant human granulocyte-macrophage colony-stimulating factor and low-dose cytosine arabinoside in patients with myelodysplastic syndrome. A pilot study.

In a pilot study, five patients with myelodysplastic syndromes with an excess of blast cells were treated with a combination of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and low-dose cytosine-arabinoside (ara-C) in an attempt to selectively kill the leukemic blast cells and thereby to restore normal hemopoiesis. The treatment schedule consisted of three 14-day-cycles of 250 micrograms/m2 rhGM-CSF and 20 mg/m2 ara-C given daily s.c. with four-week treatment-free intervals. In all four evaluable patients the percentage of bone marrow blast cells decreased significantly with an increase in the mature myeloid cells but without bone marrow aplasia. Toxic side effects attributable to the drugs were minor with fever, mild bone pain, erythema and itching at the site of subcutaneous injection of rhGM-CSF. In conclusion, the combined therapy of rhGM-CSF and low-dose ara-C appears to be effective in the short-term control of the leukemic cell population.

Adult↗
PubMed1989

[Effect of tumor necrosis factor on human hematopoietic precursor cells].

The effect of human recombinant tumor necrosis factor (rhTNF-alpha) on the in vitro colony growth of normal hematopoietic progenitor cells was investigated. In a clonal colony-assay a dose-dependent inhibition of erythroid BFU-E, granulocyte/monocyte CFU-GM and megakaryocyte CFU-Mk was demonstrated. CFU-Mk were completely inhibited by low doses of TNF-alpha (3 U-300 U/ml). 50% inhibition occurred at 10 U/ml of TNF for CFU-Mk, 100% inhibition at 300 U/ml of TNF. 50% inhibition occurred at 233 U/ml of TNF for CFU-GM, and 100% inhibition for CFU-GM was not observed. For inhibition of BFU-E higher doses of TNF-alpha were necessary (100 U-1,000 U/ml). The growth inhibitory effect could selectively be abolished by antibodies against TNF-alpha. Removal of adherent cells and T-lymphocytes from the bone marrow cells had no significant influence of the suppressive effect of TNF-alpha. The inhibitory effect of TNF-alpha is due to a direct action on hematopoietic progenitor cells and not mediated by accessory cells.

Adult↗
PubMed1989

Prethymic phenotype and genotype of pre-T (CD7+/ER-)-cell leukemia and its clinical significance within adult acute lymphoblastic leukemia.

Pretreatment blast cells from 739 adults with acute lymphoblastic leukemia (ALL) were immunophenotyped as part of a prospective treatment protocol study. Among 192 patients (26%) with T lineage ALL, 47 (6%; 24% of T lineage ALL) had lymphoblasts without sheep erythrocyte rosette formation, but with pan-T antigen CD7 on the membrane and intracellular CD3 proteins mostly in perinuclear accumulation. The T-cell surface antigens CD5 and/or CD2 and focal acid phosphatase were additional markers of this subgroup traditionally called pre-T ALL, whereas thymocyte antigen CD1 as well as CD4 and CD8 antigens were not expressed. Hematopoietic progenitor cell markers, namely terminal deoxynucleotidyl transferase (TdT), and in part common ALL antigen (CD10), HLA-DR antigens, and/or My-10 (CD34), a unique antigen of marrow cells absent in thymus cells, further characterized this immature T-ALL form of putative prothymocytic phenotype (CD7+/intracellular CD3+/TdT+/My-10+/-/HLA-DR+/-/CD10+/-). The prethymic T cell character was supported by germ-line T-cell receptor beta genes found in 21 of 36 patients analyzed. In five cases only T gamma-chain genes were rearranged. Fifteen patients, however, had rearrangements of both T beta and T gamma genes. Immunoglobulin heavy chain genes were rearranged only in two cases. Pre-T ALL differed significantly from E-rosette+ T-ALL in some presenting clinical features, namely mediastinal mass, lymphoadenopathy, and platelet count, and independently of clinical factors in prognosis (P = .02, median remission duration: 15.7 v 33.5 months, and P = .02, median survival time: 24.6 v 50.7 months). We conclude that ALL classification based solely on T- or B-cell lineage affiliation is not sufficient but needs further subdivision according to relevant maturation stages as exemplified here within the T-cell axis. The putative prethymic T cell progenitor phenotype described might help elucidate the sequence of genetic events that commit normal hematopoietic cells to the T-cell lineage.

Adult↗
PubMed1989

Inhibitory effect of azidothymidine, 2'-3'-dideoxyadenosine, and 2'-3'-dideoxycytidine on in vitro growth of hematopoietic progenitor cells from normal persons and from patients with AIDS.

Therapy of patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) with azidothymidine (AZT) and 2'-3'-dideoxycytidine (ddC) is complicated by severe anemia, neutropenia, and thrombocytopenia, the cause of which is unknown. We therefore tested the effect of AZT, ddC, and an additional 2'-3'-dideoxynucleoside analogue, 2'-3'-dideoxyadenosine (ddA), on the hematopoietic progenitor cells derived from the bone marrow of normal persons and patients with AIDS/ARC. All three substances dose-dependently inhibited the in vitro colony formation of the pluripotent (CFU-GEMM), as well as the erythroid (BFU-E) and granulocyte-macrophage progenitor cells (CFU-GM). The 50% inhibition of normal progenitors by AZT occurred at 0.13 microM for CFU-GEMM, 0.32 microM for BFU-E, and 1.9 microM for CFU-GM, by ddA at 15 microM for CFU-GEMM, 40 microM for BFU-E, and 140 microM for CFU-GM. ddC was the most toxic agent and already inhibited 71% +/- 16% (mean +/- standard error of the mean [SEM]) of CFU-GEMM and 52% +/- 22% of BFU-E at 0.1 microM, whereas the 50% inhibition of CFU-GM was reached at 0.3 microM. Hematotoxicity occurred at concentrations lower than necessary to inhibit the human immunodeficiency virus (HIV), except for ddA, which is 100 times less toxic than AZT whereas its antiviral effect is only 10 times less. The inhibition of progenitor cells from AIDS patients by the 2'-3'-dideoxynucleosides was comparable to normal progenitors, except for a higher sensitivity of AIDS-derived CFU-GEMM and BFU-E to AZT.

AIDS-Related Complex↗
PubMed1989

Recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes--a phase I/II trial.

In a phase I/II study, 11 patients with myelodysplastic syndromes (MDS) and severe transfusion-dependent cytopenia were treated with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to investigate the effects of rhGM-CSF on normal hematopoiesis and leukemic cells. The treatment schedule included dose escalation from 15 micrograms/m2 to 150 micrograms/m2 administered by continuous intravenous (IV) infusion for seven to 14 days and was repeated after a two-week treatment-free interval. The blood leukocyte counts increased dose dependently by 130% to 1,800% in ten patients; a rise of monocytes and eosinophils occurred in seven and six patients, respectively. No sustained increase in reticulocytes or platelets was observed. Lymphocyte counts increased in all patients affecting both T-helper and T-suppressor cells; however, the lymphocytes were not activated as analyzed by the expression of the interleukin-2 receptor. In four of the patients, all with greater than 14% blast cells in the bone marrow, the percentage of bone marrow blast cells increased during treatment with rhGM-CSF. Cytogenetic data indicated induction of both proliferation and differentiation of the leukemic clones by rhGM-CSF. Toxic side effects were minor with slight fever, phlebitis at the infusion site, and bone pain in the minority of patients. In conclusion, rhGM-CSF effectively stimulates hematopoiesis in vivo in patients with myelodysplastic syndromes. However, as the leukemic cell population can be stimulated in patients with a higher initial blast cell count, the combination of rhGM-CSF with other differentiation-inducing or cytotoxic agents has to be considered.

Aged↗
PubMed1989

In vivo effects of recombinant human erythropoietin on circulating human hemopoietic progenitor cells.

Recombinant human erythropoietin (rhEpo), now available, has become increasingly more important for clinical use, e.g., in the treatment of anemia of chronic renal failure, and has been shown to reverse anemia in these patients. When patients with anemia of chronic renal failure were treated with rhEpo at dosages between 40 and 120 U/kg three times per week, the numbers of circulating erythroid burst-forming units (BFU-E) and granulocyte-erythrocyte-macrophage-megakaryocyte colony-forming units (CFU-GEMM) significantly increased during the first week of therapy. In contrast, the incidence of circulating granulocyte-monocyte CFU (CFU-GM) was not significantly altered.

Cell Separation↗
PubMed1988

Effect of human recombinant erythropoietin on human hemopoietic progenitor cells in vitro.

Recombinant human erythropoietin (rhEpo), now available, might become increasingly more important for clinical use, e.g., in the treatment of anemia of chronic renal failure. As a prerequisite of clinical trials, we analyzed the stimulatory and suppressive effects of rhEpo on human hemopoiesis by adding rhEpo to in vitro cultures of nonadherent low-density bone marrow cells obtained from normal persons and from patients undergoing hemodialysis for chronic renal failure. rhEpo was shown to be an effective stimulus for erythroid and multilineage colony formation. The dose-response curve was similar for erythroid progenitors BFU-E from normal controls and patients with chronic renal failure. rhEpo had no effect on megakaryocytic colony formation nor on the megakaryocytic differentiation of multilineage stem cells. Because of a good stimulatory activity on erythroid and multilineage stem cells and lack of toxic effects, rhEpo might be useful in the treatment of certain kinds of anemia.

Bone Marrow↗
PubMed1988

Incidence of lineage promiscuity in acute myeloblastic leukemia: diagnostic implications of immunoglobulin and T-cell receptor gene rearrangement analysis and immunological phenotyping.

Sixty-nine blood or bone marrow samples from both children and adults with acute myeloblastic leukemia (AML) were investigated to elucidate the frequency of immunoglobulin (IG) and T-cell receptor (TCR)-gene rearrangements. Non-germline configuration for the IG heavy chain (h) gene was detected in the specimens of nine patients of various subtypes according to the French-American-British classification (FAB), including FAB M1, M2, M4 and M5. Rearrangement of the IG kappa chain (k) gene was present in one of these cases which simultaneously revealed a rearranged TCR-beta (b) chain gene. In another two AML samples we found TCR-b gene rearrangements, in one case in combination with an IG-h gene rearrangement. IG-h gene rearrangements were detected in 10 cases, in one case in conjunction with an IG-kappa (k) and TCR-b gene rearrangement. A highly significant correlation between the occurrence of DNA rearrangements of the IG-h locus and nuclear staining with the enzyme terminal deoxynucleotidyl transferase (TdT) and surface expression of the CD 19 and CD 34 antigen could be identified: all 10 TdT positive AML samples rearranged IG-h. Similarly, six out of 69 AML samples exhibited surface expression of CD 19, five of these in combination with CD 34 and all of them rearranged the IG-h gene. The one leukemia with TCR-b gene rearrangement only was TdT positive as well, but did not express CD 19 or CD 34. We conclude that IG-h gene is rearranged in a substantial proportion of AML, strongly associated with a specific immunophenotype (TdT+, CD19+, CD34+), whereas TCR-b gene rearrangement appears more rarely. No positive correlation between occurrence of IG-h and TCR-b gene-rearrangements and one AML FAB-subtype was found, although a clustering of M1 and M4 FAB subtypes in the AML group showing reconstructed IG-h gene became evident.

Adult↗
PubMed1988

Induction of myeloperoxidase in five cases of acute unclassified leukaemia.

For further analysis of their lineage affinity the differentiation capacity of five cases of acute unclassified leukaemias were studied in vitro using 5 nM 12-O-tetradecanoyl-phorbol-13-acetate as an inducing agent. After 4 d in vitro a co-expression of both myeloid and early B-lymphoid or myeloid and early T-lymphoid antigens on the same population of cells was found. While ultrastructural analysis of the blasts prior to culture revealed the morphology of undifferentiated blasts without any specific endogenous peroxidase activity, the cultured blasts displayed monoblastic features and myeloperoxidase activity after 4 d in vitro. Since this type of peroxidase is highly specific for the myelomonocytic lineage the data indicate myelomonocytoid differentiation of all five cases studied. The co-expression of lymphoid as well as myeloid antigens and myeloperoxidase by the same blasts after culture could be indicative of bilineage differentiation capacity characterizing the original blasts as bipotential progenitor cells.

Acute Disease↗
PubMed1988

[Intensive combined therapy for high-risk ALL patients].

In the risk-adapted multicenter trial (02/84) for adult ALL the effectiveness of a consolidation therapy consisting of VM26 and Ara-C for high-risk patients was tested. Out of a total of 442 patients in the study, 79.2% achieved a complete remission. For the 182 high-risk patients the median remission duration is 17 months and the probability of being in continuous complete remission (CCR) is 34%. Improved results were found for elderly ALL patients between 35 and 65 years of age, whose median remission duration and CCR rate are 19 months and 40% respectively, compared to 15 months and 26% in the former study 01/81. The consolidation therapy has apparently also benefited patients with the immunological subtype c-ALL, for whom the CCR rate at 3 years is 53% in comparison to the previous value of 34%.

Adolescent↗