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H Gisslinger

Publications and source records attributed to H Gisslinger.

70 records · Page 4Linked to original sources
PubMed1991

[Low dosage long-term treatment with recombinant alpha interferon induces in hairy cell leukemia continuous complete remission].

Long-term treatment with recombinant interferon alpha (IFN) leading to complete remission in a patient with hairy cell leukaemia is presented. Four months after the beginning of treatment with IFN, the parameters of the peripheral blood had normalized. In spite of a continuous dose reduction (to a dose of 1 Mio. U/week) remission could be maintained during the six years of treatment. Two years after the start of treatment with IFN, a metastasizing carcinoma of the prostate was diagnosed, leading to death after four years. With regard to the hairy cell leukaemia, the patient was free of symptoms and the obduction confirmed the complete remission: the histological examination of bone marrow, spleen, liver and lymph nodes showed no more signs of hairy cell leukaemia. This case report shows that long-term treatment with IFN in some cases is effective to induce and to maintain complete remission in hairy cell leukaemia.

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PubMed1990

Erythropoietin treatment of anemia associated with multiple myeloma.

Anemia is a common complication of multiple myeloma. It resolves early in the disease if chemotherapy induces a complete remission, but persists if the disease progresses, causing disabling symptoms and often requiring blood transfusions. We treated 13 patients with myeloma-associated anemia by administering recombinant human erythropoietin three times a week for six months. Eleven patients (85 percent) had steady increases in hemoglobin levels and eventual correction of the anemia. Their symptoms of anemia subsided, and they reported a heightened sense of well-being. No patient had any adverse side effects, particularly episodes of hypertension. Monitoring of the serum M component showed a predominantly stable tumor load without apparent interaction between the underlying disease and the response to erythropoietin therapy. The number of erythroid burst-forming units in the bone marrow and peripheral blood and the level of erythropoiesis in bone marrow smears increased significantly during therapy. Pretreatment serum levels of erythropoietin were higher in the patients who did not respond and in those who required more than two months of treatment before they responded. Serum iron, ferritin, and transferrin concentrations reflected responses to treatment. We conclude that recombinant human erythropoietin is a promising therapeutic tool for treating myeloma-associated anemia.

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PubMed1990

[Defects in the prostaglandin system. IX. Lipoxygenase defect of thrombocytes in a patient with polycythemia vera].

Patients with the myeloproliferative syndrome (MPS) often show morphological and functional platelet abnormalities and an increased incidence of lowered cyclooxygenase- and/or lipoxygenase activity. We present the case history of a 68-year-old male patient with polycythaemia vera in whom an absolute absence of platelet lipoxygenase activity has been detected for the first time in the literature.

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PubMed1990

Impaired conversion of exogenous arachidonic acid by platelets to thromboxane B2 and correction of that deficiency by interferon-alpha.

In the course of an investigation of cyclooxygenase and 12-lipoxygenase activity in platelets of patients with myeloproliferative syndrome receiving treatment with interferon-alpha 2 patients showed unusual results which have not been reported so far. Both patients had thrombocytosis, in one case associated with polycythaemia. In platelets of both patients, a reduced conversion of exogenous 14C arachidonic acid to TXB2 was observed accompanied by a shift in conversion to PGE2 and 12-HETE in one patient and to 12-HETE alone in the other before therapy. These findings were paradoxically associated with evidence of enhanced platelet activation in vivo. Treatment of both patients with interferon-alpha resulted in reversal of the biochemical abnormalities and in clinical remission.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1990

Effect of recombinant interferon-alpha2C on reticuloendothelial function in patients with thrombocytosis.

The aim of the study was to investigate the influence of recombinant interferon-alpha 2C (rIFN-alpha 2C) on the in vivo Fc-dependent phagocytic activity of the reticuloendothelial (RE) system. Fourteen patients with excessive thrombocytosis due to myeloproliferative disorders were studied before and 3 months after initiation of therapy. RE function was determined by measuring the clearance of autologous red blood cells (RBC) labeled with 51Cr and sensitized with anti-D antibody. Eleven of the 14 patients responded to rIFN-alpha 2 treatment (platelets, less than 440 X 10(9)/liter). Rather in contrast to a shortening of platelet half-life and an increase (trendwise) in platelet-bound IgG, rIFN-alpha 2 caused a significant impairment of RE function. Although this finding could in part be accounted for by the treatment-related decrease in splenic volume, statistical analysis revealed a direct influence of rIFN-alpha 2 on RBC clearance (p less than 0.01). Our study results might be explained by an interferon (IFN)-induced, intensified expression of Fc receptors on platelet (and leukocyte) surfaces, possibly enhancing unspecific binding of IgG to their cellular membranes. The subsequent increased platelet uptake may lead to an overloading of the RE system causing impaired reactions to additional stimuli such as IgG-coated RBC.

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PubMed1990

Interferon-alpha-induced morphological changes of megakaryocytes: a histomorphometrical study on bone marrow biopsies in chronic myeloproliferative disorders with excessive thrombocytosis.

Interferon(rIFN)-alpha, a successful therapeutic agent in the control of thrombocytosis, has been shown to suppress human megakaryopoiesis. We investigated bone marrow biopsies from 12 patients with thrombocytosis due to chronic myeloproliferative disorders. Prior to treatment as well as during rIFN-alpha-2c therapy, several morphometric parameters of megakaryopoiesis were evaluated. Megakaryocyte density decreased significantly in all patients, megakaryocyte size decreased in polycythaemia vera, agnogenic myeloid metaplasia, and essential thrombocythaemia, but increased in chronic myeloid leukaemia. The various changes observed during therapy indicate an inhibitory effect of rIFN-alpha-2c on megakaryopoiesis and suggest a selective influence on megakaryocytes at various stages of maturation. Increased numbers of pyknotic (bare) nuclei may reflect a shortening of megakaryocyte life-span. No remarkable changes were found in the fibre content of the bone marrow.

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PubMed1990

[Erythropoietin treatment of tumor-associated anemia in patients with multiple myeloma].

Anemia of malignancy is a complication of neoplastic disease which causes impairing symptoms and often requires blood transfusions. In this clinical trial, we have treated 13 patients suffering from chronic anemia of malignancy and multiple myeloma with recombinant human erythropoietin (rHuEPO) three times a week. Eleven patients responded to the treatment by appropriate increases of their hemoglobin levels and the eventual correction of the anemic state, one non-responding patient had to terminate the treatment early because of transfusion requirements. Under rHuEPO therapy, the evaluated parameters of iron metabolism indicated the enhanced synthesis of hemoglobin. The symptoms of anemia subsided in the responding patients and most of them reported a hightened subjective sense of well-being. No adverse side effects, particularly no episodes of hypertension, were observed in any patient.

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PubMed1990

Long-term alpha-interferon therapy in myelodysplastic syndromes.

The myelodysplastic syndrome (MDS) is characterized by a high probability of leukemic transformation and frequently lethal infections or bleeding episodes. Up to now, no generally accepted form of therapy has been established for MDS. Previous trials with alpha-interferon (IFN-alpha) have shown some beneficial effects. We studied the effects of long-term application of IFN-alpha at higher dosages in patients with "low-risk" MDS. Ten patients were included in the study; eight were treated for a period of 6-36 months. IFN-alpha was administered at a median dosage of 9, 6, 4 mU/week during the first, second, and third year, respectively. Response was determined by the status of peripheral blood and bone marrow. Prolonged exposure to IFN resulted in a response rate of 3/10 (30%). In an additional case, disease progression was retarded during the third year of therapy. The incidences of infections and bleeding events subsided notably. After the withdrawal of IFN, hematological and clinical parameters rapidly deteriorated in some patients. The observed improvement of the patients' susceptibility to infections possibly prolongs their survival and seems to justify further trials on IFN treatment in patients with MDS.

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PubMed1989

Long-term interferon therapy for thrombocytosis in myeloproliferative diseases.

31 patients with thrombocytosis associated with myeloproliferative disorders were included in a prospective trial of long-term interferon therapy. 6 patients (19%) had side-effects which required withdrawal of interferon within one year. 22 patients (71%) achieved and maintained a complete response (platelet count less than 440 x 10(9)/l) for at least twelve months, with reduction or abolition of symptoms associated with thrombocytosis and a significant fall in bone-marrow megakaryocytes. At twelve months, 25 patients were randomly allocated to maintenance or withdrawal of interferon. Thrombocytosis recurred rapidly when treatment was stopped, but a second remission could be achieved by resumption of interferon therapy.

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PubMed1988

[Defects in the prostaglandin system. VIII. A pathologic thrombocyte population in myeloproliferative syndrome, which forms no thromboxane from exogenous arachidonic acid].

In 2 out of 29 patients suffering from the myeloproliferative syndrome a lack of thromboxane conversion by platelets from exogenous arachidonic acid was discovered. In one patient PGE2 (30.9%) and 12-HETE (12-Hydroxyeicosatetraenoic acid) (42.8%) were formed instead, whilst in the other patient 12-HETE (72.9%) was the main metabolic product. In both the patients, serum and plasma TXB2, as well as malondialdehyde, were quite low. It is claimed that this phenomenon is due to the expression of a pathological population of platelets related to the disease.

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PubMed1987

Interferon-alfa corrects thrombocytosis in patients with myeloproliferative disorders.

During previous therapeutic trials with interferon, decreased levels of peripheral platelet counts have been observed. Taking advantage of this effect, we investigated the efficacy of recombinant interferon (rec-IFN) in the treatment of thrombocytosis in myeloproliferative diseases. A total of 15 patients with polycythemia vera, essential thrombocytosis, or chronic myeloid leukemia received rec-IFN-alfa at initial doses of 25-70 x 10(6) units/week; maintenance therapy following week 8 of treatment consisted of 20-35 x 10(6) units/week rec-IFN. Observation periods ranged from 24 to 48 weeks. Significant reductions in the number of platelets were noted in all cases; 12/15 patients achieved platelet counts below 440 x 10(9)/l and maintained those normal values for at least 4 weeks. The number of bone marrow megakaryocytes, which had been increased prior to treatment, diminished during rec-IFN therapy, while the previously shortened platelet half-life further decreased with rec-IFN treatment. During rec-IFN-induced remission, the plasma levels of platelet factors, the activity of natural killer cells, and platelet aggregation showed changes between slight improvement and normal values. Severe side effects were only observed with the highest rec-IFN doses; dosage adjustments were effective in improving or eliminating all treatment-related symptoms. Rec-IFN may prove to be a valuable therapeutic alternative to cytostatic treatment of thrombocytosis in myeloproliferative disorders.

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PubMed1985

Treatment with recombinant interferon-alpha-2C: multiple myeloma and thrombocythaemia in myeloproliferative diseases.

Forty-two patients with multiple myeloma were allocated to two groups to receive either polychemotherapy with vincristine, melphalan, cyclophosphamide and prednisolone, or recombinant interferon-alpha 2C monotherapy. The response rate of 43% in the interferon group was significantly lower than that in the chemotherapy group (89%). Patients with stage I disease showed better response rates than those with stage II or stage III disease. Eleven patients with thrombocythaemia due to polycythaemia vera, chronic myeloid leukaemia or essential thrombocythaemia were treated with recombinant interferon-alpha 2C and complete remissions were achieved in 7 of the 8 evaluable patients. Side-effects were common on interferon therapy, but could be reduced by dose reduction and were reversed by cessation of treatment.

Adult↗
PubMed1985

[Therapy with interferon (recombinant IFN-alpha-2C) in myeloproliferative diseases with severe thrombocytoses].

15 patients with myeloproliferative diseases and thrombocythaemia (7 Polycythaemia vera, 5 essential thrombocythaemia, 3 chronic myelogenous leukaemia) were assigned to a therapy with recombinant interferon (recombinant IFN-alpha-2C) in a prospective, controlled trial. Under therapy all patients showed a significant decrease in thrombocyte values. 51% of the patients revealed thrombocyte values within the normal range after 3 months of IFN therapy. Noted side effects of IFN therapy were dose-dependent and clinically well tolerated by the patients.

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PubMedDate not supplied

Marked and sustained improvement of systemic sclerosis following polychemotherapy for coexistent multiple myeloma.

We present the case of a patient who had systemic sclerosis (SSc) with progressive cutaneous and pulmonary involvement and a coexisting monoclonal gammopathy which gradually progressed to overt multiple myeloma. Strikingly, successful VMCP (vincristine, melphalan, cyclophosphamide and prednisolone) polychemotherapy for myeloma was accompanied by a marked and sustained improvement of SSc that has persisted for 2 years after chemotherapy. Most noticeable was a substantial skin softening in our patient, with a > 50% reduction in the skin thickness score following VMCP treatment. Our case suggests that polychemotherapy may represent a promising treatment option in patients with SSc who are refractory to available treatments.

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PubMedDate not supplied

Efficacy of cyclosporin A in systemic sclerosis.

In this open pilot study, the potential therapeutic efficacy of Cyclosporin A (CsA) in systemic sclerosis (scleroderma) was investigated. Eight patients with severe scleroderma (skin manifestation and at least three organ manifestations such as pulmonary, intestinal, cardiac, renal, and severe hypertension) were included in the study. CsA administration was started at a dose of 5 mg per kg body weight per day and then, to obtain whole blood levels of 300-500 ng/ml, adjusted to a mean dosage of 4.3 mg/kg/day. Therapeutic effects were evaluated by monitoring the measures of cutaneous, pulmonary, cardiac, gastrointestinal, and renal involvement as well as laboratory parameters. After 6 to 12 months of CsA-administration, cutaneous abnormalities improved in seven, arterial oxygen tension slightly increased in four, pulmonary hypertension decreased in five, and smooth muscle esophageal contraction amplitudes improved in three patients. However, the disease progressed in one patient. No serious side effects were observed, and occurring renal side effects were mild. Taken together, these observations indicate that CsA administration may be effective mainly in the skin involvement, but also in some organ manifestations of scleroderma. The results of this pilot investigation therefore indicate that a controlled study of the efficacy of CsA in scleroderma is needed and ought to be performed.

Adult↗