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Biomedical subjects

H L Seewann

Publications and source records attributed to H L Seewann.

At least 19 recordsLinked to original sources
PubMed1999

Successful treatment with arsenic trioxide of a patient with ATRA-resistant relapse of acute promyelocytic leukemia.

Arsenic trioxide has recently been introduced as a promising new agent to treat refractory acute promyelocytic leukemia (APL). In the present study, arsenic trioxide was given intravenously for 42 days to a 56-year-old female patient suffering from chemotherapy/ATRA-resistant APL, with 43% APL blasts in the bone marrow and elevated D-dimers. During the first days of arsenic trioxide treatment a rapid decrease in the D-dimers was seen (normal values reached until day 7), together with a slight decrease in peripheral blood leukocytes. This initial coagulation response was followed by a second phase of hematological response (starting on days 15-20) characterized by leukocytosis, occurrence of myeloid progenitor cells in the peripheral blood, and a decrease in bone marrow blasts (<1% on days 28 and 36). Finally, the patient entered complete hematological and cytogenetic remission, although the PML-RAR alpha fusion product was still detectable by PCR. These data confirm the therapeutic value of arsenic trioxide in relapsed/resistant APL.

Antineoplastic Agents↗
PubMed1999

Persisting bone marrow aplasia following interferon-alpha combined with ara-C for chronic myelogenous leukemia.

A 37-year-old man with a newly diagnosed chronic myelogenous leukemia received induction therapy with hydroxyurea and interferon-alpha, and maintenance therapy with low-dose ara-C and interferon-alpha. Subsequent to a rapid hematological remission, a continuously aggravating pancytopenia with bone marrow aplasia developed which persisted after withdrawal of maintenance therapy. Bone marrow examination exhibited aplastic areas and residual hematopoiesis with impaired maturation; cytogenetically, there was a 100% persistence of Philadelphia chromosome-positive metaphases. By allogeneic bone marrow transplantation, a complete reconstitution of hematopoiesis was achieved.

Adult↗
PubMed1998

Efficacy and toxicity of 2-Chlorodeoxyadenosine (Cladribine)--2 h infusion for 5 days--as first-line treatment for advanced low grade non-Hodgkin's lymphoma.

2-Chlorodeoxyadenosine (Cladribine) is a new purine analogue with high activity in pretreated low grade non-Hodgkin's lymphoma (NHL). To evaluate the efficacy of this drug in untreated patients with advanced NHL, we performed a prospective multicentre trial. Cladribine (0.12 mg/kg) was administered intravenously daily for 5 consecutive days in an out-patient setting. The treatment was repeated every 28 days for four cycles. Included were patients with a histological diagnosis of low grade NHL according to the Kiel classification and stage III or IV disease. Stage II patients were included when radiotherapy had failed. 55 patients were entered into the study. 50 patients were evaluable. The remission rate was 44/50 (88%; 95% confidence interval 82-100%), including complete remissions (CR) in 14 (28%) patients. Only 2 patients showed progression while on Cladribine treatment. The estimated overall survival, and time to treatment failure (TTF) were 85% and 51%, respectively, after a median observation time of 92 weeks. 11 (22%) patients showed grade 3 or 4 toxicity according to the WHO grading. Haematological toxicity was responsible for 86% of the overall toxicity and 100% of grade 3 and 4 toxicity. 7 patients (14%) had an infection, two of which were opportunistic. 12 (24%) patients did not experience any toxicity during the treatment. The results of this study clearly demonstrate the safety and considerable activity of this regimen. Cladribine is very effective even at lower doses than have been used so far.

Adult↗
PubMed1996

CEOP-IMVP-Dexa in the treatment of aggressive lymphomas: an Austrian multicenter trial.

PURPOSE: This trial evaluated the efficacy, toxicity, and practicability of a new intensive chemotherapy regimen in a multicenter setting of university and community hospitals. PATIENTS AND METHODS: We tested a hybrid protocol of two non-cross-resistant regimens, cyclophosphamide, epirubicin, vincristine, and prednisolone (CEOP) and ifosfamide, etoposide (VP-16), methotrexate, and dexamethasone (IMVP-Dexa) given every fourth week, three to six times according to response, in patients with untreated intermediate- and high-grade non-Hodgkin's lymphoma. Ten Austrian centers entered 81 patients onto this multicenter trial. Eleven patients were excluded. The median age was 55 years. Twenty-six of 70 patients had stage III or IV disease. The distribution among international risk categories low, intermediate-low, intermediate-high, and high was 20%, 34%, 23%, and 23%, respectively. RESULTS: Of 70 eligible patients, 56 (80%) had a complete remission and seven (10%) a partial remission. After a median observation time of 36 months, the estimated time to relapse and overall survival rates are 67% and 72%, respectively. Age and Karnofsky index were the only independent risk factors for survival. Toxicity was primarily hematologic, with a median granulocyte nadir of 0.56 x 10(9)/L. Sixty-seven percent of patients had infections; 25.7% were severe World Health Organization (WHO) grade III or IV. There were three treatment-related deaths. CONCLUSION: CEOP-IMVP-Dexa chemotherapy is safe and feasible on a groupwide basis even when used in community hospitals. Neutropenic infections are the major complications. A 72% 3-year survival rate in patients with intermediate- and high-grade non-Hodgkin's lymphoma warrants further studies. These data are the basis for a randomized trial to compare cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with CEOP/IMVP-Dexa.

Adolescent↗
PubMed1995

Heavy-chain immunoglobulin gene rearrangement and cytoplasmic immunoglobulin expression in acute monocytic leukemia following primary germ cell tumor.

A case of acute monocytic leukemia with rearrangement of the immunoglobulin heavy-chain gene and strong cytoplasmic immunoglobulin expression in a young patient treated with multi-drug chemotherapy for primary seminomatous germ cell tumor 13 months earlier is reported. The short latency period from the beginning of therapy for primary germ cell tumor and the abrupt onset of leukemia with no identifiable prodrome bear similarities to podophyllotoxin-related leukemias.

Adult↗
PubMed1995

Interferon-alpha for induction and maintenance in multiple myeloma: results of two multicenter randomized trials and summary of other studies.

BACKGROUND: Interferon (IFN) treatment trials in multiple myeloma have yielded discordant results regarding response rates, maintenance duration, and survival times. Further randomized trials and global evaluations of available data are urgently needed for clarification. PATIENTS AND METHODS: 256 patients participated in a randomized trial, 125 on IFN + VMCP, and 131 on VMCP alone. 100 patients were randomized to IFN maintenance (n = 46) or were untreated controls (n = 54). Global evaluations are based on 1,518 patients in induction and 924 in maintenance trials. RESULTS: The induction trial demonstrated a significantly (p < 0.05) lower rate of progressive disease under IFN + VMCP (10.6%) than under VMCP (22.9%), but this benefit was limited to stage I or II patients. Median progression-free survival was longer in the IFN + VMCP arm (23.2 months vs. 15.8 months); median overall survival did not differ significantly (38.9 vs. 30.2 months). The IFN maintenance treatment trial showed significantly superior results in the IFN arm versus controls (median maintenance duration: 17.8 months and 8.2 months (p < 0.01), survival: 50.6 and 34.4 months (p < 0.05), respectively). Previous IFN treatment increased the benefits of IFN maintenance therapy. Adverse effects of IFN during induction were hematologic toxicity, fever, and infections, requiring dose reductions. Toxic effects of IFN maintenance treatment were mild. Global evaluations of randomized trials showed small but significant benefits of combined IFN induction therapy and significantly prolonged maintenance duration and survival under IFN maintenance. CONCLUSIONS: Presently available data support the use of IFN maintenance treatment because it significantly prolongs maintenance duration and survival. IFN added to induction chemotherapy resulted in minor improvements at the expense of increased toxicity, highlighting the need for better induction regimens.

Adult↗
PubMed1993

Chemohormonal and immunohormonal approaches in advanced prostatic carcinoma.

The standard palliative treatment for patients with advanced prostate cancer has for the past 50 years been androgen withdrawal. However, owing to the presence of hormone-insensitive cell clones, the benefits of this approach have now appeared to reach their optimum. It is now generally believed that further major therapeutic advances in the treatment of prostate cancer are unlikely, unless consideration is given to these hormonally independent cells. Two possible alternative strategies which address this problem are chemohormonal and immunohormonal approaches, both of which are discussed in detail in this article.

Androgen Antagonists↗
PubMed1993

[Interferon therapy in essential thrombocythemia].

Interferon-alpha (IFN-alpha) exhibits a clear platelet reductive effect in patients with essential thrombocythemia as well as in other chronic myeloproliferative disorders with thrombocytosis. In a total of 51 patients with chronic myeloproliferative disorders with thrombocytosis we analyzed the effect of IFN-alpha in respect to platelet reduction, remission rates, induction- and maintenance dosage, long term tolerance and side effects. According to our classification CML 6, chronic mega-karyocytic granulocytic myelosis 5, essential thrombocythemia 26 and polycythemia vera 15 patients were treated. Treatment consisted of induction with 3 or 5 MU IFN-alpha daily followed by a maintenance therapy with 3 or 5 MU thrice weekly. Platelet reduction was found in all patients, CR (platelets < 450 G/l) in 78%. Within 2 months of induction therapy, CR in patients treated with 5 MU IFN daily was found in 75% compared to 52% in patients treated with 3 MU IFN daily. Dosage reduction in maintenance periode caused an increase of platelets to more than 450 G/l in 39% of patients. Out of 40 Philadelphia-negative chronic myeloproliferative disorders treated for more than 3 months in 10 patients treatment was disrupted after 5 to 18 months because of the following side effects: nausea, fatigue, vertigo, fever, headache, diarrhea, anorexia, heartburn, hairloss, myalgia, and thrombocytopenia. Due to the mutagenic effect of alkylating cytostatics and Radiophosphorus, IFN-alpha treatment represents a first line strategy for chronic myeloproliferative disorders with thrombocytosis especially in younger patients who are symptomatic and in those who suffered from episodes of bleeding or thrombosis.

Dose-Response Relationship, Drug↗
PubMed1991

Treatment of thrombocytosis in chronic myeloproliferative disorders with interferon alfa-2b.

Thirty-six patients with chronic myeloproliferative disorders (CMPD) with thrombocytosis (essential thrombocythaemia 19 patients, chronic megakaryocytic granulocytic myelosis five, polycythaemia vera six, chronic myelogenous leukaemia six) were treated with interferon alfa-2b to reduce the platelet count. The pre-treatment platelet count was in the range 450-700 x 10(9)/L in eight patients, 700-1000 x 10(9)/L in eight and above 1000 x 10(9)/L in 20. In the induction phase of treatment 22 patients were treated with interferon alfa-2b 3 million units (MU) daily subcutaneously for 2 months or until the platelet count returned to normal, if earlier. Fourteen patients received 5 MU interferon alfa-2b daily in the same way. In the maintenance phase the doses were reduced to 3 MU and 5 MU thrice weekly, respectively. Complete response (CR), defined as a reduction of platelet count to below 450 x 10(9)/L, was achieved in 78% of patients (within 2 months of induction in 64%). The platelet depleting effect was dose dependent: CR in 2 months in 52% on 3 MU interferon alfa-2b versus 75% on 5 MU. Reduction of interferon dose was followed by an increase in platelet count in 39% of patients. The white cell count fell by 50% in Philadelphia-negative CMPD. Side effects were common, though generally mild, but led to withdrawal of treatment in six patients. Three patients suffered cerebrovascular events during treatment and one shortly thereafter.

Adult↗
PubMed1991

Interferon alfa-2b with VMCP compared to VMCP alone for induction and interferon alfa-2b compared to controls for remission maintenance in multiple myeloma: interim results.

The present trial was designed to evaluate whether interferon (IFN) combined with standard induction chemotherapy and/or interferon remission maintenance treatment improve treatment results in patients with multiple myeloma. Up to now 89 patients have received IFN plus vincristine/melphalan/cyclophosphamide/prednisolone (VMCP) as induction therapy, and 86 conventional VMCP. The proportion of patients with progressive disease was significantly lower (P less than 0.005) under IFN + VMCP as compared to the VMCP treatment group. Survival times were significantly longer (P less than 0.02) after IFN + VMCP induction therapy than after VMCP alone. In the second phase of this investigation, 33 progression-free myeloma patients were assigned to receive IFN as maintenance therapy, and 41 patients served as untreated controls. Patients maintained with IFN showed a tendency towards increased progression-free survival. Haematological side effects were observed significantly more often in patients receiving IFN, with more severe haematological toxicity in patients on the combined IFN + VMCP regimen and an increased number of patients with mild haematological toxicity in the group maintained with IFN. Other side effects, such as fever and fatigue, remained within tolerable limits. In conclusion, the preliminary results of this current clinical trial indicate significant advantages of combined IFN + VMCP induction treatment in terms of reduced disease progression and prolonged survival and possible benefits of IFN maintenance therapy in patients with multiple myeloma.

Adult↗
PubMed1991

Non-systemic diffuse lymphangiomatosis of spleen and liver.

We present a 27-year-old woman with non-systemic diffuse lymphangiomatosis of spleen and liver. The tumour consisted of capillary and cavernous lymphatic vessels located in abundant fibrous tissue. The vascular endothelium showed immunoreactivity for factor VIII-related antigen. A basal lamina could be demonstrated immunohistochemically and by electronmicroscopy.

Adult↗
PubMed1988

Interferon-alpha-2 in the treatment of idiopathic myelofibrosis.

We investigated the effect of human recombinant DNA-derived IFN-alpha-2 given in a dose of 1-2 X 10(6) units daily by subcutaneous injection to five patients with advanced idiopathic myelofibrosis (IM). Transfusion dependent anemia and symptomatic splenomegaly were taken as inclusion criteria for this pilot study. Two patients succumbed, one and three months after starting interferon-treatment because of pneumonia and traumatic cranial injury, respectively. While on IFN-treatment no improvement of cytopenia or reduction of splenomegaly was seen in four of the patients. In one patient, however, the requirement for erythrocyte transfusions decreased from 5 to 1.7 monthly upon IFN-treatment. After two, four and six months respectively IFN-treatment had to be stopped in these cases because of progressive thrombocytopenia and/or neutropenia. These observations suggest, that IFN-alpha might be of only marginal value in the treatment of advanced idiopathic myelofibrosis.

Aged↗
PubMed1987

[Recombinant (IFN-alpha 2b) therapy in hairy cell leukemia].

Eighty-five patients with hairy-cell leukemia were treated in a multicentric "open label" study with IFN-alpha 2b and evaluated. Induction therapy was 2 X 10(6) U IFN-alpha 2b/m2, 3 times a week, s.c. The results show this regimen to be highly effective with only a few tolerable and transient side effects consisting mainly of flu-like symptoms. After 6 months of therapy 4% CR, 69% PR, and 16% MR, were noted. In a small group of four patients who had achieved CR or PR, we tested the effect of varying doses for maintenance therapy. Our preliminary results indicate that a relapse caused by interruption of IFN therapy or dose reduction to 3 X 10(6) U given once a week, o.c. could be successfully treated by readministration, or escalating the dosage of IFN. It seems that remission maintenance requires long-term treatment with IFN. In a short-term in vitro test we studied the effect of IFN-alpha 2 on the incorporation of 3H-thymidine and 3H-uridine into hairy cells of five patients. Fort both precursors no appreciable effect was detected. However, after prolonged incubation for 48 h, a significant enhancement of 3H-uridine incorporation was observed, while 3H-thymidine incorporation remained unaffected. Cell marker analysis performed with monoclonal antibodies before and after incubation of hairy cells with IFN-alpha 2 for up to 7 days did not reveal any change of the phenotype of hairy cells.

Clinical Trials as Topic↗
PubMed1986

[Jamshidi biopsy in clinical hematology. Method, indications and results of over 1,000 completed biopsies with special reference to chronic myeloproliferative diseases].

One thousand and five bone marrow biopsies were performed in patients with haematologic or oncologic disorders during a ten year period from 1976 to 1985 according to the method of Jamshidi and Swaim. Indications and method of biopsy are discussed in detail. Major side effects were not observed, however minor accidents (0.2%) as well as problems in yielding biopsy-material (1.6%) are reported. The rate of biopsy-failure, including biopsies with insufficient (crushed) material, was 5%. In our hands the predominant value of the Jamshidi-biopsy for diagnosis of hematologic disorders is given by the following reasons: Bone marrow histology gives a more detailed architectural picture than cytologic smears. Sampling of bone marrow for both methods (cytology and histology) through the same instrument is possible. The procedure is easily performed and gives the patient no more discomfort than a simple sternal puncture. Chronic myeloproliferative disorders (CMPD, 31%), malignant lymphomas (40%) and aplastic (hypoplastic) syndromes (4%) were the most frequent indications for bone marrow biopsy. Clinical and histological findings were compared in 235 patients with CMPD. The histological defined entity of chronic megacaryocytic-granulocytic myelosis could be differentiated easily from chronic granulocytic leukemia (CGL), however it was not always distinguishable from primary thrombocythemia by means of clinical and hematological criteria. Myelofibroses on the basis of CGL were separated from idiopathic or postpolycythemic fibroses by hematological findings. The diagnostic value of bone marrow biopsies was superior to cytology in all CMPD and proved to be an essential diagnostic method in cases with high platelet count. Marrow involvement was found in 59% of 218 previously untreated patients with non Hodgkin's lymphomas and in 9% of 123 patients with Hodgkin's disease. Jamshidi-biopsy proved to be a simple and indispensable procedure in staging of Hodgkin's and non-Hodgkin's lymphomas.

Anemia, Aplastic↗