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  • 1
    Electronic Resource
    Electronic Resource
    Fluorescence in-situ hybridization (FISH) reveals that in chronic myelogenous leukaemia (CML) following interferon-α therapy, normalization of megakaryocyte size is associated with the loss of bcr/abl translocation (1997)
    Oxford, UK : Blackwell Science Ltd
    Histopathology 31 (1997), S. 0 
    Details
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In addition to predominant granulocytic proliferation, bone marrow morphology in Philadelphia chromosome positive (Ph1+) CML is characterized by atypical dwarf or microforms of megakaryocytes. However, following therapy with interferon-α2b (IFN), these micromegakaryocytes occur less frequently. The purpose of this study was to elucidate whether the reappearance of normal megakaryocytes may be associated also with a reduction of the bcr/abl-positive cell clone.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and results:Fluorescence in-situ hybridization (FISH) technique in combination with immunomorphometry (CD61) was performed on trephine biopsies. A total of 311 CD61-positive megakaryocytes, including precursors and atypical microforms, were evaluated in pre-treatment specimens derived from 11 patients with Ph1+ CML. A specific fusion site marking the bcr/abl translocation was found in 87% of megakaryocytes which showed a size of 169 ± 35 μm2. In untreated patients, atypical microforms (size 200 μm2) were observed in 66% of the total megakaryocytic population. Following IFN therapy 369 megakaryocytes could be analysed in sequential examinations and were found to display a significant decrease (63%) in positive fusion signals. In addition there was also a significant enhancement in average size (252 ± 66 μm2) reflecting a reduction in the number of micromegakaryocytes (43%). These findings were particularly conspicuous in three patients with a major to complete cytogenetic remission.〈section xml:id="abs1-3"〉〈title type="main"〉Conclusions:A normalization of megakaryocyte size following IFN therapy in CML is significantly associated with a loss of the bcr/abl translocation site and therefore indicates a (partial) recovery of normal haematopoiesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2559.1997.2480853.x
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  • 2
    Electronic Resource
    Electronic Resource
    Treatment of chronic myelogenous leukemia with interferons alpha and gamma (1990)
    Springer
    Annals of hematology 61 (1990), S. 45-46 
    Details
    ISSN: 1432-0584
    Keywords: Interferon alpha ; Interferon gamma ; Chronic myelogenous leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 23-year-old male patient with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) was treated with both IFN alpha and IFN gamma. Normalization of leukocyte counts was reached after 3 months of treatment. Southern blot analysis failed to detect the neoplastic cell clone after 19 months of therapy. Cytogenetically, complete suppression of Ph positive cells in the patient's bone marrow and blood was observed after 20 months and 25 months, respectively. This response was achieved with doses of IFN alpha and IFN gamma which were considerably lower than the dosage of IFN used in single agent therapy of CML.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01739433
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  • 3
    Electronic Resource
    Electronic Resource
    The impact of interferon versus busulfan therapy on the reticulin stain-measured fibrosis in CML – a comparative morphometric study on sequential trephine biopsies (1995)
    Springer
    Annals of hematology 70 (1995), S. 121-128 
    Details
    ISSN: 1432-0584
    Keywords: Key words CML ; Myelofibrosis ; Dynamics ; Megakaryocytes ; Morphometry ; Interferon ; Busulfan ; Sequential bone marrow biopsies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To evaluate treatment-related changes of the reticulin stain-measured fibrosis in Ph1+-CML, a clinicopathological study was performed on sequential trephine biopsies of the bone marrow following either interferon (IFN) or busulfan (BU) monotherapy. Using the monoclonal antibody CD61 for the identification of megakaryopoiesis and Gomori's silver impregnation method, number of megakaryocytes and density of argyrophilic (reticulin and collagen) fibers were determined by morphometry. We studied specimens from 26 patients with IFN-alpha 2b (including nine patients with additional IFN gamma) therapy and from 23 patients who had received BU. In both groups, repeated bone marrow biopsies (total 125) revealed a significant increase in the fiber content, as well as in the number of megakaryocytes during treatment. To assess the dynamics of myelofibrosis more precisely, computation of differences in the degree of fiber density between the first and last examination was carried out. Regarding the considerable variations in the biopsy intervals, a so-called myelofibrosis progression index (MPI) was calculated. Following this rationale, we were able to demonstrate that, in comparison to the BU-group, speed of progression of bone marrow fibrosis was significantly increased in CML patients treated with IFN. Preliminary statistical analysis indicated a relationship between myelofibrosis on admission, which was always associated with increased growth of megakaryocytes, and the MPI with survival. Even when these parameters were regarded, prognosis was significantly more favorable in the IFN-treated patients. The failure of IFN and BU to inhibit the evolution of myelofibrosis may be related to several conversely acting pathomechanisms. Among others, the inability of both therapeutic agents to reduce the number of megakaryocytes more effectively should be taken into consideration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01682031
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  • 4
    Electronic Resource
    Electronic Resource
    Relation between leukocyte counts and cortisol secretion in CML patients undergoing combined TNF α/IFN α therapy (1992)
    Springer
    Annals of hematology 65 (1992), S. 116-120 
    Details
    ISSN: 1432-0584
    Keywords: TNF α ; IFN α-2b ; Leukocytes ; Cortisol ; ACTH ; CML
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During long-term interferon α-2b (IFN) therapy of Philadelphia chromosome-positive chronic myelogenous leukemia (CML) patients, short-term effects of tumor necrosis factor α (TNF) on peripheral leukocyte counts, as well as cortisol and corticotropin (ACTH) release were studied. TNF (40–160μg/m2) was given as a 2-h infusion on 5 consecutive days every 3 weeks, in addition to s.c. daily IFN injections (4 mio U/m2), to four (two male/two female) patients, who had been treated for more than 8 months with IFN and additionally for 0–7 months with TNF. Leukocyte counts, cortisol, and ACTH were determined at 30-min intervals between 4 p.m. and midnight. Profiles were determined the day before and on day 1 of TNF therapy. Leukocyte numbers decreased 30 min after start of TNF administration and increased 30–60 min later with a rebound until the next TNF application. The increase of leukocyte counts was due mostly to neutrophil granulocytes. ACTH levels increased 30 min, cortisol 60 min, and leukocyte counts 90 min after start of TNF infusion. Metopirone, an inhibitor of cortisol synthesis given to one patient, suppressed the TNF-induced stimulation of cortisol secretion and subsequent increase of leukocyte counts, while ACTH blood levels were enhanced. It was concluded that leukocyte count increases after TNF/IFN administration might be related to TNF-evoked cortisol secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01695809
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  • 5
    Electronic Resource
    Electronic Resource
    The impact of interferon versus busulfan therapy on the reticulin stain-measured fibrosis in CML — A comparative morphometric study on sequential trephine biopsies (1995)
    Springer
    Annals of hematology 70 (1995), S. 121-128 
    Details
    ISSN: 1432-0584
    Keywords: CML ; Myelofibrosis ; Dynamics ; Megakaryocytes ; Morphometry ; Interferon ; Busulfan ; Sequential bone marrow biopsies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate treatment-related changes of the reticulin stain-measured fibrosis in Ph1+-CML, a clinicopathological study was performed on sequential trephine biopsies of the bone marrow following either interferon (IFN) or busulfan (BU) monotherapy. Using the monoclonal antibody CD61 for the identification of megakaryopoiesis and Gomori's silver impregnation method, number of megakaryocytes and density of argyrophilic (reticulin and collagen) fibers were determined by morphometry. We studied specimens from 26 patients with IFN-alpha 2b (including nine patients with additional IFN gamma) therapy and from 23 patients who had received BU. In both groups, repeated bone marrow biopsies (total 125) revealed a significant increase in the fiber content, as well as in the number of megakaryocytes during treatment. To assess the dynamics of myelofibrosis more precisely, computation of differences in the degree of fiber density between the first and last examination was carried out. Regarding the considerable variations in the biopsy intervals, a so-called myelofibrosis progression index (MPI) was calculated. Following this rationale, we were able to demonstrate that, in comparison to the BU-group, speed of progression of bone marrow fibrosis was significantly increased in CML patients treated with IFN. Preliminary statistical analysis indicated a relationship between myelofibrosis on admission, which was always associated with increased growth of megakaryocytes, and the MPI with survival. Even when these parameters were regarded, prognosis was significantly more favorable in the IFN-treated patients. The failure of IFN and BU to inhibit the evolution of myelofibrosis may be related to several conversely acting pathomechanisms. Among others, the inability of both therapeutic agents to reduce the number of megakaryocytes more effectively should be taken into consideration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01682031
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  • 6
    Electronic Resource
    Electronic Resource
    Etoposide in patients with previously untreated non-small-cell lung cancer: a phase I study (1991)
    Springer
    Cancer chemotherapy and pharmacology 28 (1991), S. 59-62 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a phase I study, a range of doses of etoposide (200–370 mg/m2 given i. v. daily on 3 consecutive days) were evaluated for tolerance and response as first-line treatment in 26 patients with non-small-cell lung cancer. The dose-limiting toxicity was myelosuppression, especially leukopenia. At dose levels of 350 and 370 mg/m2 ctoposide per day, leukopenia of WHO grade 4 occurred in two and one of seven patients, respectively. No thrombocytopenia of this degree was observed. Myelosuppression was quickly reversible and noncumulative. Apart from alopecia, nonhematologic organ toxicities above WHO grade 2 were not seen. Toxicity analysis suggests that the recommended dose of single-agent etoposide for phase II studies in untreated patients is 330–370 mg/m2 given i. v. daily for 3 days. At the dose levels tested, 6 (23%) major responses could be induced. All responses were seen at a starting dose of 〉300 mg/m2 per day. The median duration of response was 4 months. The median survival for all patients was 8 months and that for responding patients was 15 months.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00684958
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  • 7
    Electronic Resource
    Electronic Resource
    Metastasierender Leydig-Zell-Tumor des Hodens mit einem Markerenzym (1979)
    Springer
    Journal of cancer research and clinical oncology 94 (1979), S. 325-331 
    Details
    ISSN: 1432-1335
    Keywords: Interstitial cell tumor of testis ; Metastases ; Case report ; Alkaline phosphatase ; Hormonal dysfunction ; Chemotherapy ; Metastasierender Leydig-Zell-Tumor des Hodens ; Fallbericht ; Alkalische Phosphatase ; Hormonelle Dysfunktion ; Chemotherapie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Der metastasierende Leydig-Zell-Tumor des Hodens gehört zu den seltensten menschlichen Neoplasien. Bisher sind 18 Fälle beschrieben worden. Die Mehrzahl dieser Tumoren zeigt hormonelle Aktivitäten. Der von uns beobachtete maligne Leydig-Zell-Tumor weist neben einem ungewöhnlichen Hormonprofil zusätzlich ein Markerenzym — die alkalische Phosphatase — auf. Bei fehlender Radiosensibilität wurde auch mit neueren cytostatischen Substanzen kein Therapieerfolg erreicht. Weniger als 10% aller Leydig-Zell-Tumoren erfüllen die Kriterien der Malignität. Achtzehn Fallbeschreibungen der malignen Form liegen unseres Wissens bisher vor. Wir berichten über einen weiteren Patienten mit histologisch gesichertem Laydig-Zell-Tumor, den klinischen Verlauf, die therapeutischen Erfahrungen mit neueren cytostatischen Substanzen sowie die Besonderheit eines Enzym-Markers.
    Notes: Summary Metastatic interstitial cell tumor of the testis is one of the rarest human neoplasms. This is the nineteenth case to be reported. While most of these tumors are combined with hormonal dysfunction, the present tumor, apart from its uncommon hormonal profile, is remarkable because of its capacity of producing and secreting a marker enzyme, alkaline phosphatase. No response was seen after cytostatic therapy with new antineoplastic agents, such as a combination of adriamycin and cis-diamminedichlorideplatinum (II), and ifosfamide. Considering the lack of radiosensitivity, surgery is the primary modality of treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00419291
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  • 8
    Electronic Resource
    Electronic Resource
    The concept of dose intensification in the treatment of neoplastic disease (1992)
    Springer
    Infection 20 (1992), S. S107 
    Details
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In der vorliegenden Arbeit werden unterschiedliche theoretische und klinische Ansätze, die zu dem Konzept der Dosisintensivierung beigetragen haben, beschrieben. Dieses Konzept beinhaltet, daß die Dosierungen von verabreichten Zytostatika pro Zeiteinheit mitbestimmend für die erfolgreiche Behandlung von Patienten mit malignen Tumorerkrankungen sind. Durch den klinischen Einsatz von rekombinanten hämatopoetischen Wachstumsfaktoren können Nebenwirkungen auf das Knochenmark verringert werden, so daß das Konzept der Dosisintensivierung klinisch besser realisierbar wird. Prospektive randomisierte Studien, bei denen nur die Dosis-Intensität verändert wird, werden vermehrt erforderlich. Es wird sich dann erweisen, ob die Dosisintensivierung zu einer Lebensverlängerung beitragen kann.
    Notes: Summary This paper summarizes different theoretical and clinical approaches contributing to the concept of dose intensification. According to this concept, the amount of antineoplastic drug delivered per time predominantly determines the clinical outcome in patients with neoplastic disease. With the availability of recombinant haemopoietic growth factors haematotoxic side effects might be reduced, making this concept more feasible for clinical use. However, more prospective randomized studies, in which dose-intensity is the only treatment variable, are needed to prove that dose intensification will lead to higher survival rates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01705028
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