10 results on '"Zankovich, R."'
Search Results
2. Polycythemia vera megakaryocytes but not megakaryocytes from normal controls and patients with smokers polyglobuly spontaneously express IL-6 and IL-6R and secrete IL-6
- Author
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Wickenhauser, C, Thiele, J, Lorenzen, J, Schmitz, B, Frimpong, S, Schramm, K, Neumann, I, Zankovich, R, and Fischer, R
- Published
- 1999
- Full Text
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3. ASSESSMENT OF IMATINIB 400MG AS FIRST LINE TREATMENT OF CHRONIC MYELOID LEUKEMIA: 10-YEAR SURVIVAL RESULTS OF THE RANDOMIZED CML STUDY IV
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Hehlmann, R., Lauseker, M., Saussele, S., Pfirrmann, M., Krause, S., Kolb, H-J, Neubauer, A., Hossfeld, D. K., Nerl, C., Gratwohl, A., Baerlocher, G. M., Heim, D., Fabarius, A., Haferlach, C., Schlegelberger, B., Mueller, M. C., Jeromin, S., Proetel, U., Kohlbrenner, K., Burchert, A., Voskanyan, A., Rinaldetti, S., Goebeler, M., Dengler, J., Ho, A., Falge, C., Kanz, L., Kneba, M., Stegelmann, F., Pfreundschuh, M., Waller, C. F., Spiekermann, K., Fuchs, R., Scheid, C., Haenel, M., Koehne, C-H, Bruemmendorf, H., Lindemann, H-W, Berdel, W. E., Staib, P., Balleisen, L., Brossart, P., Schenk, M., Zankovich, R., Geer, T., Hertenstein, B., Bildat, S., Hochhaus, A., Hasford, J., Hehlmann, R., Lauseker, M., Saussele, S., Pfirrmann, M., Krause, S., Kolb, H-J, Neubauer, A., Hossfeld, D. K., Nerl, C., Gratwohl, A., Baerlocher, G. M., Heim, D., Fabarius, A., Haferlach, C., Schlegelberger, B., Mueller, M. C., Jeromin, S., Proetel, U., Kohlbrenner, K., Burchert, A., Voskanyan, A., Rinaldetti, S., Goebeler, M., Dengler, J., Ho, A., Falge, C., Kanz, L., Kneba, M., Stegelmann, F., Pfreundschuh, M., Waller, C. F., Spiekermann, K., Fuchs, R., Scheid, C., Haenel, M., Koehne, C-H, Bruemmendorf, H., Lindemann, H-W, Berdel, W. E., Staib, P., Balleisen, L., Brossart, P., Schenk, M., Zankovich, R., Geer, T., Hertenstein, B., Bildat, S., Hochhaus, A., and Hasford, J.
- Published
- 2017
4. Bone marrow features improve prognostic efficiency in multivariate risk classification of chronic-phase Ph¹⁺ chronic myelogenous leukemia : A multicenter trial
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Kvasnicka, H.M., Thiele, J., Schmitt-Graeff, A., Diehl, V., Zankovich, R., Niederle, Norbert, Leder, Lutz-Dietrich, and Schaefer, H.E.
- Subjects
Medizin - Published
- 2001
5. Randomized comparison of busulfan and hydroxyurea in chronic myelogenous leukemia: prolongation of survival by hydroxyurea. The German CML Study Group
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Hehlmann, R, Heimpel, H, Hasford, J, Kolb, HJ, Pralle, H, Hossfeld, DK, Queiβer, W, Löffler, H, Heinze, B, Georgii, A, Wussow, P.v., Bartram, C., Grieβhammer, M., Bergmann, L., Essers, U., Falge, C., Hochhaus, A., Queiβer, U., Sick, C., Meyer, P., Schmitz, N., Verpoort, K., Eimermacher, H., Walther, F., Westerhausen, M., Kleeberg, U.R., Heilein, A., Käbisch, A., Barz, C., Zimmermann, R., Meuret, G., Tichelli, A., Berdel, W.E., Kanz, L., Anger, B., Tigges, F.J., Schmid, L., Brockhaus, W., Zankovich, R., Schlafer, U., Weiβenfels, I., Mainzer, K., Tobler, A., Perker, M., Hohnloser, J., Messener, D., Thiele, J., Buhr, T., and Ansah, H.
- Abstract
In a randomized multicenter study the influence of hydroxyurea versus busulfan on the duration of the chronic phase and on survival of chronic myelogenous leukemia (CML) was determined. In addition cross resistance and adverse reactions of the drugs were analyzed. From July 1983 to January 1991, 441 CML patients were randomized to receive hydroxyurea or busulfan. Of these, 90.7% were Philadelphia positive; 25.7% were low, 38.2% intermediate, and 36.2% high risk patients according to Sokal's score. The median survival of the busulfan treated Philadelphia-positive patients is 45.4 months and of the hydroxyurea group 58.2 months (P = .008). The survival advantage for the hydroxyurea treated patients is recognized in all risk groups. Sixty four patients reached therapy resistance before blast crisis and were crossed over to the alternative drug. The 23 patients with primary hydroxyurea had a median survival of 5.6 years, the 41 patients with primary busulfan therapy a median survival of 2.7 years (P = .02). Adverse reactions were less frequent with hydroxyurea with no severe adverse effects (lung fibrosis, long lasting bone marrow aplasia). The analysis of white blood cell counts in the course of treatment showed lower counts in the hydroxyurea patients. We conclude that hydroxyurea is superior to busulfan in therapy of CML in chronic phase and should be used as first line therapy. Busulfan may have a role as secondary therapy after hydroxyurea resistance or intolerance.
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- 1993
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6. Randomized Comparison of Interferon-α With Busulfan and Hydroxyurea in Chronic Myelogenous Leukemia
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Hehlmann, R., Heimpel, H., Hasford, J., Kolb, H.J., Pralle, H., Hossfeld, D.K., Queißer, W., Löffler, H., Hochhaus, A., Heinze, B., Georgii, A., Bartram, CR., Grießhammer, M., Bergmann, L., Essers, U., Falge, C., Queißer, U., Meyer, P., Schmitz, N., Eimermacher, H., Walther, F., Fett, W., Kleeberg, U.R., Käbisch, A., Nerl, C., Zimmermann, R., Meuret, G., Tichelli, A., Kanz, L., Tigges, F.-J., Schmid, L., Brockhaus, W., Tobler, A., Reiter, A., Perker, M., Emmerich, B., Verpoort, K., Zankovich, R., Wussow, P.v., Prümmer, O., Thiele, J., Buhr, T., Carbonell, F., and Ansari, H.
- Published
- 1994
- Full Text
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7. Follow-up examinations including sequential bone marrow biopsies in essential thrombocythemia (ET): a retrospective clinicopathological study of 120 patients.
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Thiele J, Kvasnicka HM, Schmitt-Graeff A, Zankovich R, and Diehl V
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- Adult, Aged, Aged, 80 and over, Biopsy, Classification methods, Cohort Studies, Disease Progression, Female, Follow-Up Studies, Hematopoiesis physiology, Humans, Male, Middle Aged, Primary Myelofibrosis etiology, Retrospective Studies, Survival Rate, Thrombocythemia, Essential classification, Thrombocythemia, Essential complications, World Health Organization, Bone Marrow Cells pathology, Thrombocythemia, Essential pathology
- Abstract
Diagnosis of essential thrombocythemia (ET) has been usually established by regarding the criteria of the Polycythemia Vera Study Group. Accordingly, a retrospective clinicopathological study was performed on 120 patients with a follow-up ranging between 5 and 13 years and repeated bone marrow trephine examinations. Following the new WHO classification, at presentation patients revealed three distinctive patterns of bone marrow (BM) features: (true) ET in 43 patients, prefibrotic idiopathic myelofibrosis (IMF) in 50 patients, and early IMF in 27 patients. Heterogeneity of morphological features was associated with correspondingly expressed laboratory data. Contrasting initial and early IMF, patients with true ET displayed an about 80% probability to lack splenomegaly, anemia, and increase in the LDH and LAP values and also failed to show any myeloblasts or erythroblasts on the peripheral blood films. Follow-up examinations including sequential BM biopsies (mean interval 39 +/- 31 months) disclosed that of the 43 patients with true ET only one developed an increase in reticulin. On the other hand, 65 of 77 patients with prefibrotic and early IMF evolved into overt myelofibrosis-osteosclerosis. Moreover, survival analysis demonstrated significant differences in our patients. A neglectable proportion of life loss according to a sex- and age-matched general population was found in true ET (less than 11%) opposed to IMF without or mild fibrosis (range 21% to 32%)., (Copyright 2002 Wiley-Liss, Inc.)
- Published
- 2002
- Full Text
- View/download PDF
8. The value of bone marrow histology in differentiating between early stage Polycythemia vera and secondary (reactive) Polycythemias.
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Thiele J, Kvasnicka HM, Zankovich R, and Diehl V
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- Adult, Aged, Diagnosis, Differential, Female, Histocytochemistry, Humans, Male, Middle Aged, Polycythemia etiology, Polycythemia pathology, Polycythemia Vera pathology, Retrospective Studies, Bone Marrow pathology, Polycythemia diagnosis, Polycythemia Vera diagnosis
- Abstract
Background and Objectives: The diagnostic criteria of the Polycythemia Vera Study Group (PVSG), although generally acknowledged as the gold standard for establishing a diagnosis of polycythemia vera (PV), do not consider bone marrow features. It may, therefore, be speculated that initial-early stages of PV are overlooked. In this retrospective study we tried to investigate whether bone marrow morphology of patients with an only borderline to slight increase in hemoglobin/hematocrit not conforming with the postulates of the PVSG enabled a clear-cut differentiation between PV and secondary (reactive) polycythemias (SP)., Design and Methods: From a series of 348 patients with a borderline to pronounced erythrocytosis and representative pre-treatment bone marrow trephine biopsies a cohort of 86 cases was selected showing only a borderline increase in hemoglobin (males < 18.5 g/dL, females < 16.5 g/dL). Biopsies and clinical records were evaluated independently and following histologic and clinical work-up a straightforward consensus was reached. The diagnostic impact of histologic findings was tested by means of discriminate analysis of 20 standardized morphologic features based on histochemical and immunohistochemical staining techniques., Results: Bone marrow histopathology in 47 patients diagnosed as having SP was characterized by a minimal to slight increase in cellularity with predominance of the erythroid lineage. Neutrophil granulocytopoiesis was prominent and left-shifted and small to medium-sized megakaryocytes without maturation defects were scattered throughout the bone marrow. There was an increased number of eosinophils, marked perivascular plasmacytosis, histiocytic reticular cells with accumulated cell debris and many iron-laden macrophages. Contrasting this appearance in SP our 39 patients with initial-early stage PV revealed a hypercellular bone marrow with trilineage proliferation (pan-myelosis) showing confluent sheets of erythropoiesis and loose clusters of megakaryocytes. Megakaryocytopoiesis was characterized by a pleomorphous appearance, i.e. giant cells were lying adjacent to small ones, but lacked an obvious cytologic abnormality. There was usually no prominent inflammatory reaction of the interstitial compartment. In ten patients lymphoid nodules were found, but no conspicuous iron deposits and in six patients a borderline to minimal increase in reticulin fibers was present. Following stepwise discriminate analysis of histologic features a set of parameters emerged including increase in megakaryocyte size, perivascular plasma cells, overall bone marrow cellularity and cellular debris. This pattern exerted a significant impact on separation (Wilks' lambda statistics = 0.110, p < 0.0001) of early stage PV from SP. Most patients with SP had an underlying bronchopulmonary condition, frequently associated with heavy smoking or rarely renal pathology. In addition to the histopathologic features, splenomegaly, thrombocyte count, LDH, LAP and erythropoietin levels proved to be different in the two groups of patients., Interpretation and Conclusions: Initial-early PV is characterized by a specific pattern of bone marrow histopathology. Clinical features of distinctive impact include splenomegaly, thrombocyte count, LDH, LAP and in particular erythropoietin level. Taking these clinical and histologic findings into consideration, reactive-secondary causes of polycythemia (SP) are clearly distinguishable from autonomous ones (PV).
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- 2001
9. Relevance of bone marrow features in the differential diagnosis between essential thrombocythemia and early stage idiopathic myelofibrosis.
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Thiele J, Kvasnicka HM, Zankovich R, and Diehl V
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- Adult, Aged, Aged, 80 and over, Cohort Studies, Diagnosis, Differential, Erythropoiesis, Female, Follow-Up Studies, Humans, Male, Megakaryocytes cytology, Middle Aged, Primary Myelofibrosis etiology, Primary Myelofibrosis pathology, Retrospective Studies, Survival Rate, Thrombocythemia, Essential pathology, Bone Marrow pathology, Primary Myelofibrosis diagnosis, Thrombocythemia, Essential diagnosis
- Abstract
Background and Objectives: Diagnosis of essential thrombocythemia (ET) remains a challenging problem and has been predominantly established by exclusion of other thrombocythemic disorders. In this context the updated diagnostic criteria of the Polycythemia Vera Study Group (PVSG) are generally accepted, although histopathologic features of the bone marrow were only marginally considered., Design and Methods: A retrospective evaluation was performed of 168 patients presenting with ET in accordance with the criteria of the PVSG. Analysis was focused on the discriminating impact of bone marrow morphology., Results: Histopathology revealed that our cohort of patients could be divided into three distinct groups (true ET, questionable ET and false ET). These groups were characterized by certain diagnostic constellations of clinical data on admission. True ET was found in 53 patients presenting with no or a borderline splenomegaly and no relevant anemia or leuko-erythroblastic blood picture. The other patients showed clinical signs and symptoms which were more compatible with initial-prefibrotic (52 patients) or early (68 patients) idiopathic-primary myelofibrosis (IMF) with severe thrombocythemia. In true ET no significant hypercellularity of the bone marrow including myeloid precursors or an increase in reticulin fibers was detectable. Most prominent were changes of megakaryopoiesis which revealed large to giant-sized cells lacking a definite maturation defect. Their appearance in true ET contrasted with the clusters of abnormally differentiated, often bizarre elements of this lineage in patients with initial and early IMF (questionable or false ET). Calculation of survival disclosed a relevant disparity with a non-significant loss in life expectancy of 10.9% in true ET compared to 29.6% in questionable and 51.3% in false ET. Follow-up studies and repeated bone marrow biopsies revealed no transition into myelofibrosis in true ET, whereas this did occur in 22 of 27 patients with questionable and false ET. In the latter cohort bone marrow changes were accompanied by increasing anemia, splenomegaly, tear-drop poikilocytosis and reduction of the platelet count consistent with IMF., Interpretation and Conclusions: A detailed evaluation of bone marrow features, in particular megakaryopoiesis is recommended to establish positive criteria for the diagnosis of ET and thus to accomplish a significant improvement of the PVSG postulates. In this context ongoing clinical trials on ET must regard pretreatment bone marrow biopsies as a major clue to diagnosis.
- Published
- 2000
10. Erythropoiesis in primary (idiopathic) osteomyelofibrosis: quantification, PCNA-reactivity, and prognostic impact.
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Thiele J, Windecker R, Kvasnicka HM, Titius BR, Zankovich R, and Fischer R
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- Aged, Biopsy, Bone Diseases pathology, Bone Marrow pathology, Bone Marrow Diseases pathology, Female, Fibrosis, Humans, Male, Prognosis, Proliferating Cell Nuclear Antigen, Bone Diseases blood, Bone Diseases immunology, Bone Marrow Diseases blood, Bone Marrow Diseases immunology, Erythropoiesis, Nuclear Proteins analysis
- Abstract
In 64 patients with primary (idiopathic) osteomyelofibrosis (OMF), a morphometric analysis has been performed on bone marrow trephine biopsies following sequential double-immunostaining with monoclonal antibodies against proliferating cell nuclear antigen (PCNA) and erythroid precursor cells (glycophorin C). The purpose of this study was to quantify erythropoiesis and its PCNA-staining capacity and, further, to determine the impact of these parameters for the development of anemia and for prognosis. In comparison with a control group (15 patients), a significant reduction in the number of erythro-normoblasts could be demonstrated, associated with an increase in PCNA-labelling. Moreover, significant correlations between the amount of nucleated erythroid marrow cells and degree of anemia (hemoglobin level, hematocrit, erythrocyte count) and survival could be calculated. Adverse relationships were assessed between number of erythroid cells, thrombocyte count, and spleen size, and also argyrophilic (reticulin/collagen) fiber density. These interactions were thought to reflect the biological behaviour of the disease process, i.e., the progression or extent of myeloid metaplasia. Our findings support ferrokinetic studies suggesting erythroid hypoplasia as one of the major causes of anemia in OMF. The remarkable high PCNA-labelling index of the macrocytic-megaloblastoid appearing erythropoiesis is probably caused by an overexpression of this marker protein. A comparative evaluation of Ki-67 antigen immunostaining in splenic tissue (myeloid metaplasia) and of the PCNA-labelling in pernicious anemia lend support to the assumption of an undue prolongation of the S-phase generated by secondary folate (hematinic) deficiency.
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- 1994
- Full Text
- View/download PDF
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