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  • 1
    Electronic Resource
    Electronic Resource
    Proliferating cell nuclear antigen expression by erythroid precursors in normal bone marrow, in reactive lesions and in polycythaemia rubra vera (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Histopathology 22 (1993), S. 0 
    Details
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Using a sequential double-imunostaining technique, a morphometric analysis was performed on routinely processed bone marrow trephines from 20 patients with secondary (reactive) polycythaemia and 28 patients with polycythaemia rubra vera to determine the proliferation capacity of erythropoiesis. Monoclonal antibodies PC10—anti-proliferating cell nuclear antigen (PCNA)—and Ret40f—anti-glycophorin C—were employed. For comparison with the PCNA-labelling index, in a pilot study, Ki-67 was additionally used on frozen-section material. In comparison with normal bone marrow (15 patients) morphometric and statistical evaluation revealed a numerical increase in erythroid precursors (pro-, erythro- and normoblasts) in secondary polycythaemia and to a pronounced degree in polycythaemia rubra vera. In comparison with secondary polycythaemia and the control group, in polycythaemia rubra vera there was a significant enhancement of proliferation according to PCNA-staining reactivity in all haematopoietic cell elements and particularly in the erythroid series. Evaluation of PCNA v. Ki-67 immunostaining disclosed only a slight difference, which could be mainly attributed to various modalities of antigen expression during the cell cycle. Our findings are in keeping with in vitro studies on cultured erythroid progenitor cells and, in problematic cases, may present a valuable aid in differentiation between reactive lesions and polycythaemia rubra vera.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2559.1993.tb00156.x
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  • 2
    Electronic Resource
    Electronic Resource
    Histomorphometry of bone marrow biopsies in chronic myeloproliferative disorders with associated thrombocytosis - features of significance for the diagnosis of primary (essential) thrombocythaemia (1988)
    Springer
    Virchows Archiv 413 (1988), S. 407-417 
    Details
    ISSN: 1432-2307
    Keywords: Chronic myeloproliferative disorders ; Thrombocytosis ; Primary Thrombocythaemia ; Granulo ; Erythrocytopoiesis ; Reticulin Fibers ; Circular Deviation ; Histomorphometry ; Bone marrow biopsies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A histomorphometric analysis was performed on trephine biopsies of the bone marrow in 55 patients with chronic myeloproliferative disorders (CMPDs) and marked thrombocytosis (platelet count exceeding 600 × 109/l). This study aimed at discriminating primary (essential) thrombocythaemia (PTH) from the various other subtypes of CMPDs presenting with thrombocytosis. Following the diagnostic requirements postulated by the Polycythemia-vera-Study-Group for PTH and polycythaemia vera rubra (P.vera) and the generally accepted criteria for the establishment of chronic myeloid leukaemia (CML) and agnogenic myeloid metaplasia (AMM), our cohort of 55 patients was divided into the following subgroups: CML (16 cases), P.vera (11 cases), AMM (13 cases) and finally PTH (15 cases). Histomorphometric measurements revealed that PTH was distinguishable from the other subtypes of CMPDs with respect to several histological variables: patients with PTH had a normal amount of neutrophilic granulo- and erythrocytopoiesis as well as a non-increased content of reticulin (argyrophilic) fibers in contrast to the findings in CML, P.vera and of course AMM. Moreover, sizes of megakaryocytes and their nuclei were significantly greater in PTH and internalization of haematopoietic cells (emperipolesis) was more frequently encountered in comparison with the other subtypes of CMPDs. Deviation of the circular perimeter of megakaryocyte shape was most prominently expressed in CML and AMM, and consequently generated an increased number of a-nuclear cytoplasmic fragments. In contrast to this feature aberration of the nuclei from a circular outline occurred in a less pronounced way in CML, but was excessive in P.vera, AMM and PTH. Our morphometric evaluation demonstrates that certain histological features may serve as a valuable aid in discriminating PTH from the other occasionally thrombocythaemic subtypes of CMPDs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00716989
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  • 3
    Electronic Resource
    Electronic Resource
    Randomized study on the treatment of chronic myeloid leukemia (CML) in chronic phase with busulfan versus hydroxyurea versus interferon-alpha (1988)
    Springer
    Annals of hematology 56 (1988), S. 87-91 
    Details
    ISSN: 1432-0584
    Keywords: CML ; Busulfan ; Hydroxyurea ; Interferon-alpha ; Duration of chronic phase ; Prospective study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary For palliative therapy during the chronic phase of CML busulfan has proved to be the drug of choice. During the past years hydroxyurea and also interferon-alpha have gained increasing significance since they might prolong the duration of the chronic phase. In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon-alpha instead of busulfan prolongs the duration of the chronic phase of Philadelphia positive CML. Additional goals are the examination of whether the types of disease evolution and the terminal phases differ between the treatment groups, and the prospective recognition of prognostic criteria for the duration of the chronic phase of CML. By December 31, 1987, 326 CML-patients had been randomized, 150 for busulfan, 150 for hydroxyurea and 26 for interferon-alpha. The average age is 50 years. 59 patients reached the end of the chronic phase, 55 died. The mean observation time of all patients is 1.34 years. At present no significant difference in survival is recognizable between the busulfan and hydroxyurea groups. Fewer adverse effects have been observed in the hydroxyurea group. Philadelphia chromosome negative patients show a higher average age and tend to have lower white blood cell and platelet counts. The number of patients having received interferon-alpha is still too small to allow evaluation. This report intends to document organization and progress of this study which to our knowledge is, at present, the largest ongoing prospective multicenter study on the therapy of CML.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00633471
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  • 4
    Electronic Resource
    Electronic Resource
    Histological features of prognostic significance in CML — an immunohistochemical and morphometric study (multivariate regression analysis) on trephine biopsies of the bone marrow (1993)
    Springer
    Annals of hematology 66 (1993), S. 291-302 
    Details
    ISSN: 1432-0584
    Keywords: CML ; Morphometry ; Immunostaining (CD61, PG-M1) ; Prognostic variables ; Cox models ; Life expectancy ; ROC analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To evaluate the prognostic significance of clinical as well as histological disease features at the time of diagnosis, an immunohistochemical and morphometric study was performed on bone marrow trephine biopsies in 130 patients with Ph1+-CML. For identification of all cell elements of the megakaryocytopoiesis we used the monoclonal antibody CD61 (Y2/51) and for the macrophages, the recently characterized antibody PG-M1. Density of argyrophilic fibers was determined per fat cell-free marrow area. Based on a multivariate analysis-derived risk model, the reproducibility of the prognostic score described by Sokal and co-workers was tested, particularly with regard to histological variables. Additionally, we calculated the disease-specific loss in life expectancy. Our prognostic model (Cox model) consisted of the variables: age, spleen size, peripheral erythro-normoblasts, pseudo-Gaucher cells, and fiber density. To assess the validity of this new CML score, a receiver-operating curve (ROC) of sensitivity and specificity was constructed. The improved prognostic efficiency of this newly developed risk model in predicting death within 3 years after diagnosis of CML was demonstrated in comparison with generally accepted staging systems. Immunohistochemistry revealed that not the total number of macrophages, but only the subfraction of pseudo-Gaucher cells exerted a significant impact on survival. Furthermore, it was feasible to calculate the number of atypical micromegakaryocytes and pro-and megakaryoblasts. This abnormal and immature cell population showed a significant correlation with fiber density and prognosis. Finally, the practical value of the Hannover classification was tested. This histological classification enabled a discrimination between two groups with different survival patterns, i.e., granulocyte and/or megakaryocyte-rich subtypes versus subtypes with increase in reticulin and collagen fibers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01695971
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  • 5
    Electronic Resource
    Electronic Resource
    Prognostic impact of apoptosis and proliferation in idiopathic (primary) myelofibrosis (1999)
    Springer
    Annals of hematology 78 (1999), S. 65-72 
    Details
    ISSN: 1432-0584
    Keywords: Key words Idiopathic myelofibrosis ; PCNA labeling ; Apoptosis ; Dynamic disease features ; Prognosis ; Proportion of life loss ; Bone marrow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A retrospective study of 120 patients with the clinically and histologically established diagnosis of idiopathic (primary) myelofibrosis (IMF) was performed to determine prognostic factors of predictive value, including parameters characterizing the dynamics of hematopoietic cell kinetics. In contrast to previous studies, our cohort comprised the full spectrum of the disease, from initial prefibrotic to advanced osteosclerotic stages. The in situ end-labeling (ISEL) technique was used to demonstrate apoptosis, in order to determine dynamic parameters of predictive value. Cell proliferation was evaluated by employing the monoclonal antibody PC10 directed against proliferating cell nuclear antigen (PCNA). Proliferative activity (PCNA index) and frequency of apoptosis showed significant differences between early and advanced fibrosclerotic stages of disease. Decrease in proliferation indicated a significantly shorter survival, whereas a higher frequency of apoptotic cells was associated with a better prognosis. It may be speculated that a normal or enhanced proliferation rate expressed by PCNA positivity (late G1- and S-phase of the cell cycle) that is accompanied by a higher incidence of apoptosis reflects the regenerative (turnover) capacity of hematopoiesis. This may apply especially to early hypercellular stages without relevant myelofibrosis. In consideration of a recently published multivariate risk model, a simplified synthesis score for stratification of a patient's prognosis was constructed. Age, degree of anemia, leukocytes, and platelet count were regarded as the most important parameters. A substantial improvement of prognostic efficiency was further achieved by including PCNA index and frequency of apoptosis. Our results are in keeping with the assumption that generalization, indicated by myeloid metaplasia, has a prodigious impact on prognosis in IMF. Furthermore, in this context dynamic features such as proliferative activity and frequency of apoptosis exert an additional predictive value.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050474
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  • 6
    Electronic Resource
    Electronic Resource
    Differentiation of plasma cell infiltrates in the bone marrow (1988)
    Springer
    Virchows Archiv 412 (1988), S. 553-562 
    Details
    ISSN: 1432-2307
    Keywords: Plasma cell infiltrates ; Bone marrow biopsies ; Malignant myeloma ; Reactive plasmacytosis ; Benign monoclonal gammopathy ; Immunohistochemistry ; Osteoclastic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 80 patients immunohistochemical, morphometrical and clinical studies were performed on routinely referred trephine biopsies of the bone marrow showing an abnormal increase in plasma cells. From the approximately determined density of plasma cell infiltrates two main groups were distinguished, the first with an involvement exceeding 20% and the second with less than 10% of the total marrow area involved. The first group (n=30; 324±130 plasma cells per square millimeter bone marrow) consisted of patients with frank malignant myeloma (MM) by clinical and histomorphological diagnosis. The second group (n=50; 132±54 plasma cells per square millimeter bone marrow) with plasmacytic differentiation of infiltrates, had to be further divided into one component with evidence for initial or residual MM following chemotherapy (n=27), another with obviously monoclonal gammopathy of undetermined significance - benign monoclonal gammopathy (BMG,n=6), and a final set of cases with a reactive plasmacytosis mostly associated with an inflammatory condition (n=17). There was an excellent agreement between the intracellular immunoglobulin staining as defined by the immunoperoxidase technique and the serum or urinary M-component detected by immunoelectrophoresis. In MM significant correlations were found between osteoclastic activity (number of osteoclasts specifically stained by acid phosphatase) per trabecular bone area, presence of lytic bone defects and the density of plasma cell infiltrates in the marrow. This latter feature corresponded well with the titer of secreted serum M-components measured by quantitative immunoelectrophoresis. Using morphological data alone, BMG cases could not be discriminated with any certainty from initial or residual plasmacytic MM. They consequently need a prolonged clinical follow up to clarify the nature of the lesions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00844291
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