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**Prof. Wust** · 08.04.2003, 19:12

RE: Befund

Eigentlich kann ich die Bewertung so nicht nachvollziehen. Die Megakaryozyten (das sind die Stammzellen der Thrombozyten) sind verändert, das ist zu erwarten bei einer Thrombozythämie. Bei einer diskreten Faservermehrung gleich von einer Vorform einer idiopathischen Myelofibrose zu sprechen, scheint etwas spekulativ. Gehen Sie doch weiter von einer essentiellen Thrombozytose aus. Die anderen Blutwerte sind doch normal.
Eine solche Erkrankung sollte normalerweise nicht behandelt werden. Nur wenn Beschwerden auftreten, ist ein (symptomorientierte) Behandlung angebracht. Beobachten ist zunächst die einzige Maßnahme. Im Harrison (Standardlehrbuch der Inneren Medizin, S. 780) steht: „Es gibt kaum eine andere Erkrankung, bei der Ärzte dazu verleitet werden, unangebrachte Maßnahmen einzuleiten, wie bei Thrombozytenzahlen über 1 Mio/µl.“
Sie sollten sich wirklich nicht zu sehr verrückt machen. Ob die Lebenserwartung eingeschränkt oder normal ist, kann man zur Zeit kaum sicher sagen. In solchen Fällen (in denen man sowieso nichts ändern kann) sollte man von einer optimistischen Annahme ausgehen.

**Prof. Wust** · 08.04.2003, 20:34

RE: Befund - Ergänzung

In Ergänzung noch ein paar Arbeiten zu den chronischen myeloproliferativen Erkrankungen. Sie sehen, da ist eine Hochburg in Köln. Vielleicht sollten Sie dort mal nachfragen.

Clinical and morphological criteria for the diagnosis of prefibrotic idiopathic (primary) myelofibrosis.
AU: Thiele,-J; Kvasnicka,-H-M; Zankovich,-R; Diehl,-V
AD: Institute of Pathology, University of Cologne, Joseph-Stelzmannstrasse 9, 50924 Cologne, Germany. [email protected]
SO: Ann-Hematol. 2001 Mar; 80(3): 160-5
AB: A clinicopathological study was performed to define initial-prefibrotic precursor stages of idiopathic (primary) myelofibrosis (IMF) by presenting laboratory and histological bone marrow features. Contrary to the usually accepted diagnostic requirements for IMF, including bone marrow fibrosis and a leukoerythroblastic blood picture, we found that 80 patients did not completely comply with these criteria. In particular, this cohort displayed no increase in the reticulin-collagen fiber content of the bone marrow at onset. Therefore, these cases were occasionally regarded as unclassifiable chronic myeloproliferative disorders (MPDs), or presumptively as essential thrombocythemia (ET). Patients were characterized by a certain set of clinical parameters comprising a borderline to slight leukocytosis and therapy-refractory anemia, minimal to modest splenomegaly, and often an elevated platelet count. Peripheral blood films revealed, only very sparsely, tear drop cells and a few erythroid and myeloid precursors, but no definite leukoerythroblastic reaction. Bone marrow histopathology was consistent with an increase in cellularity and a prominent left-shifted neutrophil granulopoiesis. Erythropoiesis disclosed a slight reduction with small to medium-sized islets. Megakaryopoiesis was the most prominent diagnostic hallmark to distinguish initial-prefibrotic IMF from the allied subtypes of MPDs. This cell lineage was not only characterized by a conspicuous growth and abnormal clustering, but also by a pronounced deviation from nuclear-cytoplasmic differentiation (dysplastic appearance). Cytological anomalies were compatible with a large variety of size and shape, ranging from giant- to atypical micromegakaryocytes with compact and bulky, cloud-like nuclei, due to a coarse lobulation and a frequent occurrence of naked (denuded) nuclei. Follow-up examinations, including sequential trephine biopsies in 22 patients, revealed a transition into myelofibrosis accompanied by laboratory findings in keeping with manifest IMF. In conclusion, morphological and clinical parameters have been validated by this study, which are consistent with a set of diagnostic criteria to recognize initial or prefibrotic precursor stages of IMF.

D34+ stem cells in chronic myeloproliferative disorders.
AU: Thiele,-J; Kvasnicka,-H-M
AD: Institute of Pathology, University of Cologne, Germany. [email protected]
SO: Histol-Histopathol. 2002 Apr; 17(2): 507-21
AB: Contrasting the wealth of information that is available about various biological and therapeutic aspects of human CD34+ stem cells, little data exist concerning their quantity and dynamics as well as their mutual relationships with other hematopoietic constituents in the bone marrow of patients with chronic myeloproliferative disorders. In comparison with a control group frequency of progenitors is significantly increased in chronic myeloid leukemia (CML). Following different therapeutic modalities their quantity reflects therapeutic efficacy (responder and non-responder patients) and therefore exerts a predictive value regarding acceleration and blastic crisis. The significant correlations between fiber content and number of these precursors elucidates the complex interactions between stroma and progenitor cell differentiation and maturation. Following allogeneic bone marrow transplantation there is a rapid recovery of the CD34+ stem cell population in the first month. A higher number of these cells is related with graft size, an earlier independence for platelet transfusion and a more extended regeneration of erythro- and megakaryopoiesis. The slight increase in reticulin fibers in these patients may be associated with the complex and so far ill-defined pathomechanism of homing (adherence to the fibrous matrix). In idiopathic myelofibrosis (IMF) an increased number of CD34+ stem cells is found predominantly in the early (prefibrotic or mild fibrotic) hypercellular stages and probably indicates a higher proliferative activity of the precursor cell pool. According to sequential biopsies most patients with early IMF that later evolved into an overt fibrosclerotic stage usually display a reduction of progenitor cells during the development of myelofibrosis. The unequal distribution of CD34+ stem cells in the bone marrow versus spleen in IMF (advanced fibrosclerotic stage) is in support of the currently discussed hypothesis of splenic filtration and concentration of precursor cells as an essential feature of myeloid metaplasia. Regarding prognosis in CML a higher amount of CD34+ stem cells is significantly associated with an unfavorable survival and thus confirms the assumed implication of an accelerated phase of disease at onset. On the other hand, in polycythemia vera (PV) and IMF a low number of progenitors is probably due to a decreased proliferation rate (reduced hematopoietic turnover index) and therefore reflects a reduction in the regenerative capacity of hematopoiesis. For this reason, a presumptive defect in the recovery of normal and clonally transformed stem cells is speculated to add to the worsening of prognosis by causing the well-known bone marrow insufficiency in terminal stage PV and IMF.

Chronische myeloproliferative Systemerkrankungen. Die neue WHO-Klassifikation.
[Chronic myeloproliferative disorders. The new WHO classification]
AU: Thiele,-J; Kvasnicka,-H-M
AD: Zentrum fur Pathologie der Universitat zu Koln. [email protected]
AB: Except for chronic myelogenous leukemia (CML), chronic myeloproliferative disorders (CMPDs) include as main subtypes polycythemia vera (PV), chronic idiopathic myelofibrosis (IMF), and essential thrombocythemia (ET). A common finding in CMPDs is a clonal evolution associated with a significantly variable course, which may be complicated by thrombocythemia, (secondary) myelofibrosis, and finally acceleration (unstable phase) that merges into blastic crisis. New therapeutic modalities (chemo- and interferon therapy, bone marrow and stem cell transplantation) which were developed in the last decade and the striking differences in survival amongst the different subtypes warrant not only an unequivocal distinction from reactive and allied disorders, but a clear-cut classification as well. For this reason, a synoptical approach is essential including clinical data and, as a major diagnostic tool, a bone marrow biopsy. This concept finds expression in the new WHO classification, which also includes as rare subtypes chronic neutrophilic leukemia, eosinophilic leukemia, chronic hypereosinophilic syndrome, and finally unclassifiable entities. Histopathology of bone marrow biopsies reveals specific findings, in particular concerning megakaryopoiesis, which are characteristic for the different subtypes. These features facilitate the still controversially discussed differentiation of thrombocythemia that is frequently present, as is the case in initial (prefibrotic) IMF from ET. Moreover, in addition to clinical findings,the associated heterogeneity of bone marrow morphology indicates a stepwise evolution of the disease process and thus exerts a significant impact on survival, i.e., in CML regarding erythropoiesis and myelofibrosis and in IMF extent of myeloid metaplasia.

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