BM fibrosis identifies a distinct subgroup of MDS with multilineage dysplasia, high transfusion requirement, and poor prognosis and represents an independent prognostic factor that may be useful in clinical decision making. Furthermore, the presence of CD34+ cell clusters is an independent risk factor for progression to acute leukemia.
We performed 221 marrow trephine biopsies in 139 patients with Ph1-positive (Ph1+) chronic granulocytic leukaemia (CGL) in order to assess the incidence, degree and prognostic significance of marrow fibrosis (MF) at various stages of the disease. We also attempted to elucidate the relationship between development of MF and the various clinical and haematological features of CGL. A significant correlation was found between the amount of fibrosis (graded from 0 to 3) and the stage of CGL, indicating that major fibrotic changes are associated with accelerated or blastic disease. Survival studies performed to assess the prognostic significance of the various degrees of MF, showed a progressively worse life-expectancy from grade 0 to grade 3 fibrosis. Multivariate regression analysis indicated Hb level, age, number of marrow megakaryocytes (MKs), time from diagnosis as the features most significantly correlated with the degree of MF. This study demonstrates that the natural history of CGL involves a progressive increase in reticulin deposition towards severe MF, although the rate of this progression varies widely. Monitoring changes of fibrosis with sequential biopsies could give a measure of the rate of progression of the disease and help in prognostic assessment of CGL patients. Our findings also confirm that among marrow features the number of MKs is the cytological variable most significantly correlated with MF.
SummaryPhiladelphia-negative chronic myeloproliferative disorders (CMD) include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Angiogenesis is critical in the pathogenesis of PMF. We studied angiogenesis in 115 patients with CMD (23 PV, 24 ET, 46 PMF, 12 post-PV and 10 post-ET myelofibrosis) by assessment of microvessel density (MVD) in bone marrow (BM). Kruskall-Wallis analysis of variance showed that patients with PMF had significantly higher values of MVD than those with PV (P < 0AE001), ET (P < 0AE001) and controls (P < 0AE001). MannWhitney U-test demonstrated that patients with PMF at the prefibrotic stage had significantly higher MVD values than those with ET (P = 0AE02). Patients with post-PV myelofibrosis showed significantly higher MVD values than those with PV (P < 0AE001), as did patients with post-ET myelofibrosis compared with ET (P < 0AE001). In patients with CMD, the multivariate generalized linear regression model showed that the JAK2 (V617F) mutational burden (P = 0AE01), serum lactate dehydrogenase level (P = 0AE003), and anaemia (P < 0AE001) independently correlated with MVD. In summary, this study indicates that assessment of BM angiogenesis, as measured by MVD, may be a useful additional tool in the histopathological definition of CMD.
The different prevalence of BM involvement in MZL subtypes reflects their heterogeneous dissemination modalities; histology seems more sensible than FC to detect BM infiltration; development of BM involvement during follow-up is typical of EMZL.
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