The Impact of Clinicopathological Studies on Staging and Survival in Essential Thrombocythemia, Chronic Idiopathic Myelofibrosis, and Polycythemia Rubra Vera

Abstract

In chronic myeloproliferative disorders (MPDs), varying results regarding staging of disease and assessment of outcome have been reported. Risk classification is mainly based on clinical data; however, in those disorders associated with an elevated platelet count, discrimination of (true) essential thrombocythemia (ET) may be difficult without the possibility to recognize characteristic histopathological bone marrow patterns according to the World Health Organization (WHO) guidelines. Patients with ET reveal no relevant reduction of life expectancy and the impact of disease is significantly higher in elderly patients, especially in chronic idiopathic myelofibrosis (IMF) and polycythemia rubra vera (PV). In high-risk ET, the overall incidence of myelofibrotic transformation after 36 months of follow-up is 2.8% when considering the Polycythemia Vera Study Group guidelines. In contrast, classification according to WHO fails to show a relevant transformation into myelofibrosis either by clinical or morphological standards in (true) ET. Early stages of IMF show a more favorable outcome, but in multivariate risk classification, signs of myeloid metaplasia have the most important impact on prognosis. In PV, the risk for thrombosis increases with age, and furthermore, signs of generalization are generally associated with a worsening of prognosis. It has been shown that examination of bone marrow specimens enhances the diagnostic reliability and also enables the recognition of evolving myelofibrotic transformation in MPDs.

How to manage children and young adults with myeloproliferative neoplasms

“…The onset of the MPNs is often a very slowly advancing process and both in the WHO-defined PV and ET, disease-specific survival (loss in life expectancy) is not substantially different from that of a control population, especially in younger adults. 14 PMF is a more serious disease with expected median observed survival of about 6 years, 15 whereas in prefibrotic myelofibrosis median survival is about 10 years. 14 Information on the genetic abnormalities most commonly encountered in MPNs has to be explicitly discussed.…”

“…14 PMF is a more serious disease with expected median observed survival of about 6 years, 15 whereas in prefibrotic myelofibrosis median survival is about 10 years. 14 Information on the genetic abnormalities most commonly encountered in MPNs has to be explicitly discussed. The concern regarding the possibility that MPNs can be heritable should be addressed in this context by emphasizing that the vast majority of MPN cases are sporadic and that the genetic mutation of JAK2 is not a predisposing factor.…”

“…14 The International Prognostic Scoring System (IPSS) for classical-advanced PMF uses five independent predictors of inferior survival (age 465 years, hemoglobin o10 g/100 ml, leukocyte count 425 Â 109/l, circulating blasts 41% and presence of constitutional symptoms) to stratify patients into low, intermediate-1, intermediate-2 and high-risk categories based on the presence of 0, 1, 2 or 43 risk factors, respectively; the corresponding median observed survivals are estimated at 135, 95, 48 and 27 months. 15 On the other hand, it has to be tested whether this International Prognostic Scoring System may be also applicable on patients with early PMF that infrequently present with constitutional symptoms.…”

Prodromal myeloproliferative neoplasms: The 2008 WHO classification

“…This trial investigates the effect of hydroxyurea versus anagrelide therapy, but particularly their influence on progression into MF in 809 patients with ET at high risk for vascular events. To highlight the impact of accurate morphological diagnosis on the development of MF, a corresponding multi-center study on 539 patients with high risk ET has been performed [128]. Clinical data at onset were in explicit accordance with the UK-PT 1 trial [129] as well as histological definitions that included manifest MF with at least Grade 2 on a threegraded scale [121].…”

“…Additional requirements were an increase in one grade in less than 12 months of follow-up together with at least two of the following: increase in spleen size of about 3 cm, unexplained decrease of hemoglobin, immature precursors in the peripheral blood and tear-drop poikilocytosis on the blood smear [27]. The overall incidence of myelofibrotic transformation after 36 months of observation time was 2.8% [128,129] according to the PVSG criteria [5,21], thus confirming the results of the UK-PT 1 study which reported a corresponding complication in 2.6% (21 of the 809 patients) [27]. However, when applying the WHO criteria for ET [1,2], not a single case revealed a transformation into MF either by clinical or morphological standards during observation time [128,129].…”