ISSN: ISSN: 2329-8790
The PVSG defined in 1975 the myeloproliferative disorders (MPD) essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) or agnogenic myeloid metaplasia (AMM) are three distinct disease entities with regard to clinical manifestations, natural history and outcome in terms of life expectancy. The European Clinical and Pathological (ECP) criteria demonstrated that fibroblast proliferation in PVSG defined PMF and post-ET and post-PV myelofibrosis is polyclonal indicating that myelofibrosis (MF) is secondary in all variants of myeloproliferative syndromes. By including bone marrow histopathology the ECP defined between 1998 and 2000 the prefibrotic MPDs ET, PV and primary megakaryocytic granulocytic myeloproliferation (PMGM) as three distinct myeloproliferative disease (MPD) entities. Clinical, hematological and morphological characteristics, in particular megakaryocytopoiesis and bone marrow cellularity, reveal diagnostic features, which enable a clear-cut distinction between two prefibrotic MPDs ET and PV versus PMGM as the third distinct MPD entity. Life expectancy is normal in normocellular ET, normal during the first ten years and compromised during the second ten years follow-up in PV, but shortened in the prefibrotic hypercellular stage of PMGM. First line treatment options anno 2000 were control of platelet function with low-dose aspirin in ET, low-dose aspirin on top of phlebotomy in PV and a wait and see strategy in the prefibrotic and fibrotic stages of PMGM. Pegylated Interferon (IFN) was proposed in between 1998 and 2000 as the first line non-leukemogenic treatment option in prodromal PV and early or classical stages of PV. Because of its leukemogenicity hydroxyurea should be postponed as long as possible and to be used in progressed MPD restricted to the hypercelluar stages of PV and ET for the treatment of uncontrolled thrombocytosis, leukocytosis splenomegaly and constitutional symptoms. These conclusions could be confirmed in the Dutch updates since 2000, are still valid and did not change significantly between 2008 and 2018 due the discovery of JAK2, CALR and MPL driver causes of MPN between 2005 and 2013.