The present study describes clinicopathological criteria to distinguish the 5 sequential stages proposed by Wasserman et al in the natural history of newly diagnosed PV patients. The European Working Group on MPD (EWG.MPD) extended and modified the PVSG diagnostic criteria of PV by including bone marrow histopathology. From the results of prospective randomized studies in PV it became evident that new clinical trials in previously untreated PV patients should focus on comparing
interferon-alpha, a non-leukemogenic approach, versus a potential leukemogenic myelosuppressive treatment modality.
Hydroxyurea appears to be the least leukemogenic myelosuppressive agent in long-term prospective clinical PV-studies extending observation periods of more than 10 years. The rational for using IFN-alpha as a first-line treatment option in newly diagnosed PV-patient include its effectiveness to abate constitutional symptoms and to induce a complete remission thereby avoiding phlebotomy,
iron deficiency, and macrocytosis associated with
hydroxyurea. Moreover IFN-alpha may prevent or delay the development of postpolycythemic
myelofibrosis if used early in the course of the disease. Clinicians will be reluctant to postpone the use of
hydroxyurea in early stage PV as long as a conservative approach using phlebotomy aiming at a hematocrit below 0.45, plus low-dose
aspirin for the control platelet function or
anagrelide for the control platelet number is used to keep the patient healthy. Low-dose
aspirin will prevent the microvascular thrombotic complications of
thrombocythemia associated with PV in remission after phlebotomy, but lacks myelosuppressive activity. Control of megakaryocyte maturation and reduction of platelet production to normal (<400 x 10(9)/l) by relatively low doses of
anagrelide will predict a significant reduction of vascular complications in the early stages of PV, may prevent progression to
myelofibrosis during follow-up of PV and very probable will postpone the use of
hydroxyurea treatment for controlling the platelet count in PV. Large scale randomized clinical trials in PV are proposed, which should aim not only for clinical and hematological response, safety, efficacy, but should also assess toxicity, the need for phlebotomy and whether the development of progressive disease such as
splenomegaly,
pruritus, myelofibrotic
myeloid metaplasia, spent phase, myelodysplasia and acute
leukemia can be delayed or prevented by IFN-alpha as compared to a conservative approach of phlebotomy plus low-dose
aspirin or
anagrelide followed by
hydroxyurea when signs of myeloproliferative activity became evident.