Vascular and Neoplastic Risk in a Large Cohort of Patients With Polycythemia Vera Roberto Marchioli, Guido Finazzi, Raffaele Landolfi, Jack Kutti, Heinz Gisslinger, Carlo Patrono, Raphael Marilus, Ana Villegas, Gianni Tognoni, and Tiziano Barbui A B S T R A C T Purpose The clinical course of polycythemia vera is often complicated by thrombosis as well as by the possible transition to myeloid metaplasia with myelofibrosis or acute myeloid leukemia. The aim of this study was to assess the rate of these complications in subjects receiving currently recommended treatments. Patients and Methods Overall, 1,638 patients from 12 countries were enrolled onto a large, prospective multicenter project aimed at describing the clinical history of polycythemia vera for the following outcomes: survival, the cumulative rate of cardiovascular death and thrombosis, the cumulative rate of leukemia, myelodysplasia, and myelofibrosis. The mean duration of the disease at entry and the duration of the follow-up were 4.9 and 2.7 years, respectively. Results The overall mortality rate of 3.7 deaths per 100 persons per year resulted from a moderate risk of cardiovascular death and a high risk of death from noncardiovascular causes (mainly hematologic transformations). Age older than 65 years and a positive history of thrombosis were the most important predictors of cardiovascular events. Antiplatelet therapy, but not cytoreductive treatment, was significantly associated with a lower risk of cardiovascular events. We found a consistent association between age and risk of leukemia, and between duration of the disease with risk of myelofibrosis. Conclusion The European Collaboration on Low-Dose Aspirin in Polycythemia Vera study documents that large international collaborative studies are feasible in this field, in which few epidemi- ologic data are available. The persistently high mortality rate from hematologic malignancies characterizes the unmet therapeutic need of polycythemic patients and suggests a priority for future studies in this disease. J Clin Oncol 23:2224-2232. © 2005 by American Society of Clinical Oncology INTRODUCTION Polycythemia vera (PV) is a chronic myelo- proliferative disorder marked by a predispo- sition to arterial and venous thrombosis, myeloid metaplasia with myelofibrosis, and acute myeloid leukemia. 1,2 Early studies in untreated patients found a high thrombosis incidence and a median survival of 18 months. 3 Phlebotomy and cytoreductive treatment by chemotherapy have reduced the number of thrombotic complications and have substantially improved survival. However, clinical studies have not provided adequate information for identifying an op- timal treatment strategy for these patients. The Polycythemia Vera Study Group (PVSG) 01 trial found the use of chloram- bucil and, to a lesser extent, 32 P, to be asso- ciated with a high leukemogenic risk, while, on the other hand, phlebotomy was less pro- tective against thrombosis. 4 Hydroxyurea, From the Consorzio Mario Negri Sud, Santa Maria Imbaro; the Catholic University School of Medicine, and the University of Rome “La Sapienza,” Rome; the Ospedali Riuniti, Bergamo, Italy; the Sahlgrenska Hospital, Göteborg, Sweden; the Department of Hematology and Blood Coagulation, University of Vienna, Austria; the Tel-Aviv Souraski Medical Center, Tel-Aviv, Israel; and the Hospital Universitario S Carlos, Madrid, Spain. Submitted July 12, 2004; accepted December 20, 2004. Supported by the European Union BIOMED 2 Program (contract No. ERBBMH4CT961433). Presented at the 45th Annual Meeting of the American Society of Hematology, San Diego, CA, December 6-9, 2003. The European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators are listed in the Appendix. Authors’ disclosures of potential con- flicts of interest are found at the end of this article. Address reprint requests to R. Marchioli, European Collaboration on Low-Dose Aspirin in Polycythemia Vera Coordinating Centre, Consorzio Mario Negri Sud, Via Nazionale, 66030 Santa Maria Imbaro, Italy; e-mail: marchioli@negrisud.it. © 2005 by American Society of Clinical Oncology 0732-183X/05/2310-2224/$20.00 DOI: 10.1200/JCO.2005.07.062 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 23  NUMBER 10  APRIL 1 2005 2224 Downloaded from jco.ascopubs.org on March 16, 2016. For personal use only. No other uses without permission. Copyright © 2005 American Society of Clinical Oncology. All rights reserved.