Polycythemia vera: historical oversights, diagnostic details, and therapeutic views.

Polycythemia vera (PV) is a relatively indolent myeloid neoplasm with median survival that exceeds 35 years in young patients, but its natural history might be interrupted by thrombotic, fibrotic, or leukemic events, with respective 20-year rates of 26%, 16%, and 4%. Current treatment strategies in PV have not been shown to prolong survival or lessen the risk of leukemic or fibrotic progression and instead are directed at preventing thrombotic complications. In the latter regard, two risk categories are considered: high (age >60 years or thrombosis history) and low (absence of both risk factors). All patients require phlebotomy to keep hematocrit below 45% and once-daily low-dose aspirin, in the absence of contraindications. Cytoreductive therapy is recommended for high-risk or symptomatic low-risk disease; our first-line drug of choice in this regard is hydroxyurea but we consider pegylated interferon as an alternative in certain situations, including in young women of reproductive age, in patients manifesting intolerance or resistance to hydroxyurea therapy, and in situations where treatment is indicated for curbing phlebotomy requirement rather than preventing thrombosis. Additional treatment options include busulfan and ruxolitinib; the former is preferred in older patients and the latter in the presence of symptoms reminiscent of post-PV myelofibrosis or protracted pruritus. Our drug choices reflect our appreciation for long-term track record of safety, evidence for reduction of thrombosis risk, and broader suppression of myeloproliferation. Controlled studies are needed to clarify the added value of twice- vs once-daily aspirin dosing and direct oral anticoagulants. In this invited review, we discuss our current approach to diagnosis, prognostication, and treatment of PV in general, as well as during specific situations, including pregnancy and splanchnic vein thrombosis.

Identification of significant geographic clustering of polycythemia vera cases in Montreal, Canada.

BACKGROUND: Polycythemia vera (PV) is a chronic myeloproliferative neoplasm associated at times with debilitating symptoms and a significant mortality rate. Understanding the demographics, epidemiology, and geography of this disease may provide further insight into important risk factors associated with its development. The objective of this study was to analyze patient demographics, incidence, and mortality rates, as well as the geographic distribution of PV patients in Canada between 1992 and 2010. METHODS: This study was achieved by analyzing the Canadian Cancer Registry, Le Registre Québécois du Cancer, and the Canadian Vital Statistics patient databases. RESULTS: A total of 4645 patients were diagnosed with PV between 1992 and 2010. While the annual incidence rate of this cancer fluctuated in Canada, mortality rate analysis indicated a decreasing trend. Geographically, PV incidence rates were notably elevated in the province of Quebec compared with the Canadian average. Further analysis of high-incidence forward sortation areas indicated a striking clustering of cases in the H4W region encompassing the Côte-Saint-Luc borough of Montreal, with an incidence of 102.97 (95% confidence interval, 75.11-137.79) cases per million per year, which is >13 times the national average. CONCLUSION: The residential area of Côte-Saint-Luc is an important PV cluster in Canada, with high concentration of retirement homes and geriatric hospices. Also, Jewish residents comprise >60% of the population in this neighborhood. These findings suggest that an older age and, potentially, an inherent genetic predisposition may be implicated in the pathogenesis of this malignancy. This study provides a comprehensive overview of PV burden/geographic distribution of cases in Canada.

Polycythemia vera: plethora, from prehistory to present.

The term polycythemia (literally, "many blood cell disease") and its obsolete synonym, erythremia, postdate Robert Hooke's 17th century discovery of cells, but the concept of a clinically problematic excess of blood was formulated in antiquity. Observation of plethoric patients by clinicians of the Hippocratic school informed the classical humoral framework that dominated theoretical constructs of human disease for more than a thousand years. In the golden era of disease description at the end of the 19th century, the idiopathic entity polycythemia rubra vera (PRV) was first described and distinguished from secondary and relative polycythemia (red cell excess not caused by a primary bone marrow disorder, and artifactual red cell excess caused by plasma volume contraction, respectively). This review traces some of the principal events in the history of polycythemia vera (PV) as a discrete clinical entity.

Polycythemia vera: a retrospective and reprise.

This article, by two of the late John H. Lawrence's fellows of the 1940s, traces the development of the knowledge of polycythemia vera from Vaquez, who wrote the first description of this disease, and Osler, who recognized it as "a new clinical entity," through John H. Lawrence and the use of 32P as a treatment for polycythemia vera, to the formation of French and Italian polycythemia study groups. In particular, the history of polycythemia vera after the Second World War, and its more recent history, can be traced through the development of an algorithm for evaluating an elevated hematocrit and the development of the first (O1) protocol of the Polycythemia Vera Study Group (PVSG), a randomized trial of the efficacy of 32P, chlorambucil, and phlebotomy for treating polycythemia vera. It was in 1948, only 9 years after the first use of 32P for treating polycythemia vera, that Byron Hall reported the occurrence of acute leukemia following this use of the isotope. This led to the formation of the PVSG. After completing enrollment of patients in the first protocol of the PVSG, an attempt to find a replacement for 32P as a myelosuppressive agent led to the testing of hydroxyurea as a putative non-leukemogenic drug for this purpose. However, the use of hydroxyurea for treating polycythemia vera is coming into question, as is the ability to maintain patients with phlebotomy alone. The PVSG as such no longer exists as an operational group; its files are maintained at the Mount Sinai School of Medicine in New York City. However, the French group created for the study of polycythemia vera has had a consensus conference, and the Italian group has developed a low-dose aspirin protocol for treating the disease.