Treatment Options for Essential Thrombocythemia and Polycythemia Vera

Alessandro M. Vannucchi; Paola Guglielmelli; Lisa Pieri; Elisabetta Antonioli; Alberto Bosi


Expert Rev Hematol. 2009;2(1):41-55. 

In This Article


Polycythemia vera and essential thrombocythemia are the most common chronic myeloproliferative neoplasms; their molecular basis has been appreciated only recently and is briefly discussed in this article. Major causes of morbidity and mortality are represented by arterial and venous thrombosis, as well as by evolution to myelofibrosis or transformation to acute leukemia. Therapy is currently aimed at reducing the rate of thrombosis without increasing the risk of hematologic transformation that might be caused by exposure to cytotoxic drugs. A risk-oriented approach is employed for stratifying patients to the most appropriate therapeutic options. However, results of clinical trials with interferon, and the expected effects of novel drugs selectively targeting the abnormal pathways that are involved in the clonal myeloproliferation, are pushing therapeutic goals from disease control only to cure. These different issues, and current recommendations for treatment, will be discussed in the review.

Polycythemia Vera and Essential Thrombocythemia: 'Classic' Chronic Myeloproliferative Disorders

Polycythemia vera (PV) and essential thrombocythemia (ET), together with primary myelofibrosis (PMF), represent the classic, Philadelphia chromosome (Ph')-negative chronic myeloproliferative disorders (CMPDs). Their grouping together was forecasted in 1951 by William Dameshek based on similarities in their clinical phenotype and the hypothesis that they reflected a global myeloproliferation due to some unknown stimuli.[1] The 2001 WHO classification of tumors of hematopoietic tissues formally recognized a family of CMPDs in which PV, ET and idiopathic myelofibrosis (now recognized as primary myelofibrosis)[2] were included together with unusual entities characterized by abnormal proliferation of eosinophils or other ill-defined 'unclassified CMPDs'.[3]

The discovery of specific molecular abnormalities associated with the myeloproliferative disorders (MPDs) in the last 3 years[4] has produced a body of information that has contributed to simplifying and making more accurate the diagnostic approach and has, ultimately, resulted in a revisitation of the original WHO statements.[5] In the 2008 WHO classification of myeloid neoplasms, which has been published recently in its 4th Edition,[6] these disorders have been renamed 'myeloproliferative neoplasms' (MPNs) to better signify the neoplastic nature of the myeloproliferation; they are listed in Box 1. The 'classic' MPNs, such as PV, ET and PMF, should be distinguished from other 'nonclassic' myeloproliferative conditions, such as chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia not otherwise specified (CEL-NOS), mastocytosis and unclassifiable forms of MPNs (MPN-U), as well as from BCR-ABL-positive chronic myelogenous leukemia (CML).[7]

The classic MPNs are among the most frequent hematologic neoplasia. According to a recent survey, based on the North American Association of Central Cancer Registries, the average 2001-2003 annual, age-adjusted, cumulative rate for PV, ET and PMF was 2.1 per 100,000.[8] Furthermore, owing to their relatively smooth clinical course compared with other hematological neoplasia, it is not unlikely that many cases of PV or ET are not reported to registries or even go undiagnosed; therefore, the true occurrence of these disorders might be even significantly higher. The MPNs usually affect the adult-elderly population; in the previously cited US study, the occurrence rate was as high as 13.3 per 100,000 among individuals aged older than 80 years.