Page 23 - 2020_08-Haematologica-web

An agenda for future research projects in polycythemia vera and essential thrombocythemia
Ferrata Storti Foundation
Haematologica 2020 Volume 105(8):1999-2003
Tiziano Barbui,1 Alessandro Maria Vannucchi,2 Paola Guglielmelli,2 Valerio De Stefano3 and Alessandro Rambaldi4
1FROM Research Foundation, Papa Giovanni XXIII Hospital, Bergamo; 2Center of Research and Innovation of Myeloproliferative Neoplasms (CRIMM), Azienda Ospedaliera Universitaria Careggi and Department of Experimental and Clinical Medicine, University of Florence, Florence; 3Section of Hematology, Department of Radiological and Hematological Sciences, Catholic University and Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome and 4Department of Oncology and Hematology, University of Milan, Milan and Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
Introduction
The clinical course of essential thrombocythemia (ET) and polycythemia vera (PV) is characterized by an increased incidence of vascular complications and a tendency to progress to myelofibrosis (MF) or acute myeloid leukemia (AML). Over the past decade, new molecular and clinical knowledge in ET and PV has led to a significant improvement in the diagnostic, prognostic and therapeutic processes. Despite these advancements, many uncertainties remain concerning aspects of clinical decision-making. We identified some unmet needs in clinical practice and research that urgently require new scientific initiatives. For each of these, we reviewed the most significant existing evidence and made proposals for translational and clinical investigations. We acknowledge that several other clini- cally relevant unmet needs in the management of patients with PV and ET remain. These could not be addressed due to space constrains, and include, above all, prediction of evolution to secondary forms of myelofibrosis, identification of genetic predictors of survival and of specific subgroups of patients to include in intervention trials with novel drugs that are claimed to modify disease course.
Should we look for new diagnostic and prognostic criteria to distiguish pre-fibrotic myelofibrosis and essential thrombocythemia?
One of the major changes introduced by the 2016 World Health Organization (WHO) classification is the distinction between so called “true” ET and pre-fibrot- ic PMF. Insights from large series from reference institutions suggest that the pro- portion of ET patients who would be reclassified as pre-PMF according to these criteria may be as high as 15-30%.1,2
Although some clinical and hematologic traits cluster preferentially with pre- PMF, with the exception of histopathology, no unique distinctive criterion con- tributes to diagnosis. The same holds true for the mutation landscape, since only a slight increase in CALR mutation frequency is observed in pre-PMF patients. On the other hand, there may be important differences in terms of disease course, clinical complications and overall prognosis. First, the rate of thrombosis seems to be quite similar in pre-PMF and ET (2% patient-years in both conditions).1,3,4 Risk variables associated with thrombosis appear to be similar in pre-PMF and ET, as supported by the results of a recent study where the International Prognostic Score of Thrombosis for Essential Thrombocythemia (IPSET-thrombosis) reliably predicted thrombosis in patient with pre-PMF.5 In contrast, bleeding episodes may be more frequent in pre-PMF as compared to ET.6 Of note, according to large retrospective series, the most distinctive feature between the two diseases is sur- vival, uniformly worse in pre-PMF (ranging from 10.5 to 14.7 years) compared to ET (14.7-21.8 years) in which it was rather similar to the standardized European life expectancy.7,8 No specific risk model for survival has yet been developed for pre-PMF; whether that developed for the WHO 2008 definition of ET is proving satisfactory also for pre-PMF remains to be addressed.8 The same debate applies also to the recent molecular integrated scores MIPSS-70, that included fibrosis grade 1 versus grade 2/3 (the latter is one distinctive feature of overt-PMF vs. pre- MF) as a significant variable for survival.9 Therefore, since expected survival is the key issue to discuss with a patient newly diagnosed with pre-PMF, acquiring such
Correspondence:
TIZIANO BARBUI
tbarbui@fondazionefrom.it.
Received: March 4, 2020. Accepted: April 14, 2020. Pre-published: May 28, 2020.
doi:10.3324/haematol.2019.246207
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/8/1999
©2020 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
haematologica | 2020; 105(8)
1999
PERSPECTIVE ARTICLE