Page 77 - 2019_12-Haematologica-web

Myeloproliferative Neoplasms
Clinical outcomes under hydroxyurea treatment in polycythemia vera: a systematic review and meta-analysis
Ferrata Storti Foundation
Haematologica 2019 Volume 104(12):2391-2399
Alberto Ferrari,1 Alessandra Carobbio,1 Arianna Masciulli,1 Arianna Ghirardi,1 Guido Finazzi,2 Valerio De Stefano,3 Alessandro Maria Vannucchi4 and Tiziano Barbui1
1FROM Research Foundation, ASST Papa Giovanni XXIII, Bergamo; 2Hematology Division, Papa Giovanni XXIII Hospital, Bergamo; 3Institute of Hematology, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome and 4CRIMM-Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi and Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
ABSTRACT
Hydroxyurea is the standard treatment in high-risk patients with polycythemia vera. However, estimates of its effect in terms of clin- ical outcomes (thrombosis, bleeding, hematologic transformations and mortality) are lacking. We performed a meta-analysis to determine the absolute risk of events in recent cases of patients under hydroxyurea treat- ment. We searched for relevant articles or abstracts in the following data- bases: Medline, EMBASE, clinicaltrials.gov, WHO International Clinical Trials Registry, LILACS. Sixteen studies published from 2008 to 2018 reporting number of events using World Health Organization diagnosis for polycythemia vera were selected. Through a random effect logistic model, incidences, study heterogeneity and confounder effects were estimated for each outcome at different follow ups. Overall, 3,236 patients were ana- lyzed. While incidences of thrombosis and acute myeloid leukemia were stable over time, mortality and myelofibrosis varied depending on follow- up duration. Thrombosis rates were 1.9%, 3.6% and 6.8% persons/year at median ages 60, 70 and 80 years, respectively. Higher incidence of arterial events was predicted by previous cardiovascular complication. Leukemic transformation incidence was 0.4% persons/year. Incidence of transforma- tion to myelofibrosis and mortality were significantly dependent on age and follow-up duration. For myelofibrosis, rates were 5.0 at five years and 33.7% at ten years; overall mortality was 12.6% and 56.2% at five and ten years, respectively. In conclusion, we provide reliable risk estimates for the main outcomes in polycythemia vera patients under hydroxyurea treat- ment. These findings can help design comparative clinical trials with new cytoreductive drugs and prove the feasibility of using critical end points for efficacy, such as major thrombosis.
Introduction
Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) characterized by clonal proliferation of the erythroid, myeloid, and megakaryocyte lineages. This disease is recognized for its distinct molecular profile (JAKV 617F mutation) and has a characteristic natural history marked by high frequency of thrombosis and a ten- dency to transform into acute myelogenous leukemia (AML) or myelofibrosis (MF). The first step in approaching an individual patient with PV is to identify the poten- tial risk of developing major thrombotic or hemorrhagic complications. In patients under 60 years of age, carrying only reversible or controllable cardiovascular risk factors and without prior history of thrombosis, phlebotomy (PHL) or low-dose aspirin are recommended. Cytoreductive therapy with either hydroxyurea (HU), a
Correspondence:
TIZIANO BARBUI
tbarbui@asst-pg23.it
Received: March 7, 2019. Accepted: May 20, 2019. Pre-published: May 23, 2019.
doi:10.3324/haematol.2019.221234
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/12/2391
©2019 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 | 2019; 104(12)
2391
ARTICLE