Long Term Anagrelid Treatment Significantly Reduces Trombotic Risk in ET Patients As Compared to Hydroxyurea + Aspirin Treatment
Authors: Péter Dombi , Árpád Illés , Judit Demeter , Lajos Homor , Zsofia Simon , Eva Karadi , Miklos Udvardy , Egyed Miklos 
Published: October 2019

Abstract
The HUMYPRON GROUP
Background: The heterogeneity of MPN care in Hungary prompted us to establish the Hungarian MPN Working Group (HUMYPRON GROUP) in year 2012.
Aims: The HUMYPRON GROUP created our MPN Registry in 2013, the aims were: (1) to gain epidemiological, diagnostic, therapeutic data, to follow up complications and disease transformations. (2) to investigate the adherence to the WHO/2008 diagnostic criteria and to the Landolfi therapeutic guidelines, to gain insight into vascular and haematological complications. (3) to try to identify crucial issues and possible gaps, and promote internationally accepted, standard care in MPN.
Methods: The questionnaire had been thoroughly updated regarding the 2008 WHO diagnostic criteria (morphology, mutations, etc.) with focus on complications, risk stratification and treatment. The electronic platform can be continuously updated as needed by our steering committee (new molecular results e.g. calreticulin mutations can be included). All haematologists using the system are entitled to initiate search and association analysis. Our MPN Registry is legally permitted by our authorities (ETT-TUKEB) .The data entry was started in 2014. The centers entered the data of all the essential thrombocythaemia (ET), polycythaemia vera (PV)PV and idiopathic myelofibrosis (IMF) patients they had diagnosed and treated.
In the present work we have compared the outcome of ET patients treated with either with anagrelid (ANA) or with Hydroxyurea (HU) + aspirin (ASA) based on registry data.
Results: During the first active year of the Hungarian MPN Registry 15 of our major or smaller haematological centers provided patient data, all together reaching the evaluable ET patient number of 350. Because of the method we used entering the data, (all patients of a center) a long follow up period was gained, allowing us analyzing effectiveness of different treatment modalities. We have found the data of 141 ET patients, treated with HU + ASA, and 139 ET patients, treated with anaghrelid +/- ASA. There were 65 thrombotic events among the HU+ASA treated group ,while only 25 among the anagrelid group. The major vascular events were the same, but the minor events were different. There were 2 hemorrhagic complications in HU group and 3 in anagrelid group. The male/female ratio, the median age, the follow up period, the Landolfi risk results, the JAK2V617F positivity ratio were comparable between the two groups. We found a significant difference in the frequency of thrombotic events in favour of the anagrelid treatment arm. (Table 1)
Table 1. Comparison of Anagrelid versus Hydroxyurrea + aspirin treated ET patients ET/ANA (n=139) ET/HU+ASA (n=141) Gender Male 47 48 Female 92 93 Age et the time of diagnosis (years) Median 60 63 Minimum 25 27 Maximum 92 89 Follow-up time (months) 83 78 JAK V617F mut + (%) 57.0 59.0 Risk stratification according Landolfi (median) 4.56 4.59 Thrombotic events p: 0,000473 25 63 Arterial minor 6 28 Arterial major 2 2 Venous minor 5 27 Venous major 12 6 Major bleeding events 3 2 Progression 5 4 Myelofibrosis 4 3 MDS/AML 0 1 Solid tumor 1 0
Anagrelid was found to be significantly superior when total thrombotic risk and the frequency of minor thrombotic events was evaluated.
The Chi-square statistic is 12.2199. The p value is 0.000473. This result is significant at p< 0.05
Summary/Conclusion:
1. We have created a national MPN Registry covering a large part of Hungary. The database is operational, online, user friend, easily adjustable to the new professional needs. It is convenient for complex search, correlation and other multiparametric analysis. The data collected so far are in concert with the international epidemiological data.
2. Our first evaluation of two treatment modalities of ET reached a very interesting result. The earlier publications showed superiority of HU based treatments over anagrelid. Here we report an opposite result, based on the data of a large number of ET patients and a very long follow up period. When comparing the frequency of the major thrombotic events both treatments proved equally effective, but anagrelid was found to be significantly superior when total thrombotic risk and the frequency of minor thrombotic events was evaluated.

Disclosures
Judit: Semmelweis University First Department of Internal Medicine, Division of Haematology: Employment, Other: advisory board BMS, Roche, Novartis, Amgen.