Clinical and Prognostic Features of Essential Thrombocythemia: Comparison of Who 2001 Versus Who 2008/2016 Criteria in a Large Single Center Cohort
Authors: Chiatamone Ricci Sofia , Arleo Maria Antonietta , Trasarti Stefania , Santoro Cristina , Breccia Massimo , Bizzoni Luisa , Carmosino Ida , Mancini Marco , Baldacci Erminia , Molica Matteo , De Benedittis Daniela , Ciotti Giulia , Mariggiò Elena , Mohamed Sara , De Luca Maria Lucia , Pistilli Giacinta , Mancuso Annalisa , Lisi Chiara , Diverio Daniela , Vignetti Marco , Foà Robin , Latagliata Roberto , Ferretti Antonietta 
Published: October 2019

Abstract
According to the World Health Organization (WHO) 2008/2016 criteria for classification of myeloid neoplasms, a platelet (PLT) count ≥ 450X109/l, thus reduced from the previous WHO 2001 level ≥ 600 x 109/l, was considered the new PLT threshold for the diagnosis of Essential Thrombocythemia (ET).
Aim of the study was to validate in a setting of current clinical practice this important diagnostic change and compare clinical and hematological features at diagnosis and during follow-up of patients with PLT ≥600 x 109/l versus patients with PLT < 600 x 109/l.
We retrospectively analyzed data from 264 patients with ET according to WHO 2008/2016 criteria, enrolled in our center from 1/2008 to 12/2017. Patients were divided into Group A (G-A) (PLT ≥600 x 109/l at diagnosis) (199 patients - 75.4%) and Group B (G-B) (PLT ≥ 450 x 109/l < 600 x 109/l at diagnosis) (65 patients - 24.6%) and compared for clinical features at the onset, clinical course and follow-up.
Main features and commonly recognized pro-thrombotic risk factors at diagnosis of the entire cohort as well as of G-A and G-B are reported in the Table 1. Among clinical features, only the median value of leukocytes was significantly higher in G- A [9.1 x 109/l, interquartile range (IQR) 7.8-10.3 vs 7.4 x 109/l, IQR 6.0-9.6; p = 0.001]. Among pro-thrombotic risk factors, only the median cholesterol value was significantly lower in the G-A [187 mg/dl (IQR 164-220) vs 204 mg/dl (RIQ 177-238); p = 0.048]. Cytostatic treatment was administered in 175 patients (71.1%) of entire cohort at different intervals from diagnosis, with a significantly higher rate in patients of G-A (76.9% versus 49.2%, p <0.001). After a median follow-up of 37.5 months (IQR 19.8 - 60.7), 13 thrombotic events (4.9%) were recorded in the entire cohort (7 episodes in the G-A and 6 episodes in the G-B), with a 5-year Cumulative Incidence of Thrombosis (CIT) significantly higher in the G-B [79.6% (95%CI 59.6 - 99.6) versus 95.4% (95%CI 91.8 - 99.0); p=0.047] (Figure 1). No patient evolved in myelofibrotic phase, 2 patients evolved in blastic phase (BP) after 42 and 58 months, respectively [1 patient (0.5%) in the G-A and 1 patient (1.3%) in the G-B; p=0.40). At the last follow-up, 4 patients (1.5%) died (1 from BP, 1 from cerebral hemorrhage, 2 from unavailable cause), 15 (5.7%) were lost to follow-up and 245 (92.8%) are still alive and currently followed at our Institute. The 5-year Overall Survival (OS) of the entire cohort was 96.2% (IC95% 92.2 - 100), without differences between the two groups [96.3% (95% CI 92.0 - 100) in the G-A versus 96.7% (IC95% 91.7 - 100) in the G-B; p=0.898].
Our data indicate a substantial homogeneity among ET patients regardless of the PLT number at diagnosis, thus confirming the usefulness of 2008/2016 WHO diagnostic criteria. Furthermore, the counterintuitive lower CIT observed in G-A, due to a larger use of cytostatic treatments and/or to an acquired Von Willebrand phenomenon when PLT levels > 1.000 x 109/l, highlights how thrombotic risk is unrelated to PLT value and leads to consider the administration of adequate cytostatic therapy even in patients with relatively lower PLT count at diagnosis.

Disclosures
Breccia: Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria. Foà:INCYTE: Other: ADVISORY BOARD; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; CELTRION: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; ROCHE: Other: ADVISORY BOARD, Speakers Bureau; NOVARTIS: Speakers Bureau.