Clinical Features of Idiopathic Erythrocytosis Compared to Polycythemia Vera JAK-2 V617F Positive and Negative Patients
Authors: Latagliata Roberto , Tafuri Agostino , Spadea Antonio , Ferretti Antonietta , Diverio Daniela , Breccia Massimo , D'Andrea Mariella , Andriani Alessandro , Montanaro Marco , Cedrone Michele , Montefusco Enrico , Rago Angela , Olimpieri Odoardo Maria , Bagnato Antonino , Biondo Francesca , Vozella Federico , Cantonetti Maria , Petti Maria Concetta , Alimena Giuliana 
Published: October 2019

Abstract
Abstract 5172
The introduction of JAK-2 V617F mutation in the diagnostic process of patients with erythrocytosis has led to a better definition of Polycythemia Vera (PV) patients, who had the mutation in > 90% of cases: however, in the real-life many patients with otherwise unexplained Hb and Ht elevation and lack of JAK-2 V617F mutation are located in the gray zone of the so-called Idiopathic Erythrocytosis (IE). In order to highlight clinical features of patients with IE, we revised 247 patients with primary erythrocytosis (i.e. excluding cases with respiratory and/or severe cardiovascular diseases) diagnosed in 2 Hematological Institutions in Rome from 6/1985 to 12/2010 with a evaluable JAK-2 mutational status at diagnosis or during the follow-up. Were considered as “PV JAK-2 positive” all patients with presence of mutation V617F at diagnosis or during follow-up. Among the patients who resulted JAK-2 V617F negative, were considered as “PV JAK-2 negative” all patients classifiable as PV according to PVSG criteria (if diagnosed before 1/2002) or WHO 2002 criteria (if diagnosed after 1/2002): the remaining patients were classified as “IE”. With these criteria, 181 patients (73.2%) were PV JAK-2 positive, 26 (10.5%) PV JAK-2 negative and 40 (16.3%) IE: the main clinical features of these 3 groups at diagnosis and during the course of disease are summarized in the table.PV JAK-2 positivePV JAK-2 negativeIENo of patients1812640Male87 (48%)22 (84%)38 (95%)Median age yrs (IR)59.3 (49.7–68.5)47.9 (42.6–64.5)57.8 (44.2–65.9)Median WBC x 109/l (IR)10.0 (8.4–13.0)10.6 (6.3–12.5)7.3 (6.4–8.3)Median PLTS x 109/l (IR)481 (349–651)214 (189–344)205 (165–236)No with palpable spleen63 (35.0%)7 (27.0%)2 (5.0%)Previous thrombosis29 (16.0%)2 (7.6%)1 (2.5%)Thrombosis during disease32 (17.7%)1 (3.8%)4 (10.0%)Fibrotic/Blastic evolution12 (6.6%)00
Comparing the 3 groups for the above features, there was a very significative (p<0.001) male predominance in both IE and PV JAK-2 negative vs PV JAK-2 positive patients: in addition, patients with PV JAK-2 negative were younger (p=0.017). Compared to patients with IE, myeloproliferative features were significantly more prominent in patients with PV JAK-2 positive [higher WBC (p<0.001) and PLTS (p<0.001) median values and higher number of patients with spleen enlargement (p<0.001)]; furthermore, also patients with PV JAK-2 negative had higher WBC median value (p=0.008) and more cases with spleen enlargement (p=0.007) compared to patients with IE, but not higher PLTS median value (p=0.166). Previous thrombotic events were more frequent in PV JAK-2 positive patients vs patients with IE (p=0.032), while no difference was revealed among the 3 groups as to thrombotic events during follow-up and fibrotic/blastic evolution. In conclusion, the 3 groups were based on simple clinical data and seem to differ in some important baseline characteristics: the groups of PV JAK-2 negative and IE, however, seem still quite heterogeneous and deserve further and more accurate biological (exon 12 mutations) as well as clinical (venous blood p50 measurement) insights. The role of male gender and its predominance in unexplained erythrocitosis JAK-2 negative remain to be clarified.

Disclosures:
No relevant conflicts of interest to declare.