Retrospective Analysis on 290 Patients with Polycythemia Vera Referred to a Single Transfusion Centre: Diagnosis Revision According to WHO Criteria and Evaluation of Survival and Complications According to Prognostic Factors and Treatment
Authors: Venturino Ermanno , Ferrero Dario , Crisà Elena , Bazzan Mario , Ciocca Ausilia , Sorasio Roberto , Giai Valentina , Genuardi Mariella , Boccadoro Mario 
Published: April 2020

Abstract
Polycythemia vera (PV) is a myeloproliferative disorder strongly related to a mutated state of JAK2 tyrosine kynase. Several guide-lines have been published on diagnostic criteria and disease management. However, it is not well known if these recommendations are actually followed in the common clinical practice. Moreover, the recent large ECLAP study (Di Nisio et al.: Br J Haematol 2007) questioned the former strong recommendation of keeping the hematocrit (Hct) value below 0.45. We analysed 290 patients with a PV diagnosis made from January 1995 to December 2006 in different hematological institutions and referred to a single transfusion centre for phlebotomy. Among the whole casistics, 210 patients only satisfied 2001 or 2007 WHO diagnostic criteria for PV. This selected group of patients underwent further evaluation of clinical outcome. JAK2 V617F mutation was found in 80/83 of these patients. Median follow up from diagnosis was 68 months (range 13–161). The 210 patients included 115 males and 95 females with a median age of 65 years (range 18–92). Known risk factors at diagnosis comprehended history of previous thrombosis in 34 and concomitant cardiovascular risk factors (diabetes, smoking habit, hypertension, dyslipidemia) in 124 patients. According to the thrombotic risk stratification (Finazzi et al.: Blood 2005), 36 patients were in the low risk group, 29 in the intermediate one and 145 in the high risk group. All patients received phlebotomy at least in the first month from diagnosis. Eighty patients proceeded with phlebotomy only, whereas 130 also received a cytoreductive treatment for at least 6 months. Almost all patients (205: 98%) received either anti-platelets (195) and/or anti-coagulant (30) therapy. The main cytoreductive treatment was hydroxyurea (HU), used by 127 (97%) patients. In particular, HU was the only cytoreductive agent for 107 patients. Other drugs included pipobroman (18 patients), busulfan (5 patients), alpha interferon (2 patients) and 6-thioguanine (1 patient), used for intolerance or suboptimal response to HU. A thrombotic event was observed at diagnosis in 21 patients (10%). A correlation was observed between thrombosis at diagnosis and both thrombocytosis &gt; 600 × 109/l (p: &lt;0.001) and known cardiovascular risk factors (p: 0.03). During follow-up, seventeen patients died. Survival rate was 91.5% at the median follow-up of 68 months and is projected to reach 84% at 13 years. Overall survival was negatively influenced by age at diagnosis &gt; 65 years (p: &lt; 0.001), history of thrombosis before diagnosis (p: 0.05) and high risk score according to thrombotic risk stratification (p: 0.05). Forty-five patients (21%) displayed post-diagnosis thrombotic events at a median time of 41 months, which correlated to age at diagnosis &gt; 65 years (p: 0.006) and high thrombotic risk score (p: 0.04). Leukemic evolution occurred in 4 patients (2%), while secondary myelofibrosis and non-hematological neoplasia were observed in 8 and 11 patients, respectively. Chemotherapy administration did not affect neither overall nor thrombosis-free survival but correlated to neoplastic events (p: 0.05). Median Hct during follow up was kept at the recommended value &lt; 0.45 in 31 patients only (15%). Sixty-three % of patients maintained a median Hct value between 0.45 and 0.48 whereas 21.5 % had median Hct value &gt; 0.48. A Hct value &lt; 0.48 positively affected overall (p: 0.02) but not thrombosis-free survival. A possible advantage of keeping Hct value &lt; 0.45 could not be demonstrated due to the small number of patients in this group. In conclusion, diagnostic procedures were not found adherent to WHO indications in 80/290 (27%) patients with hypothetical PV diagnosis and in most of patients the Hct value could not be maintained below the recommended value. The importance of JAK2 evaluation as a diagnostic criteria was further underlined by the detection of V617F mutation in 96 % of the screened patients with a confirmed diagnosis of PV. Our casistics confirmed the role of known prognostic factors as age, previous thrombosis or concomitant cardiovascular risk factors, while the optimal Hct value during follow up (&lt; 0.45 or &lt; 0.48) and the true advantage of cytoreductive treatments remain to be established.