Are Outcomes Worse For Patients With Polycythemia Vera compared to Polycythemia Of Unknown Cause? – a Retrospective Analysis Of Single Institution Patient Cohorts
Authors: Chacko Joseph , Boyce Sara , Killick Sally , Rachel Hall , McCarthy Helen , Renata Walewska , Wallis Louise 
Published: October 2019

Abstract

Background
The JAK2 V617F mutation is present in almost 95% of patients with Polycythemia Vera (PV). Prior to the discovery of this mutation, red cell mass and plasma volume measurement to establish the presence of true erythrocytosis was required first, before the diagnosis could be confirmed using other criteria. The revised WHO criteria no longer mandate this. Besides, access to this test is restricted in our region, due to non-availability of radio-isotopes. We previously showed the utility of early JAK2 mutation screening when used with history, physical examination, oxygen saturation, complete blood count, blood film examination, splenomegaly, serum erythropoietin, phlebotomy trial, bone marrow biopsy and, when available, red cell mass studies.

Patients
Between 2002 and 2006 we screened 231 consecutive patients referred to our institution with raised hemoglobin and hematocrit for JAK2 mutation. PV was diagnosed in 27 patients. Polycythemia of unknown cause (idiopathic) was identified in 40 patients after excluding patients with transient polycythemia and secondary polycythemia due to hypoxia, sleep apnoea, excessive smoking, alcohol abuse, renal disease, androgens or inherited causes. All PV patients were assessed at 3-6 monthly intervals from diagnosis until death or to present day. All idiopathic polycythemia patients were assessed at 6-12 monthly intervals until discharge, death or to present day. Patients with idiopathic polycythemia were discharged from follow-up when their hematocrit returned to normal range without any interventions for at least 12 months. All patients received thromboprophylaxis with aspirin or vitamin K antagonists as appropriate unless contra-indicated.

Results
Of 27 PV patients, 15 were males and 13 females. The median age at diagnosis was 69 years (range 21-88 years). Leucocytosis was present at diagnosis in 14 and thrombocytosis in 15 patients. Patients were treated with phlebotomy to a target hematocrit<0.45 (18 patients), hydroxycarbamide (16 patients), alpha-interferon (1 patient) and busulfan (1 patient). Nine patients were treated with phlebotomy alone and the remainder (18 patients) started with phlebotomy and switched to cytoreductive therapy. The median follow-up was 9 years (range 7-11 years). One patient transformed to myelofibrosis and 2 patients developed acute myeloid leukemia. Thrombotic complications included stroke in 7 patients, retinal vein and mesenteric vein thrombosis in 1 patient each. Bleeding occurred in 1 patient. Eleven patients died (40%) and death was likely related to underlying PV in 4 patients. Of 40 idiopathic polycythemia patients, 30 were males and 10 females. The median age at diagnosis was 59 years (range 30-84 years). Patients with idiopathic polycythemia were treated with phlebotomy to a target hematocrit<0.50 (36 patients) or hydroxycarbamide (3 patients). The median follow-up was 6 years (2-11 years). One patient developed acute myeloid leukemia after 8 years of hydroxycarbamide therapy. Thrombosis was observed in 15 patients: stroke in 5 patients, acute coronary syndrome in 6 patients and venous thrombosis in 4 patients. Red cell indices returned to normal without any interventions in 25 patients over a median duration of 5 years (range 2-8 years). Seven patients died and death was related either to polycythemia or hydroxycarbamide in 1 patient.

Conclusion
Disease progression occurred in 11% (3/27) and thrombosis in 33% (9/27) of patients with PV. Idiopathic polycythemia was associated with thrombosis in 37% (15/40) of patients. Our findings indicate that thrombosis occurs with equal or higher frequency in idiopathic group when compared to PV group. These patients require a stricter target hematocrit control to <0.45. However, in the absence of red cell mass studies to confirm the presence of true erythrocytosis, it is unclear as to who will benefit from this approach. This lack of clarity is reflected in our finding that 62% eventually normalised their red cell indices without any interventions, indicating that at least a proportion of these patients had apparent polycythemia.

Disclosures:
Chacko: Amgen : Membership on an entity’s Board of Directors or advisory committees; GSK: Membership on an entity’s Board of Directors or advisory committees. Killick:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees.