Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk‐stratification and management

Abstract

Disease Overview: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms respectively characterized by erythrocytosis and thrombocytosis; other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus, and risk of leukemic or fibrotic transformation. Diagnosis: Bone marrow morphology remains the cornerstone of diagnosis. In addition, the presence of JAK2 mutation is expected in PV while approximately 90% of patients with ET express mutually exclusive JAK2, CALR, or myeloproliferative leukemia mutations. In ET, it is most important to exclude the possibility of prefibrotic myelofibrosis. Survival: Median survivals are 14 years for PV and 20 years for ET; the corresponding values for younger patients are 24 and 33 years. Certain mutations (mostly spliceosome) and abnormal karyotype might compromise survival in PV and ET. Life‐expectancy in ET is inferior to the control population. Driver mutations have not been shown to affect survival in ET. Risk of thrombosis is higher in JAK2‐mutated ET. Leukemic transformation rates at 10 years are estimated at <1% for ET and 3% for PV. Thrombosis Risk: In PV, 2 risk categories are considered: high (age > 60 years or thrombosis history present) and low (absence of both risk factors); in ET, 4 risk categories are considered: very low (age ≤ 60 years, no thrombosis history, JAK2 wild‐type), low (same as very low but JAK2 mutation present), intermediate (age > 60 years, no thrombosis history, JAK2 wild‐type) and high (thrombosis history present or age > 60 years with JAK2 mutation). Risk‐Adapted Therapy: The main goal of therapy in both PV and ET is to prevent thrombohemorrhagic complications. All patients with PV require phlebotomy to keep hematocrit below 45% and once‐ or twice‐daily aspirin (81 mg), in the absence of contraindications. Very low‐risk ET might not require therapy while aspirin therapy is advised for low‐risk disease. Cytoreductive therapy is recommended for high‐risk ET and PV but it is not mandatory for intermediate‐risk ET. First‐line drug of choice for cytoreductive therapy, in both ET and PV, is hydroxyurea and second‐line drugs of choice are interferon‐α and busulfan. We do not recommend treatment with ruxolutinib in PV, unless in the presence of severe and protracted pruritus or marked splenomegaly that is not responding to the aforementioned drugs.

Efficacy and safety of anagrelide as a first‐line drug in cytoreductive treatment‐naïve essential thrombocythemia patients in a real‐world setting

“…Hydroxyurea is widely used in cytoreduction therapy for ET patients and its efficacy has been demonstrated. 7 Our study found that the use of anagrelide as a first-line therapy for Japanese ET patients showed good thrombocytopenic effects and demonstrated a safety profile consistent with that of previous studies. 8,9,13,22,24 THEs are closely related to driver gene mutations, 16,32 non-driver mutations, 33 WBC count, 28 neutrophil rate, 34 and other thrombotic risks, in addition to treatment choices.…”

“…However, because of the results of a primary thrombocythemia-1 (PT-1) trial published in 2005, 6 anagrelide remains classified as a second-line therapy in Europe, 2 and it is classified as less than second-line therapy in the United States. 7 Based on the results of the ANAHYDRET Study, which showed the non-inferiority of anagrelide to hydroxyurea, 8 as well as the results of a phase III clinical trial in Japanese patients (published in 2013), 9 anagrelide was approved in Japan as a first-line therapy for ET patients in 2014. In Europe, there have been concerns regarding a risk of leukemogenesis, based on the results of a largescale joint observational study conducted in 13 European countries (Evaluation of Anagrelide Efficacy and Long-term Safety [EXELS] Study [10][11][12][13] ; thus, anagrelide is mainly used in young ET patients, which has led to a gap in therapeutic agents between European countries and the United States.…”

Thrombosis among 1537 patients with JAK2V617F‐mutated myeloproliferative neoplasms: Risk factors and development of a predictive model

“…We further refined the analysis of thrombosis in patients with JAK2 V617F -mutated MPN with different subtypes, and the results show that the risk of thrombosis in PV patients was significantly higher than that in ET and PMF patients. For PV patients, similar to the study by Tefferi A et al, 25 age ≥60 years, history of thrombosis and V617F% ≥50% were risk factors affecting PV thrombosis, especially arterial thrombosis. In PV patients, the incidence of thrombosis in patients with V617F% ≥50% was 4.632 times higher than that in patients with V617F% <50%.…”

Laparoscopic hepatectomy in a patient with uncontrolled polycythaemia vera

“…It should be suspected in any patient with an elevated haemoglobin or haematocrit and oxygen saturation above 92% on air. Diagnosis is made using the World Health Organization criteria . Causes of a secondary erythrocytosis should be excluded.…”

“…Up to 46% of patients with polycythaemia vera, and nearly 80% with uncontrolled disease, suffer one of these complications or death during the peri‐operative period . Pre‐operative optimisation of these patients includes therapeutic phlebotomy, management of cardiovascular risk factors, acetylsalicylic acid and cytoreductive therapies .…”