Risk factors for arterial versus venous thrombosis in polycythemia vera: a single center experience in 587 patients.

In a recent International Working Group on Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) study, prior arterial events and hypertension were predictors of subsequent arterial thrombosis whereas prior venous events and age ≥65 years predicted venous thrombosis in polycythemia vera (PV). In the current study, we sought to validate the above findings and identify additional predictors of arterial versus venous thrombosis. At a median follow up of 109 months, thrombosis after diagnosis occurred in 128 (22%) patients; 82 (14%) arterial and 57 (10%) venous events. On multivariate analysis, prior arterial events (<0.0001), hyperlipidemia (p = 0.03), and hypertension (p = 0.02) predicted subsequent arterial events. In comparison, prior venous events (p = 0.05), leukocytosis ≥11 × 109/L (p = 0.002), and major hemorrhage (p = 0.02) were predictors of subsequent venous events. Salient associations with arterial thrombosis included age ≥ 60 years, hypertension, diabetes, hyperlipidemia and normal karyotype whereas age ≤ 60 years, females, palpable splenomegaly and history of major hemorrhage were associated with venous thrombosis. TET2 or ASXL1 mutations did not impact arterial nor venous thrombosis. In conclusion, we identify distinct associations for arterial versus venous thrombosis in PV and confirm that a prior arterial or venous thrombotic event is the most reliable predictor of subsequent events.

Prognostic impact of bone marrow fibrosis in polycythemia vera: validation of the IWG-MRT study and additional observations.

In 2012, the International Working Group for Myeloproliferative Neoplasms (MPN) Research and Treatment (IWG-MRT) reported an associations between mild bone marrow (BM) fibrosis (⩾grade 1) in polycythemia vera (PV) and a lower incidence of thrombosis during the clinical course and a higher risk of fibrotic progression. The objective in the current study of 262 patients with PV was to validate these observations and also identify other risk factors for myelofibrosis-free survival (MFFS). About 127 (48%) patients displayed ⩾grade 1 reticulin fibrosis at the time of diagnosis; presenting clinical and laboratory features were not significantly different between patients with or without BM fibrosis. In univariate analysis, BM fibrosis had no significant impact on overall, leukemia-free or thrombosis-free survival, whereas a significant association was noted for MFFS (P=0.009, hazard ratio 2.9; 95% confidence interval 1.32-6.78); other risk factors for MFFS included leukocytosis ⩾15 × 109/l, presence of palpable splenomegaly and abnormal karyotype. During multivariable analysis, leukocytosis ⩾15 × 109/l, palpable splenomegaly and ⩾grade 1 BM reticulin fibrosis remained significant. The current study validates the previously observed association between ⩾grade 1 BM reticulin fibrosis in PV and subsequent fibrotic progression, and identifies leukocytosis and palpable splenomegaly as additional risk factors for fibrotic progression; additional studies are required to clarify the impact of BM fibrosis on thrombosis and that of abnormal karyotype on MFFS.

Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors.

Polycythemia vera (PV) and essential thrombocythemia (ET) constitute two of the three BCR-ABL1-negative myeloproliferative neoplasms and are characterized by relatively long median survivals (approximately 14 and 20 years, respectively). Potentially fatal disease complications in PV and ET include disease transformation into myelofibrosis (MF) or acute myeloid leukemia (AML). The range of reported frequencies for post-PV MF were 4.9-6% at 10 years and 6-14% at 15 years and for post-ET MF were 0.8-4.9% at 10 years and 4-11% at 15 years. The corresponding figures for post-PV AML were 2.3-14.4% at 10 years and 5.5-18.7% at 15 years and for post-ET AML were 0.7-3% at 10 years and 2.1-5.3% at 15 years. Risk factors cited for post-PV MF include advanced age, leukocytosis, reticulin fibrosis, splenomegaly and JAK2V617F allele burden and for post-ET MF include advanced age, leukocytosis, anemia, reticulin fibrosis, absence of JAK2V617F, use of anagrelide and presence of ASXL1 mutation. Risk factors for post-PV AML include advanced age, leukocytosis, reticulin fibrosis, splenomegaly, abnormal karyotype, TP53 or RUNX1 mutations as well as use of pipobroman, radiophosphorus (P(32)) and busulfan and for post-ET AML include advanced age, leukocytosis, anemia, extreme thrombocytosis, thrombosis, reticulin fibrosis, TP53 or RUNX1 mutations. It is important to note that some of the aforementioned incidence figures and risk factor determinations are probably inaccurate and at times conflicting because of the retrospective nature of studies and the inadvertent labeling, in some studies, of patients with prefibrotic primary MF or 'masked' PV, as ET. Ultimately, transformation of MPN leads to poor outcomes and management remains challenging. Further understanding of the molecular events leading to disease transformation is being investigated.