Essential thrombocythemia: 2024 update on diagnosis, risk stratification, and management

Abstract

OverviewEssential thrombocythemia is a Janus kinase 2 (JAK2) mutation‐prevalent myeloproliferative neoplasm characterized by clonal thrombocytosis; clinical course is often indolent but might be interrupted by thrombotic or hemorrhagic complications, microcirculatory symptoms (e.g., headaches, lightheadedness, and acral paresthesias), and, less frequently, by disease transformation into myelofibrosis (MF) or acute myeloid leukemia.DiagnosisIn addition to thrombocytosis (platelets ≥450 × 109/L), formal diagnosis requires the exclusion of other myeloid neoplasms, including prefibrotic MF, polycythemia vera, chronic myeloid leukemia, and myelodysplastic syndromes with ring sideroblasts and thrombocytosis. Bone marrow morphology typically shows increased number of mature‐appearing megakaryocytes distributed in loose clusters.Genetics: Approximately 80% of patients express myeloproliferative neoplasm driver mutations (JAK2, CALR, MPL), in a mutually exclusive manner; in addition, about 50% harbor other mutations, the most frequent being TET2 (9%–11%), ASXL1 (7%–20%), DNMT3A (7%), and SF3B1 (5%). Abnormal karyotype is seen in <10% of patients and includes +9/20q−/13q‐.Survival and PrognosisLife expectancy is less than that of the control population. Median survival is approximately 18 years but exceeds >35 years in younger patients. The triple A survival risk model, based on Age, Absolute neutrophil count, and Absolute lymphocyte count, effectively delineates high‐, intermediate‐1‐, intermediate‐2‐, and low‐risk disease with corresponding median survivals of 8, 14, 21, and 47 years.Risk Factors for ThrombosisFour 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 (same as low but age >60 years), and high (thrombosis history or age >60 years with JAK2 mutation).Mutations and PrognosisMPL and CALR‐1 mutations have been associated with increased risk of MF transformation; spliceosome with inferior overall and MF‐free survival; TP53 with leukemic transformation, and JAK2V617F with thrombosis. Leukemic transformation rate at 10 years is <1% but might be higher in JAK2‐mutated patients with extreme thrombocytosis and those with abnormal karyotype.TreatmentThe main goal of therapy is to prevent thrombosis. In this regard, once‐daily low‐dose aspirin is advised for all patients and twice daily for low‐risk disease. Cytoreductive therapy is advised for high‐risk and optional for intermediate‐risk disease. First‐line cytoreductive drugs of choice are hydroxyurea and pegylated interferon‐α and second‐line busulfan.Additional ContentThe current review includes specific treatment strategies in the context of extreme thrombocytosis, pregnancy, splanchnic vein thrombosis, perioperative care, and post‐essential thrombocythemia MF, as well as new investigational drugs.

Association of the systemic immune-inflammation index with anemia: a population-based study

“…Sensitivity analyses were performed by excluding participants with high or low platelet counts (<100 or >450×10 3 cells/ml). The exclusion criteria for our study refer to two references related to thrombocytopenia (16) and thrombocytosis (17).…”

Momelotinib – a promising advancement in the management of myelofibrosis in adults with anemia

“…Other high risk molecular mutations, including ASXL1, SRSF2 , U2AF1 , and EZH2 are associated with inferior survival ( 10 ). Mutations such as IDH1/IDH2, TP53, DNMT3A , and LNK are more frequent in blast phase MPN ( 11 ). The pathogenetic role of these mutations involves disruption of epigenetic, RNA splicing, or transcriptional regulation.…”

“…The stromal changes in MF, particularly intense in MF compared to PV and ET, involve abnormal proliferation of fibroblasts, endothelial, and mesenchymal cells. The role of fibroblasts in bone marrow fibrosis is supported by their resemblance to hematopoietic stem cells and monocytes ( 11 ).…”

“…AEs leading to discontinuation of the study drugs occurred in 13.1% of patients taking MMB and 5.6% of patients taking ruxolitinib. Additionally, AEs resulting in dose reduction or temporary interruption of the study drugs were reported by 17.8% of patients receiving MMB and 36.6% of patients receiving Ruxolitinib ( 11 ).…”

The triple A model (age, absolute neutrophil count, absolute lymphocyte count‐AAA) predicts survival and thrombosis in polycythemia vera

“…1 Advanced age, leukocytosis, abnormal karyotype, and adverse mutations are associated with inferior overall survival (OS) in PV, 2 while leukocytosis and prior thrombosis are the main determinants of OS in ET patients. 3 In recent years, significant efforts have been made in order to refine the current risk stratification in MPNs. A major breakthrough has been the development of the molecularly defined risk stratification in PV and ET (MIPSS-PV and MIPSS-ET) 4 ; however, molecular analyses are costly, require specialized infrastructure, and are not widely available.…”