An agenda for future research projects in polycythemia vera and essential thrombocythemia

Barbui, Tiziano; Vannucchi, Alessandro M.; Guglielmelli, Paola; Stefano, Valerio De

doi:10.3324/haematol.2019.246207

Cited by 6 publications

(6 citation statements)

References 47 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Finally, the possibility that the current model merely selects morphologically bypassed pre‐fibrotic MF cases or, in other words, the fact that VAF of JAK2 V617F may help, together with clinical and histopathological picture, in discriminating true ET from pre‐MF cases is an intriguing issue that might be studied in large cohorts of patients with a centralized histopathological review by a panel of experts 24 . However, from a practical standpoint, this possibility by itself does not undermine the main objective of the current study, which is to identify patients who require close monitoring and appropriate counseling.…”

Section: Discussionmentioning

confidence: 99%

Clinical and molecular predictors of fibrotic progression in essential thrombocythemia: A multicenter study involving 1607 patients

et al. 2021

Self Cite

View full text Add to dashboard Cite

The current retrospective study involving a total of 1607 patients was designed to identify clinical and molecular variables that were predictive of inferior myelofibrosis‐free survival (MFS) in WHO‐defined essential thrombocythemia (ET), utilizing three independent patient cohorts: University of Florence, Italy (n = 718); Mayo Clinic, USA (n = 479) and Policlinico Gemelli, Catholic University, Rome, Italy (n = 410). The Florence patient cohort was first examined to identify independent risk factors for MFS, which included age > 60 years (HR 2.5, 95% CI 1.3–4.9), male sex (2.1, 1.2–3.9), palpable splenomegaly (2.1, 1.2–3.9), CALR 1/1‐like or MPL mutation (3.4, 1.9–6.1) and JAK2V617F variant allele frequency > 35% (4.2, 1.6–10.8). Subsequently, an operational molecular risk category was developed and validated in the other two cohorts from Mayo Clinic and Rome: “high molecular risk” category included patients with JAK2V617F VAF >35%, CALR type 1/1‐like or MPL mutations; all other driver mutation profiles were assigned to “low molecular risk” category. The former, compared to the latter molecular risk category, displayed significantly higher risk of fibrotic transformation: Florence cohort with respective fibrotic transformation risk rates of 8% vs. 1.2% at 10 years and 33% vs. 8% at 20 years (p < 0.001; HR 6.1; 95% CI 3.2–11.7); Mayo Cohort, 16% vs. 7% at 10 years and 44% vs. 25% at 20 years (p < 0.001; HR 2.5; 95% CI 1.6–4.1); and Rome cohort 7.8% vs. 4.6% at 10 years and 31.2% vs. 7.1% at 20 years (p = 0.007, HR 2.7; 95% CI 1.3–5.8). The present study provides practically useful risk signals for fibrotic transformation in ET and facilitates identification of patients who require close monitoring and appropriate counseling.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical and molecular predictors of fibrotic progression in essential thrombocythemia: A multicenter study involving 1607 patients

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The same can be said about low‐risk ET, in general, while an argument can be made for innovative clinical trials to target ET patients with increased ANC or abnormal karyotype. Furthermore, controlled studies in ET should aspire to use primary endpoints that reflect meaningful health outcomes, such as thrombosis and progression‐free or overall survival, rather than parameters of dubious clinical relevance, such as platelet count 96,166 …”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, controlled studies in ET should aspire to use primary endpoints that reflect meaningful health outcomes, such as thrombosis and progression-free or overall survival, rather than parameters of dubious clinical relevance, such as platelet count. 96,166…”

Section: Discussionmentioning

confidence: 99%

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

Tefferi,

Vannucchi,

Barbui

2024

American J Hematol

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…An increased incidence of thrombotic events has been reported in patients over 60 years of age and/or in those with leukocytosis and thrombocytosis. 8,9,10 JAK2 mutations have been associated with an increased risk of thrombosis, and JAK2 homozygous status was found to increase the risk of vascular complications 11,12 .…”

Section: Introductionmentioning

confidence: 99%

The evaluation of patients with essential thrombocythemia in terms of risk of thrombosis

Sunu

Güneş

Akat

et al. 2021

Rev. Assoc. Med. Bras.

View full text Add to dashboard Cite

OBJECTIVE:The aim of this study was to compare the incidence of factors associated with an increased risk of thrombosis in patients with essential thrombocythemia.METHODS: A total of 200 patients followed-up in our unit with a diagnosis of essential thrombocythemia in 13 years were analyzed retrospectively.RESULTS: Of the study participants, 60.5% were females and 39.5% were males, with an overall mean (±SD) age of 54.93 (±14.21) years. In 119 patients, Janus Kinase 2 was positive with 56.3% of cases. When two patient categories were defined as those with or without history of thrombosis, no significant differences were found in terms of Janus Kinase 2 positivity, mean age, as well as white blood cells and platelet counts (p>0.05). Also, no significant differences in thrombotic event incidence were found between patient categories defined on the basis of cut-off values for white blood cells (cut-off values of 15×10 3 /mm 3 and 8.7×10 3 /mm 3 ) and platelets (cut-off values of 1500×10 3 /mm 3 ) (p>0.05).CONCLUSION: Although our results are generally in line with the published data, some divergence from previous results has been observed with respect to risk factors for thrombotic events. Absence of a correlation between leukocytosis and thrombosis may be related with the significant decline in white blood cells after treatment. Also, a significant reduction in platelet counts occurring in association with treatment is linked with a lowered incidence of thrombosis. Janus Kinase 2-positive patients had a similar thrombosis frequency with that reported in the literature.

show abstract

An agenda for future research projects in polycythemia vera and essential thrombocythemia

Cited by 6 publications

References 47 publications

Clinical and molecular predictors of fibrotic progression in essential thrombocythemia: A multicenter study involving 1607 patients

Clinical and molecular predictors of fibrotic progression in essential thrombocythemia: A multicenter study involving 1607 patients

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

The evaluation of patients with essential thrombocythemia in terms of risk of thrombosis

Contact Info

Product

Resources

About