3023 Mayo Clinic Patients With Myeloproliferative Neoplasms: Risk-Stratified Comparison of Survival and Outcomes Data Among Disease Subgroups

Szuber, Natasha; Mudireddy, Mythri; Nicolosi, Maura; Penna, Domenico; Vallapureddy, Rangit; Lasho, Terra L.; Finke, Christy; Begna, Kebede H.; Elliott, Michelle A.; Hook, C. Christopher; Wolanskyj, Alexandra P.; Patnaik, Mrinal M.; Hanson, Curtis A.; Ketterling, Rhett P.; Sirhan, Shireen; Pardanani, Animesh; Gangat, Naseema; Busque, Lambert; Tefferi, Ayalew

doi:10.1016/j.mayocp.2018.08.022

Cited by 127 publications

(127 citation statements)

References 43 publications

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“…Median survival in young patients with PV and ET might exceed 30 years and is not that much worse for older patients. 30,31 Therefore, it is very important to avoid non-evidence based therapeutic adventures in PV or ET that might shorten life-expectancy and increase the rate of fibrotic or leukemic transformations, as has been previously reported with chlorambucil, 71 radiophosphorus, 72 pipobroman 110 and most recently with anagrelide. 82,111 To date, drug therapy has not been shown to improve survival or prevent leukemic/fibrotic transformation in either ET or PV; therefore treatment is primarily directed at preventing thrombotic complications.…”

Section: Discussionmentioning

confidence: 99%

Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk‐stratification and management

2020

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Disease overview: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPN) respectively characterized by clonal 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 MPL mutations (so called driver mutations). In ET, it is most important to exclude the possibility of prefibrotic myelofibrosis. Survival: Median survivals are approximately 15 years for PV and 18 years for ET; the corresponding values for patients age 40 or younger were 37 and 35 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 but risk of thrombosis is higher in JAK2 mutated cases. Leukemic transformation rates at 10 years are estimated at <1% for ET and 3% for PV. Thrombosis risk: In PV, two risk categories are considered: high (age > 60 years or thrombosis history present) and low (absence of both risk factors). In ET, four risk categories are considered: very low (age ≤ 60 years, no thrombosis history, JAK2 wildtype), 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-daily 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

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Section: Discussionmentioning

confidence: 99%

Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk‐stratification and management

2020

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“…Patients with PMF depict a considerably heterogeneous clinical course, with median survival ranging from over a decade to less than 2 years. 62,89,101 In clinical practice, management of post-exon 12 PV MF, post-PV/post-ET MF is the same as PMF.…”

Section: Treatment Strategiesmentioning

confidence: 99%

Myelofibrosis biology and contemporary management

Gangat

Tefferi

2020

Br J Haematol

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Myelofibrosis is an enigmatic myeloproliferative neoplasm, despite noteworthy strides in understanding its genetic underpinnings. Driver mutations involving JAK2, CALR or MPL in 90% of patients mediate constitutive JAK-STAT signaling which, in concert with epigenetic alterations (ASXL1, DNMT3A, SRSF2, EZH2, IDH1/2 mutations), play a fundamental role in disease pathogenesis. Aberrant immature megakaryocytes are a quintessential feature, exhibiting reduced GATA1 protein expression and secreting a plethora of pro-inflammatory cytokines (IL-1 ß, TGF-ß), growth factors (b-FGF, PDGF, VEGF) in addition to extra cellular matrix components (fibronectin, laminin, collagens). The ensuing disrupted interactions amongst the megakaryocytes, osteoblasts, endothelium, stromal cells and myofibroblasts within the bone marrow culminate in the development of fibrosis and osteosclerosis. Presently, prognostic assessment tools for primary myelofibrosis (PMF) are centered on genetics, with incorporation of cytogenetic and molecular information into the mutation-enhanced (MIPSS 70-plus version 2.0) and genetically-inspired (GIPSS) prognostic scoring systems. Both models illustrate substantial clinical heterogeneity in PMF and serve as the crux for riskadapted therapeutic decisions. A major challenge remains the dearth of disease-modifying drugs, whereas allogeneic transplant offers the chance of long-term remission for some patients. Our review serves to synopsise current appreciation of the pathogenesis of myelofibrosis together with emerging management strategies.

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“…ET is a disease in which neoplastic proliferation of pluripotent stem cells causes hyperplasia of megakaryocytes in the bone marrow, leading to thrombocytosis [ 1 ]. The estimated rate of occurrence of ET is 1.2-3.0 per 100,000 people per year [ 4 , 5 ]. The probability of transformation of ET to acute leukemia or myelofibrosis is 2.9%, and the prognosis is determined by thromboembolism and bleeding symptoms [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Essential Thrombocythemia in a Nonagenarian Presenting With Acute Myocardial Infarction

Tanabe¹,

Yamaguchi²,

Sato³

et al. 2020

Cureus

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Essential thrombocythemia (ET) is a chronic Philadelphia-negative myeloproliferative neoplasm (MPN) characterized by clonal thrombocytosis and an increased risk of arterial and venous thrombosis. Because ET has a low probability of progressing to acute leukemia or myelofibrosis and its prognosis is determined by thromboembolic or bleeding symptoms, the treatment of this disease is aimed at preventing vascular events. We encountered a nonagenarian patient with ET who presented with acute myocardial infarction with ST-segment elevation. In the present case, the patient was 91 years old, and antithrombotic agents were required after the placement of drug-eluting stent. Therefore, we decided not to perform cytoreductive therapy because the risk of bleeding is higher. Very elderly patients with ET are at an increased risk of thrombotic and hemorrhagic events. The risk-benefit of antithrombotic therapy should be considered individually.

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3023 Mayo Clinic Patients With Myeloproliferative Neoplasms: Risk-Stratified Comparison of Survival and Outcomes Data Among Disease Subgroups

Cited by 127 publications

References 43 publications

Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk‐stratification and management

Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk‐stratification and management

Myelofibrosis biology and contemporary management

Essential Thrombocythemia in a Nonagenarian Presenting With Acute Myocardial Infarction

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