Long‐term follow‐up of essential thrombocythemia patients treated with anagrelide: subgroup analysis according to <scp>JAK</scp>2/<scp>CALR</scp>/<scp>MPL</scp> mutational status

Osorio, María José Mela; Ferrari, Luciana; Goette, Nora Paula; Gutiérrez, Marina; Glembotsky, Ana Claudia; Maldonado, Ana Carolina; Lev, Paola Roxana; Álvarez, Catalina; Korin, Laura; Marta, Rosana Fernanda; Molinas, Felisa C.; Heller, Paula G.

doi:10.1111/ejh.12614

Cited by 18 publications

(10 citation statements)

References 32 publications

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“…The findings of increased WBC count, neutrophil rate, and Hb level in the JAK2-ET group in our cohort, compared with the CALR-ET group, are consistent with previously reported findings. 30,31 In addition, the lack of a significant difference in platelet count between the two groups might be due to the small sample size of our cohort. There was no significant difference in the median daily dose F I G U R E 2 Median platelet count before and after treatment in each of the three groups.…”

Section: Discussionmentioning

confidence: 92%

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

Ito

Hashimoto

Tanaka

et al. 2019

European J of Haematology

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Objective: This study aimed to retrospectively assess the efficacy and safety of anagrelide in cytoreduction therapy-naïve essential thrombocythemia (ET) patients in a real-world setting.Method: Data from 53 ET patients who received anagrelide as a first-line therapy were reviewed for patient characteristics, antiplatelet status, cytoreduction status, therapeutic effects, adverse events, thrombohemorrhagic event development, progression to myelofibrosis or acute leukemia, and cause of death. Results:The rate of achieving a platelet count of <600 × 10 9 /L during anagrelide monotherapy was 83.0%. Adverse events occurred in 32 of 53 patients, and tended to be slightly more severe in patients with cardiac failure; however, they were mostly tolerable. The therapeutic effect of anagrelide was consistent, regardless of genetic mutation profiles. The incidence of anemia as an adverse event was significantly higher in the CALR mutation-positive group. Favorable platelet counts were also achieved in patients for whom hydroxyurea was introduced as a replacement for anagrelide or in addition to anagrelide because of unresponsiveness or intolerance to treatment. Conclusion:In Japanese cytoreduction therapy-naïve ET patients, anagrelide administration as a first-line therapy demonstrated favorable effects in reducing platelet counts, and its safety profile that was generally consistent with those in previous reports. K E Y W O R D S anagrelide, essential thrombocythemia, first-line, treatment | 117 ITO eT al. Complete response, n (%) 27 (50.9) Partial response, n (%) 18 (34.0) No response, n (%) 8 (15.1) AEs (≥5% of patients) Palpitations, n (%) 14 (26.4) Headache, n (%) 11 (20.8) Anemia, n (%) 10 (18.9) Diarrhea, n (%) 4 (7.5) Cardiac failure, n (%) 3 (5.7) AEs (grade 3) Anemia, n (%) 2 (3.8) Cardiac failure, n (%) 2 (3.8) Abbreviations: AE: adverse event; SD: standard deviation.

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Section: Discussionmentioning

confidence: 92%

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

Ito

Hashimoto

Tanaka

et al. 2019

European J of Haematology

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“…In the latter study, patients receiving anagrelide experienced higher incidences of arterial thrombosis, bleeding complications, and fibrotic progression. Similarly, non-controlled studies have suggested that more than a quarter of patients receiving anagrelide therapy become anemic while a lesser percentage experience renal insufficiency and cardiac complications including arrhythmia and cardiomyopathy 46 – 50 . Therefore, we currently consider anagrelide therapy only after failure of all other drug options, including hydroxyurea, IFN-α, and busulfan.…”

Section: Risk-adapted Treatment Algorithm In Essential Thrombocythemimentioning

confidence: 99%

Essential thrombocythemia treatment algorithm 2018

Tefferi

Vannucchi

Barbui

2018

Blood Cancer Journal

103

102

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Current drug therapy for myeloproliferative neoplasms, including essential thrombocythemia (ET) and polycythemia vera (PV), is neither curative nor has it been shown to prolong survival. Fortunately, prognosis in ET and PV is relatively good, with median survivals in younger patients estimated at 33 and 24 years, respectively. Therefore, when it comes to treatment in ET or PV, less is more and one should avoid exposing patients to new drugs that have not been shown to be disease-modifying, and whose long-term consequences are suspect (e.g., ruxolitinib). Furthermore, the main indication for treatment in ET and PV is to prevent thrombosis and, in that regard, none of the newer drugs have been shown to be superior to the time-tested older drugs (e.g., hydroxyurea). We currently consider three major risk factors for thrombosis (history of thrombosis, JAK2/MPL mutations, and advanced age), in order to group ET patients into four risk categories: “very low risk” (absence of all three risk factors); “low risk” (presence of JAK2/MPL mutations); “intermediate-risk” (presence of advanced age); and “high-risk” (presence of thrombosis history or presence of both JAK2/MPL mutations and advanced age). Herein, we provide a point-of-care treatment algorithm that is risk-adapted and based on evidence and decades of experience.

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“… † Screening for JAK2 V617F, CALR and MPL mutations was perfomed as described525354. CALR and exon 10 MPL mutations were studied in JAK2 V617F-negative patients.…”

Section: Figurementioning

confidence: 99%

Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms

Oyarzún

Carestia

Lev

et al. 2016

Sci Rep

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The mechanisms underlying increased thrombotic risk in chronic myeloproliferative neoplasms (MPN) are incompletely understood. We assessed whether neutrophil extracellular traps (NETs), which promote thrombosis, contribute to the procoagulant state in essential thrombocythemia, polycythemia vera and myelofibrosis (MF) patients. Although MPN neutrophils showed increased basal reactive oxygen species (ROS), enhanced NETosis by unstimulated neutrophils was an infrequent finding, whereas PMA-triggered NETosis was impaired, particularly in MF, due to decreased PMA-triggered ROS production. Elevated circulating nucleosomes were a prominent finding and were higher in patients with advanced disease, which may have potential prognostic implication. Histone-MPO complexes, proposed as specific NET biomarker, were seldomly detected, suggesting NETs may not be the main source of nucleosomes in most patients, whereas their correlation with high LDH points to increased cell turn-over as a plausible origin. Lack of association of nucleosomes or NETs with thrombosis or activation markers does not support their use as predictors of thrombosis although prospective studies in a larger cohort may help define their potential contribution to MPN thrombosis. These results do not provide evidence for relevant in vivo NETosis in MPN patients under steady state conditions, although availability of standardized NET biomarkers may contribute to further research in this field.

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Long‐term follow‐up of essential thrombocythemia patients treated with anagrelide: subgroup analysis according to JAK2/CALR/MPL mutational status

Abstract: Although CALR(+) patients were at higher risk of developing anemia, anagrelide proved effective among all molecular subsets, indicating that mutational status does not seem to represent a major determinant of choice of cytoreductive treatment among essential thrombocythemia therapies.

Cited by 18 publications

References 32 publications

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

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

Essential thrombocythemia treatment algorithm 2018

Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms

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