Interferon α-2b gains high sustained response therapy for advanced essential thrombocythemia and polycythemia vera with JAK2V617F positive mutation
Introduction
Chronic myeloproliferative disorders (MPDs) constitute one of five categories of myeloid malignancies, according to the World Health Organization (WHO) classification system for hematopoietic tumors [1]. Essential thrombocythemia (ET) and polycythemia vera (PV) are sub-categories of MPDs [2]. For a long time, the absence of specific genetic or molecular markers caused problems in the differential diagnosis in MPDs. Recently, the acquired gain-of-function V617F mutation in the Janus Kinase 2 (JAK2V617F) has been found to be the major mutation involved in BCR/ABL negative classical MPDs. It is present in the mutational frequency of 96% in PV, 55% of ET patients [3], [4].
The risk of thrombosis, in both ET and PV, exceeds 20% and a substantial proportion of patients experience vasomotor disturbances [5]. Risk factors for shortened survival in both ET and PV include history of thrombosis, leukocytosis, advanced age and anemia. Accordingly, the goal of current therapy in PV and ET is primarily to prevent thrombohemorrhagic complications.
The related treatment for patients with ET and PV should aim at avoiding thromboembolic complications by bone marrow-suppressive therapy. Such treatments ideally should not increase the risk of acute leukemia [6]. Hydroxyurea (HU) generally is considered the treatment of choice for MPDs-associated thrombocythemia [7] and recently showed superior activity over anagrelide. On the other hand, the clinical effectiveness of interferon α-2b (IFN α-2b) had been demonstrated nearly a quarter of a century ago in PV in the US, and almost simultaneously in ET patients by French and Austrian groups [8].
At present, it is still not determined whether IFN α-2b gains the therapy superiority for the PV and ET with or without positive JAK2V617F mutation. The study represents the multicenter study reviews to evaluate efficacy and adverse events of IFN α-2b for advanced ET or PV adult patients (hematocrit >45% or extreme thrombocytosis >1000 × 109/L) or thrombosis history related to JAK2V617F mutation.
Section snippets
Study population
This open-label, observational, multicenter clinical assessment enrolled participants from February 2009 to March 2014. All adult patients (ages 18–65 years old) were diagnosed according to the WHO 2008 classification and fit a composite assessment of clinical and laboratory features [9]. Enrolled advanced patients with extreme thrombocytosis risks or thrombosis history gave written informed consent before entering the study. This study was approved by the institution review board at each of
Enrolled patients with clinical characteristics
The median age of 123 patients with ET was 49 years old. Two treatment groups JAK2V617F+ versus JAK2V617F−) were well balanced in age (median: 47 versus 50 years old), WBC (median: 26 versus 22 × 109/L), hemoglobin (median: 161 versus 166 g/L), and platelet (median: 1125 versus 1127 × 109/L) counts (P > 0.05) at the time of random assignment (Table 1).
The median age of 136 PV patients with JAK2V617F+ was 47 years old. Two treatment groups (IFN α-2b versus HU) were well balanced in age (median: 47
Discussion
PV and ET are chronic MPDs characterized by clonal expansion of an abnormal hematopoietic stem/progenitor cell. Patients with MPDs have a clinical course characterized by a thrombophilic state, which results in arterial and venous thromboses that greatly impacts morbidity and mortality. For ET and PV patients with extreme thrombocytosis risks or thrombosis history, the agent of choice to manage hyperviscosity is HU or IFN. HU provides effective control of the hematocrit in approximately 80% of
Conflict of interest statement
All authors discussed the results and commented on the manuscript. I would like to declare on behalf of my co-authors that this work is original research that has not been published previously and is not under consideration for publication elsewhere, either in part of in whole. All the authors listed have approved the manuscript that is enclosed.
Acknowledgments
We would like to thank all the patients and the clinicians from the participating sites. This work was supported by grants from the Natural Science Foundation of Inner Mongolia (2013MS1157) and Inner Mongolia Autonomous Region Health and Family Planning health research projects (201302059).
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Appropriate management of polycythaemia vera with cytoreductive drug therapy: European LeukemiaNet 2021 recommendations
2022, The Lancet HaematologyCitation Excerpt :In two meta-analyses that evaluated the rate of vascular events in 1457 patients with polycythaemia vera treated with either pegylated or non-pegylated interferon alfa, the results indicated a very low rate of thrombosis of 0·2–0·4 events per 100 patient years.36,38 In summary, high-quality evidence (table 2)2,15,26,36–38,53–56 supports the use of interferon alfa rather than hydroxyurea to attain haematocrit control and a molecular response, and moderate-quality evidence suggests that treatment with interferon alfa delays or reduces the risk of disease transformation into myelofibrosis and secondary malignancies compared with hydroxyurea. Therefore, the expert panel recommended either pegylated or non-pegylated interferon alfa as cytoreductive drug therapy in patients younger than 60 years with polycythaemia vera, especially because their potentially longer lifespan might be associated with a higher cumulative incidence of secondary malignancies and myelofibrosis (panel 1).
Decitabine plus thalidomide yields more sustained survival rates than decitabine monotherapy for risk-tailored elderly patients with myelodysplastic syndrome
2015, Leukemia ResearchCitation Excerpt :A total of 107 untreated elderly patients (age 60–82 years old) provided written informed consent and had received DAC (52/107) or DAC plus thalidomide (55/107) therapy for MDS based on a randomly assigned number (Fig. 1). The study was approved by the institutional review board at each of the participating centers [12,13]. All patients were stratified by IPSS scores [14]: low risk (IPSS low or intermediate-1) and high risk (IPSS intermediate-2 or high) [15].
Clinical outcomes of interferon therapy for polycythemia vera and essential thrombocythemia: a systematic review and meta-analysis
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- 1
These authors contributed equally to this work.