دانلود رایگان مقاله انگلیسی الگوریتم درمان پلی سایتمی حقیقی - NCBI 2018

Abstract

Recently reported mature survival data have confirmed the favorable prognosis in polycythemia vera (PV), with an estimated median survival of 24 years, in patients younger than age 60 years old. Currently available drugs for PV have not been shown to prolong survival or alter the natural history of the disease and are instead indicated primarily for prevention of thrombosis. Unfortunately, study endpoints that are being utilized in currently ongoing clinical trials in PV do not necessarily target clinically or biologically relevant outcomes, such as thrombosis, survival, or morphologic remission, and are instead focused on components of disease palliation. Even more discouraging has been the lack of critical appraisal from “opinion leaders”, on the added value of newly approved drugs. Keeping these issues in mind, at present, we continue to advocate conservative management in low-risk PV (phlebotomy combined with once- or twice-daily aspirin therapy) and include cytoreductive therapy in “high-risk” patients; in the latter regard, our first, second, and third line drugs of choice are hydroxyurea, pegylated interferon-α and busulfan, respectively. In addition, it is reasonable to consider JAK2 inhibitor therapy, in the presence of protracted pruritus or markedly enlarged splenomegaly shown to be refractory to the aforementioned drugs.

Conclusions

Patients with PV should look forward to long and productive life and avoid exposure to new drugs whose long-term consequences are not known and might include acceleration of clonal degeneration into acute myeloid leukemia or myelofibrosis. This is not only of theoretical concern and has happened before to PV patients treated with chlorambucil, radiophosphorus or pipobroman37,39 and to ET patients treated with anagrelide76. Decades of experience with hydroxyurea and busulfan, for the treatment of PV or ET, has not produced controlled evidence that implicates either one of these two drugs as being leukemogenic or immunosuppressive. Our concern lies with the newer drugs, including IFN-α77 and ruxolutinib78,79, neither of which has been shown to be superior or safer than conventional therapy, in a controlled study with clinically relevant endpoints (e.g., survival, thrombosis or bone marrow morphologic remission). Furthermore, neither IFN-α nor ruxolutinib induces morphologic or cytogenetic remission in PV or has been shown to alter the natural history of the disease; of note, the clinical relevance of IFN-α-induced suppression of JAK2V617F allele burden, which is seen in a small minority of patients47, and also documented with busulfan therapy51, is unclear. Therefore, it is incumbent upon the MPN community of physicians and scientists to dig deeper into more precise pathogenetic mechanisms and identify targetable disease-specific pathways. In other words, our patients need drugs with anti-tumor activity and do not have to settle for symptomatic relief.