关于原发性血小板血症治疗的建议依赖于在发现CALR突变之前进行的研究。2020年5月20日,欧洲白血病网络年会举行,目的是确定骨髓增生性肿瘤中未满足的临床需求。因为具有CALR突变的患者具有特定的临床特征,欧洲白血病网认为CALR突变的原发性血小板血症的治疗是未满足的临床需求。提出了根据当前证据制定带有建议的共识文件,作为解决CALR突变的原发性血小板血症治疗不确定性的解决方案。随后成立了一个由四名欧洲白血病网络成员组成的指导委员会,并招募了一个由该领域的十名专家组成的小组。专家们在CALR突变的原发性血小板血症的治疗中提出了51种潜在的未满足的临床需求,并要求对每个主题的相关性进行评分。确定了作为相关未满足的临床需求获得最高分的主题,包括低风险患者的抗血小板治疗,极端血小板增多症的定义及其在低风险患者中的管理,细胞减少的适应症和治疗目标,年轻患者(<60岁)的首选一线治疗,和怀孕的管理。指导委员会修改了每个主题的现有证据后,通过使用基于电子邮件的管理和改进知识的建议达成共识,两轮,Delphi方法。当90%的小组成员同意一项声明并包括14项建议和6项解决方案建议时,达成了共识。主要建议包括仔细观察无症状的经典患者,低风险,CALR突变的原发性血小板血症,无心血管危险因素;对于血小板计数为每升1000-1500×109血小板的低风险症状患者,应谨慎使用抗血小板治疗,在这种情况下,细胞减少是一个适当的选择,特别是如果有明确的VonWillebrand病;对于严重的血小板增多症(血小板计数>1500×109血小板/L),建议细胞减量,对于年轻患者,聚乙二醇干扰素α是首选方案;对于不符合聚乙二醇干扰素α治疗条件的患者,可同时给予羟基脲和阿那格雷;对于高危妊娠患者的治疗方案不应根据基因型而改变.欧洲白血病网建议在CALR突变的原发性血小板血症患者的常规治疗中使用这些建议。在这一领域设计新的临床研究可能是有用的。
Recommendations regarding management of essential thrombocythaemia rely on studies done before the discovery of the CALR mutation. On May 20, 2020, the European LeukemiaNet annual meeting was held with the goal to identify unmet clinical needs in myeloproliferative neoplasms. Because patients with a CALR mutation have specific clinical characteristics, treatment of CALR-mutated essential thrombocythaemia was considered an unmet clinical need by the European LeukemiaNet. The elaboration of a
consensus document with recommendations according to current evidence was proposed as a solution for resolving uncertainties in the treatment of CALR-mutated essential thrombocythaemia. A steering committee comprising four European LeukemiaNet members was then formed and a panel of ten experts in the field was recruited. The experts proposed 51 potential unmet clinical needs in the management of CALR-mutated essential thrombocythaemia and were asked to score the relevance of each topic. Those topics that obtained the highest scores as relevant unmet clinical needs were identified, including antiplatelet therapy in patients at low risk, definition of extreme thrombocytosis and its management in patients at low risk, indications of cytoreduction and targets of therapy, first-line treatment of choice in young patients (<60 years), and management of pregnancy. After the steering committee revised the available evidence for each topic, a
consensus on management and proposal for improving knowledge was achieved by use of an email-based, two round, Delphi approach.
Consensus was achieved when 90% of the panellists agreed with a statement and included 14 recommendations and six solution proposals. Key recommendations included careful observation for asymptomatic patients with classical, low-risk, CALR-mutated essential thrombocythaemia without cardiovascular risk factors; caution in the use of antiplatelet therapy for symptomatic patients at low risk with platelet counts of 1000-1500 × 109 platelets per L, in such cases cytoreduction is an adequate option, especially if adquired Von Willebrand disease is present; cytoreduction is recommended for extreme thrombocytosis (platelet count >1500 × 109 platelets per L) with pegylated interferon alfa being the preferred option for younger patients; both hydroxycarbamide and anagrelide might be given to patients ineligible for pegylated interferon alfa; and treatment algorithms for patients with high-risk pregnancies should not be changed according to genotype. The European LeukemiaNet proposes to use these recommendations in the routine management of patients with CALR-mutated essential thrombocythaemia, and designing new clinical studies in this field might be useful.