Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN.
Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy.
Mayo Clin Proc. 2015 Sep;90(9):1283-93. doi: 10.1016/j.mayocp.2015.05.014.
Bone marrow (BM) morphologic features remain the cornerstone of diagnosis in both essential thrombocythemia (ET) and polycythemia vera (PV). In addition, recently discovered mutations, such as JAK2, CALR, and MPL, have proven useful in facilitating the diagnostic process. A JAK2 mutation is expected in PV, and its absence makes the diagnosis unlikely. However, JAK2 mutations also occur in about 60% of patients with ET, which underlines the need for BM examination in distinguishing JAK2-mutated ET from PV when the hemoglobin/hematocrit level is diagnostically equivocal (ie, as in "masked" PV). Most patients with JAK2-unmutated ET express CALR or MPL mutations, with respective estimated incidences of 22% and 3%, while approxmately 15% are wild-type for all 3 mutations (ie, they are triple-negative). As such, CALR first, followed by MPL if CALR is absent, mutation screening is appropriate in the diagnostic work-up of JAK2-unmutated ET but does not replace the need for BM morphologic examination in (1) confirming the diagnosis in triple-negative ET and (2) distinguishing ET from other myeloproliferative neoplasms that share the same mutations, including masked PV and early/prefibrotic myelofibrosis. Young patients (aged < 60 years) with ET or PV and no history of thrombosis are conventionally regarded as having "low-risk" disease. First-line treatment in low-risk PV is phlebotomy to achieve a hematocrit target of 45% and low-dose aspirin, and first-line treatment in ET is observation alone in the absence of additional risk factors for arterial thrombosis (ie, JAK2 mutation and cardiovascular risk factors) or low-dose aspirin therapy, once or twice daily, in the presence of one or both of these risk factors, respectively. Cytoreductive therapy is indicated in high-risk (patients aged ≥ 60 years or a history of thrombosis) PV or ET in the form of hydroxyurea as first-line and interferon alfa or busulfan as second-line drugs of choice. We do not use ruxolitinib in patients with PV unless they have severe pruritus or symptomatic splenomegaly that is proved to be refractory to hydroxyurea, interferon alfa, and busulfan.
骨髓（BM）形态学特征仍然是原发性血小板增多症（ET）和真性红细胞增多症（PV）诊断的基石。此外，最近发现的突变，如 JAK2、CALR 和 MPL，已被证明有助于诊断过程。PV 中预计会出现 JAK2 突变，其缺失使诊断不太可能。然而，JAK2 突变也发生在约 60%的 ET 患者中，这强调了在血红蛋白/血细胞比容水平诊断不确定时（即“隐匿性”PV），需要进行 BM 检查以区分 JAK2 突变的 ET 和 PV。大多数 JAK2 未突变的 ET 患者表达 CALR 或 MPL 突变，分别估计发生率为 22%和 3%，而约 15%的患者所有 3 种突变均为野生型（即三阴性）。因此，在 JAK2 未突变的 ET 诊断中，CALR 首先进行突变筛查，其次是 CALR 缺失时的 MPL，如果需要，仍需要进行 BM 形态学检查，以确认（1）三阴性 ET 的诊断，（2）区分 ET 与具有相同突变的其他骨髓增殖性肿瘤，包括隐匿性 PV 和早期/纤维化前期骨髓纤维化。年龄<60 岁的 ET 或 PV 且无血栓史的年轻患者通常被认为患有“低危”疾病。低危 PV 的一线治疗是放血以达到 45%的血细胞比容目标和低剂量阿司匹林，ET 的一线治疗是在无动脉血栓形成的其他危险因素（即 JAK2 突变和心血管危险因素）或低剂量阿司匹林治疗的情况下单独观察，分别存在一个或两个这些危险因素时，每天一次或两次。高危（年龄≥60 岁或有血栓史）PV 或 ET 采用羟基脲作为一线治疗，干扰素α或白消安作为二线药物。除非患者有严重瘙痒或症状性脾肿大且证明对羟基脲、干扰素α和白消安耐药，否则我们不在 PV 患者中使用鲁索替尼。
