Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy.
Am J Hematol. 2023 Sep;98(9):1465-1487. doi: 10.1002/ajh.27002. Epub 2023 Jun 26.
Polycythemia vera (PV) is a JAK2-mutated myeloproliferative neoplasm characterized by clonal erythrocytosis; other features include leukocytosis, thrombocytosis, splenomegaly, pruritus, constitutional symptoms, microcirculatory disturbances, and increased risk of thrombosis and progression into myelofibrosis (post-PV MF) or acute myeloid leukemia (AML).
A working diagnosis is considered in the presence of a JAK2 mutation associated with hemoglobin/hematocrit levels of >16.5 g/dL/49% in men or 16 g/dL/48% in women; morphologic confirmation by bone marrow examination is advised but not mandated.
Abnormal karyotype is seen in 15%-20% of patients with the most frequent sole abnormalities being +9 (5%), loss of chromosome Y (4%), +8 (3%), and 20q- (3%).
Over 50% of patients harbor DNA sequence variants/mutations other than JAK2, with the most frequent being TET2 (18%) and ASXL1 (15%). Prognostically adverse mutations include SRSF2, IDH2, RUNX1, and U2AF1, with a combined incidence of 5%-10%.
Median survival is ⁓15 years but exceeds 35 years for patients aged ≤40 years. Risk factors for survival include older age, leukocytosis, abnormal karyotype, and the presence of adverse mutations. Twenty-year risk for thrombosis, post-PV MF, or AML are ⁓26%, 16% and 4%, respectively.
Two risk categories are considered: high (age >60 years or thrombosis history) and low (absence of both risk factors). Additional predictors for arterial thrombosis include cardiovascular risk factors and for venous thrombosis higher absolute neutrophil count and JAK2V617F allele burden.
Current goal of therapy is to prevent thrombosis. Periodic phlebotomy, with a hematocrit target of <45%, combined with once- or twice-daily aspirin (81 mg) therapy, absent contraindications, is the backbone of treatment in all patients, regardless of risk category. Cytoreductive therapy is reserved for high-risk disease with first-line drugs of choice being hydroxyurea and pegylated interferon-α and second-line busulfan and ruxolitinib. In addition, systemic anticoagulation is advised in patients with venous thrombosis history.
At the present time, we do not consider a drug-induced reduction in JAK2V617F allele burden, which is often incomplete and seen not only with peg-IFN but also with ruxolitinib and busulfan, as an indicator of disease-modifying activity, unless accompanied by cytogenetic and independently-verified morphologic remission. Accordingly, we do not use the specific parameter to influence treatment choices. The current review also includes specific treatment strategies in the context of pregnancy, splanchnic vein thrombosis, pruritus, perioperative care, and post-PV MF.
真性红细胞增多症（PV）是一种 JAK2 突变的骨髓增殖性肿瘤，其特征为克隆性红细胞增多；其他特征包括白细胞增多、血小板增多、脾肿大、瘙痒、全身症状、微血管紊乱以及血栓形成风险增加，并进展为骨髓纤维化（PV 后 MF）或急性髓系白血病（AML）。
如果存在 JAK2 突变，且男性血红蛋白/血细胞比容水平>16.5g/dL/49%或女性血红蛋白/血细胞比容水平>16g/dL/48%，则可考虑进行初步诊断；建议但不强制进行骨髓检查以确认形态学异常。
异常核型见于 15%-20%的患者，最常见的单一异常为+9（5%）、丢失 Y 染色体（4%）、+8（3%）和 20q-（3%）。
超过 50%的患者存在除 JAK2 以外的 DNA 序列变异/突变，最常见的是 TET2（18%）和 ASXL1（15%）。预后不良的突变包括 SRSF2、IDH2、RUNX1 和 U2AF1，合并发生率为 5%-10%。
中位生存时间为 15 年，但年龄≤40 岁的患者生存时间超过 35 年。影响生存的危险因素包括年龄较大、白细胞增多、异常核型和存在不良突变。20 年血栓形成、PV 后 MF 或 AML 的风险分别为 26%、16%和 4%。
考虑两个风险类别：高（年龄>60 岁或有血栓形成史）和低（无两个危险因素）。动脉血栓形成的其他预测因素包括心血管危险因素，静脉血栓形成的其他预测因素包括绝对中性粒细胞计数较高和 JAK2V617F 等位基因负荷较高。
目前治疗的目标是预防血栓形成。定期放血，血细胞比容目标<45%，结合每日一次或两次阿司匹林（81mg）治疗，如果没有禁忌症，是所有患者治疗的基础，无论风险类别如何。细胞减少治疗保留用于高危疾病，首选药物为羟基脲和聚乙二醇干扰素-α，二线药物为白消安和鲁索替尼。此外，有静脉血栓形成史的患者建议进行全身抗凝治疗。
目前，我们不认为 JAK2V617F 等位基因负荷的药物诱导降低（通常不完整，不仅见于聚乙二醇干扰素，也见于鲁索替尼和白消安）是疾病修饰活性的指标，除非伴有细胞遗传学和独立证实的形态学缓解。因此，我们不使用特定参数来影响治疗选择。目前的综述还包括妊娠、脾静脉血栓形成、瘙痒、围手术期护理和 PV 后 MF 等情况下的具体治疗策略。
