Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea.
Expert Rev Hematol. 2022 Jul;15(7):573-581. doi: 10.1080/17474086.2022.2088499. Epub 2022 Jun 14.
Myelofibrosis (MF) is characterized by ineffective and hepatosplenic extramedullary hematopoiesis due to fibrotic changes in the bone marrow and systemic manifestations due to aberrant cytokine release. Ruxolitinib (RUX) is the first JAK1/JAK2 inhibitor that is clinically approved to treat splenomegaly by ameliorating inflammatory cytokines and myeloproliferation in MF.
Patients with less advanced MF may also achieve better outcome and successful treatment with RUX. However, approximately 40% of the patients failed to achieve a stable response or have shown to be intolerant to RUX, and most of them discontinued RUX. In patients who need to discontinue or reduce the dose of RUX for any reason, RUX is known to induce a paradoxical accumulation of JAK activation loop phosphorylation that is causing RUX discontinuation syndrome (RDS). To review the topic of MF and RUX, we searched relevant literatures using PubMed.
RUX treatment in lower IPSS risk patients who present with splenomegaly and disease-associated symptoms can be helpful. A careful discontinuation strategy with steroids may reduce the probability of RDS, and the recognition of RDS with early re-introduction of RUX is important in the treatment of severe cases of RDS.
骨髓纤维化（MF）的特征是由于骨髓纤维化改变导致无效和肝脾髓外造血，以及由于异常细胞因子释放导致全身表现。芦可替尼（RUX）是首个被临床批准用于治疗 MF 脾肿大的 JAK1/JAK2 抑制剂，可通过改善炎症细胞因子和骨髓增生来实现。
病情不太严重的 MF 患者也可能通过 RUX 获得更好的疗效和成功的治疗。然而，约 40%的患者未能达到稳定的反应或对 RUX 不耐受，且大多数患者停止了 RUX 治疗。在因任何原因需要停止或减少 RUX 剂量的患者中，已知 RUX 会诱导 JAK 激活环磷酸化的反常积累，从而导致 RUX 停药综合征（RDS）。为了回顾 MF 和 RUX 的相关主题，我们使用 PubMed 搜索了相关文献。
对于出现脾肿大和疾病相关症状且 IPSS 风险较低的患者，RUX 治疗可能会有所帮助。谨慎的停药策略联合类固醇可能会降低 RDS 的发生概率，及早重新引入 RUX 识别 RDS 对于治疗严重的 RDS 非常重要。
