Ruxolitinib in Alleviating the Cytokine Storm of Hemophagocytic Lymphohistiocytosis
Ruxolitinib in Alleviating the Cytokine Storm of Hemophagocytic Lymphohistiocytosis
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DOI：
10.1542/peds.2019-1301
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发表时间：
2020-08-01
期刊：
影响因子：
8
通讯作者：
Shi Xiaodong
中科院分区：
文献类型：
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作者：
Li Jianguo;Zhou Zhixuan;Shi Xiaodong
通过这项研究，我们证实了鲁索利替尼治疗HLH的疗效，并开启了HLH糖皮质激素非激素化治疗。噬血细胞性淋巴组织细胞增多症是一种罕见的危及生命的综合征，分为原发性和继发性两种。继发性HLH通常由自身免疫性疾病、感染或癌症引起。继发性HLH的一线治疗是HLH2004方案，包括地塞米松、依托泊苷和支持性治疗。然而，多达30%的患者，特别是儿科患者，对一线治疗仍然没有反应，HLH儿童的死亡率达到50%。此外，一些有特殊情况的儿童，如活动性病毒感染，不适合接受免疫抑制剂治疗。最近发现了几种促促黄体生成素的细胞因子，包括干扰素-γ、白介素2和白介素6。Janus激酶1和2控制许多细胞因子的信号传递，特别是干扰素-γ、白介素2和白介素6。Janus kinase1和2抑制剂，如ruxolitinib，已经成功地用于治疗小鼠的HLH。在这里，我们报告一名男孩，被诊断为HLH和高滴度的乙肝病毒DNA拷贝，在接受Ruxolitinib治疗后病情迅速好转，HLH的细胞因子风暴得到缓解。鲁索利替尼治疗5天后，使用恩替卡韦，血清乙肝病毒DNA滴度结果为阴性。经过3个月的鲁索利替尼治疗和1年的随访，男孩的病情持续缓解。在本研究中，鲁索利替尼可能是一种一线药物，可以缓解HLH的细胞因子风暴。这种疗法可能会开启非糖皮质激素治疗的时代，这对儿童尤其有意义，因为它避免了糖皮质激素的副作用。
With this study, we confirmed the therapeutic effect of ruxolitinib in HLH and ushered in a glucocorticosteroid-free treatment of HLH. Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome classified into primary HLH and secondary HLH. Secondary HLH is always caused by autoimmune disease, infections, or cancer. The first-line therapy for secondary HLH is the HLH 2004 protocol, including dexamethasone, etoposide, and supportive therapy. However, up to 30% of patients, especially pediatric patients, remain unresponsive to first-line treatment, and the mortality rate reaches 50% in children with HLH. Furthermore, some children who have special conditions, such as an active virus infection, are not suitable for immunosuppressants treatment. Recently, several HLH-promoting cytokines have been identified, including interferon-gamma, interleukin-2, and interleukin-6. Janus kinase 1 and 2 control the signaling of many cytokines, notably interferon-gamma, interleukin-2, and interleukin-6. Janus kinase 1 and 2 inhibitors, such as ruxolitinib, have been successfully used to treat HLH in mice. Here, we report that a boy, diagnosed with HLH and high titer of hepatitis B virus-DNA copies, improved quickly, and the cytokine storm of HLH was alleviated after receiving ruxolitinib. Five days after ruxolitinib treatment, entecavir was introduced and serum titer results of hepatitis B virus-DNA returned negative. With 3 months of ruxolitinib treatment and following-up 1 year, the boy's situation maintained sustained remission. In this study, it is suggested that ruxolitinib might be a first-line drug, which could alleviate the cytokine storm of HLH. This treatment may be ushering in the age of glucocorticosteroid-free HLH treatment, which is particularly meaningful for children because it avoids the side effects of glucocorticosteroid.