A pilot study of ruxolitinib as a front-line therapy for 12 children with secondary hemophagocytic lymphohistiocytosis.
A pilot study of ruxolitinib as a front-line therapy for 12 children with secondary hemophagocytic lymphohistiocytosis.
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鲁索替尼作为 12 名继发性噬血细胞性淋巴组织细胞增多症儿童一线治疗的初步研究。
DOI：
10.3324/haematol.2020.253781
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发表时间：
2021-07-01
期刊：
影响因子：
10.1
通讯作者：
Zhang R
中科院分区：
文献类型：
--
作者：
Zhang Q;Wei A;Ma HH;Zhang L;Lian HY;Wang D;Zhao YZ;Cui L;Li WJ;Yang Y;Wang TY;Li ZG;Zhang R
噬血细胞性淋巴组织细胞增多症（HLH）是一种免疫调节障碍，其特征是炎症细胞因子的过度产生。长期以来，HLH- 1994和HLH-2004方案的治疗建议一直用于HLH治疗，但一些患者仍然对常规治疗反应不佳或有不可接受的副作用。人们相信，直接针对疾病驱动途径的细胞因子靶向策略将是治疗HLH的有希望的选择。这项前瞻性研究旨在探讨ruxolitinib（一种Janus激酶1/2抑制剂）作为继发性HLH患儿一线治疗的有效性和安全性。本研究纳入12例未接受治疗的新诊断患者，中位随访时间为8.2（7.1-12.0）个月，包括8例eb病毒相关HLH (EBV-HLH)， 2例自身炎症性疾病（AID）相关HLH， 2例病因不明。患者接受口服ruxolitinib，剂量分别为2.5 mg， 5 mg或10 mg，每日两次，根据体重连续28天。治疗结束时（第28天）的总缓解率为83.3%（12人中有10人），完全缓解（CR）为66.7%（12人中有8人），部分缓解（PR）为8.3%（12人中有1人），HLH改善为8.3%（12人中有1人）。在达到CR的患者中，87.5%（8名患者中的7名）的CR状态维持超过6个月，1名EBV-HLH患者在CR后复发。对于EBV-HLH亚组，8名患者均对ruxolitinib有反应，CR率为75%，PR率为25%。两名与艾滋病相关的HLH患者有完全不同的反应，其中一名显示HLH异常很快逆转，另一名没有改善，两例病因不明的病例也是如此。没有反应或停用鲁索利替尼的患者对随后的HLH-1994方案均有良好反应。预期6个月无事件生存率为58.3±10.2%。没有严重的不良反应报告。本研究为鲁索利替尼靶向治疗儿童继发性HLH的可能性提供了进一步的支持。本研究已在中国临床试验注册平台（http://www.chictr.org.cn/）注册为临床试验政府号：ChiCTR2000029977。
Hemophagocytic lymphohistiocytosis (HLH) is an immune-regulatory disorder characterized by excessive production of inflammatory cytokines. The treatment recommendations of the HLH- 1994 and HLH-2004 protocols have long been used in HLH therapy, but some patients still do not respond well to or have unacceptable side effects from conventional therapies. It is believed that cytokine-targeted strategies that directly target disease-driving pathways will be promising options for HLH. This prospective study aimed to investigate the efficacy and safety of ruxolitinib, a Janus kinase 1/2 inhibitor, as a front-line therapy in children with secondary HLH. Twelve newly diagnosed patients without previous treatment were enrolled in this study with a median follow-up of 8.2 (range, 7.1-12.0) months, including eight cases of Epstein-Barr virus associated HLH (EBV-HLH), two cases of autoinflammatory disorder (AID)- associated HLH, and two cases of unknown etiology. Patients received oral ruxolitinib dosed on 2.5 mg, 5 mg or 10 mg twice daily depending on the body weight for 28 consecutive days. The overall response rate at the end of treatment (day 28) was 83.3% (ten of 12), with 66.7% (eight of 12) in complete response (CR), 8.3% (one of 12) in partial response (PR), and 8.3% (one of 12) in HLH improvement. Among the patients achieving CR, 87.5% (seven of eight) maintained CR condition more than 6 months, and one patient with EBV-HLH relapsed following CR. For the EBV-HLH subgroup, all eight patients responded to ruxolitinib, with a CR rate of 75% and a PR rate of 25%. Two patients with AID-associated HLH had quite different responses, with one showing reversal of the HLH abnormalities soon and the other showing no improvement, as did the two cases of unknown etiology. Patients who had no response or discontinued ruxolitinib all responded well to the subsequent HLH-1994 regimen. The expected 6-month event-free survival rate was 58.3±10.2%. No serious adverse effects were reported. Our study provides further support for the possibility of ruxolitinib targeted therapy for secondary HLH in children. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as clinicaltrials gov. Identifier: ChiCTR2000029977.
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DOI：
10.4049/jimmunol.1401867
发表时间：
2015-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Villarino AV;Kanno Y;Ferdinand JR;O'Shea JJ
通讯作者：
O'Shea JJ
DOI：
10.1002/mpo.1189
发表时间：
2001-08-01
期刊：
MEDICAL AND PEDIATRIC ONCOLOGY
影响因子：
--
作者：
Kitazawa, J;Ito, E;Imashuku, S
通讯作者：
Imashuku, S
影响因子：
3.2
作者：
Marsh, Rebecca A.;Allen, Carl E.;McClain, Kenneth L.;Weinstein, Joanna L.;Kanter, Julie;Skiles, Jodi;Lee, Nadine D.;Khan, Shakila P.;Lawrence, Julia;Mo, Jun Q.;Bleesing, Jack J.;Filipovich, Alexandra H.;Jordan, Michael B.
通讯作者：
Jordan, Michael B.
影响因子：
7.5
作者：
Lounder, Dana T.;Bin, Qiong;Jordan, Michael B.
通讯作者：
Jordan, Michael B.
影响因子：
12.8
作者：
Gonzalez Vicent, Martay;Molina, Blanca;Angel Diaz, Miguel
通讯作者：
Angel Diaz, Miguel