当前位置: X-MOL 学术Blood › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Confirmed efficacy of etoposide and dexamethasone in HLH treatment: Long term results of the cooperative HLH-2004 study
Blood ( IF 20.3 ) Pub Date : 2017-12-21 , DOI: 10.1182/blood-2017-06-788349
Elisabet Bergsten 1, 2 , AnnaCarin Horne 1, 2 , Maurizio Aricó 3 , Itziar Astigarraga 4 , R. Maarten Egeler 5 , Alexandra H. Filipovich 6 , Eiichi Ishii 7 , Gritta Janka 8 , Stephan Ladisch 9 , Kai Lehmberg 8 , Kenneth L. McClain 10 , Milen Minkov 11 , Scott Montgomery 12, 13, 14 , Vasanta Nanduri 15 , Diego Rosso 16, 17, 18, 19 , Jan-Inge Henter 1, 2
Affiliation  

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. In the HLH-94 study, with an estimated 5-year probability of survival (pSu) of 54% (95% confidence interval, 48%-60%), systemic therapy included etoposide, dexamethasone, and, from week 9, cyclosporine A (CSA). Hematopoietic stem cell transplantation (HSCT) was indicated in patients with familial/genetic, relapsing, or severe/persistent disease. In HLH-2004, CSA was instead administered upfront, aiming to reduce pre-HSCT mortality and morbidity. From 2004 to 2011, 369 children aged <18 years fulfilled HLH-2004 inclusion criteria (5 of 8 diagnostic criteria, affected siblings, and/or molecular diagnosis in FHL-causative genes). At median follow-up of 5.2 years, 230 of 369 patients (62%) were alive (5-year pSu, 61%; 56%-67%). Five-year pSu in children with (n = 168) and without (n = 201) family history/genetically verified FHL was 59% (52%-67%) and 64% (57%-71%), respectively (familial occurrence [n = 47], 58% [45%-75%]). Comparing with historical data (HLH-94), using HLH-94 inclusion criteria, pre-HSCT mortality was nonsignificantly reduced from 27% to 19% (P = .064 adjusted for age and sex). Time from start of therapy to HSCT was shorter compared with HLH-94 (P =020 adjusted for age and sex) and reported neurological alterations at HSCT were 22% in HLH-94 and 17% in HLH-2004 (using HLH-94 inclusion criteria). Five-year pSu post-HSCT overall was 66% (verified FHL, 70% [63%-78%]). Additional analyses provided specific suggestions on potential pre-HSCT treatment improvements. HLH-2004 confirms that a majority of patients may be rescued by the etoposide/dexamethasone combination but intensification with CSA upfront, adding corticosteroids to intrathecal therapy, and reduced time to HSCT did not improve outcome significantly.

中文翻译:

证实依托泊苷和地塞米松在 HLH 治疗中的疗效:合作 HLH-2004 研究的长期结果

噬血细胞性淋巴组织细胞增生症 (HLH) 是一种危及生命的高炎症综合征,包括家族性/遗传性 HLH (FHL) 和继发性 HLH。在 HLH-94 研究中,估计 5 年生存概率 (pSu) 为 54%(95% 置信区间,48%-60%),全身治疗包括依托泊苷、地塞米松,以及从第 9 周开始的环孢素 A (CSA)。造血干细胞移植 (HSCT) 适用于家族性/遗传性、复发性或严重/持续性疾病的患者。在 HLH-2004 中,CSA 改为预先给药,旨在降低造血干细胞移植前的死亡率和发病率。从 2004 年到 2011 年,369 名 18 岁以下的儿童符合 HLH-2004 纳入标准(8 个诊断标准中的 5 个、受影响的兄弟姐妹和/或 FHL 致病基因的分子诊断)。中位随访 5.2 年,369 名患者中有 230 名 (62%) 存活(5 年 pSu,61%;56%-67%)。有 (n = 168) 和没有 (n = 201) 家族史/基因验证 FHL 的儿童的五年 pSu 分别为 59% (52%-67%) 和 64% (57%-71%)(家族性发生) [n = 47],58% [45%-75%])。与历史数据 (HLH-94) 相比,使用 HLH-94 纳入标准,HSCT 前死亡率从 27% 无显着降低至 19%(根据年龄和性别调整 P = .064)。与 HLH-94 相比,从开始治疗到 HSCT 的时间更短(根据年龄和性别调整 P = 020),报告的 HSCT 神经学改变在 HLH-94 中为 22%,在 HLH-2004 中为 17%(使用 HLH-94 纳入标准)。HSCT 后五年 pSu 总体为 66%(经验证的 FHL,70% [63%-78%])。其他分析提供了有关潜在的 HSCT 前治疗改进的具体建议。
更新日期:2017-12-21
down
wechat
bug