Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Hematology Oncology Center, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Br J Haematol. 2021 May;193(4):761-768. doi: 10.1111/bjh.17331. Epub 2021 Feb 9.
We performed a multicentre, non-randomised trial (NCT03533790) to investigate the efficacy of ruxolitinib combined with the doxorubicin-etoposide-methylprednisolone (Ru-DEP) regimen as a salvage therapy for refractory/relapsed haemophagocytic lymphohistiocytosis (HLH). All patients failing to achieve a complete or partial response 2 weeks after initial HLH-94/HLH-04 regimen or relapsed after remission were enrolled in the study between June 2018 and June 2019. The efficacy was evaluated 2 weeks after initiating Ru-DEP salvage therapy. Fifty-four eligible patients with refractory/relapsed (R/R) HLH were enrolled. One case could not be evaluated for efficacy. Excluding 12 patients who had previously received the DEP regimen, the overall response rate was 32 of 41 (78·0%) patients, with eight of 41 (19·5%) achieving complete response and 24 of 41 (58·5%) attaining a partial response. Of the R/R HLH patients who had previously received the DEP regimen, 7 of 12 (58·3%) achieved a partial response. Ferritin and soluble CD25 concentrations were significantly lower (P < 0·05), while the platelet count increased significantly (P = 0·034), and triglycerides decreased significantly (P = 0·002) compared with those before treatment. The Ru-DEP regimen may be a safe and effective salvage therapy, remaining effective in refractory/relapsed HLH following DEP treatment, especially in macrophage activation syndrome. In addition, the regimen can be considered for patients with contraindications to glucocorticoid, especially those with gastrointestinal bleeding.
我们进行了一项多中心、非随机试验（NCT03533790），以研究鲁索利替尼联合多柔比星-依托泊苷-甲基强的松龙（Ru-DEP）方案作为难治/复发噬血细胞性淋巴组织细胞增生症（HLH）挽救治疗的疗效。所有在初始 HLH-94/HLH-04 方案治疗 2 周后未达到完全或部分缓解或缓解后复发的患者均在 2018 年 6 月至 2019 年 6 月期间入组该研究。在开始 Ru-DEP 挽救治疗 2 周后评估疗效。54 例难治/复发（R/R）HLH 患者符合入组条件，其中 1 例无法评估疗效。排除 12 例先前接受过 DEP 方案的患者后，41 例患者的总缓解率为 32 例（78.0%），其中 8 例（19.5%）达到完全缓解，24 例（58.5%）达到部分缓解。在先前接受过 DEP 方案的 R/R HLH 患者中，7 例（58.3%）达到部分缓解。与治疗前相比，铁蛋白和可溶性 CD25 浓度显著降低（P<0.05），血小板计数显著升高（P=0.034），甘油三酯显著降低（P=0.002）。Ru-DEP 方案可能是一种安全有效的挽救治疗方法，在 DEP 治疗后难治/复发 HLH 中仍然有效，特别是在巨噬细胞活化综合征中。此外，该方案可考虑用于对糖皮质激素有禁忌证的患者，尤其是有胃肠道出血的患者。
