Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder driven by interferon gamma (IFN-γ). Emapalumab, an anti–IFN-γ antibody, is approved for the treatment of patients with primary HLH. Hematopoietic stem cell transplantation (HSCT) is required for curing HLH. Reduced-intensity conditioning (RIC) HSCT is associated with improved survival but higher incidences of mixed chimerism and secondary graft failure. To understand the potential impact of emapalumab on post-HSCT outcomes, we conducted a retrospective study of pediatric patients with HLH receiving a first RIC-HSCT at our institution between 2014 and 2022 after treatment for HLH, with or without this agent. Mixed chimerism was defined as <95% donor chimerism and severe mixed chimerism as <25% donor chimerism. Intervention-free survival (IFS) included donor lymphocyte infusion, infusion of donor CD34-selected cells, second HSCT, or death within 5 years after HSCT. Fifty patients met the inclusion criteria; 22 received emapalumab within 21 days before the conditioning regimen, and 28 did not. The use of emapalumab was associated with a markedly lower incidence of mixed chimerism (48% vs 77%; P = .03) and severe mixed chimerism (5% vs 38%; P < .01). IFS was significantly higher in patients receiving emapalumab (73% vs 43%; P = .03). Improved IFS was even more striking in infants aged <12 months, a group at the highest risk for mixed chimerism (75% vs 20%; P < .01). Although overall survival was higher with emapalumab, this difference was not significant (82% vs 71%; P = .39). We show that the use of emapalumab for HLH before HSCT mitigates the risk of mixed chimerism and graft failure after RIC-HSCT.

中文翻译：

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低强度移植前噬血细胞性淋巴组织细胞增生症的 Emapalumab 治疗可改善嵌合体


噬血细胞性淋巴组织细胞增生症 （HLH） 是一种由干扰素 γ （IFN-γ） 驱动的高度炎症性疾病。Emapalumab 是一种抗 IFN-γ 抗体，被批准用于治疗原发性 HLH 患者。造血干细胞移植 （HSCT） 是治愈 HLH 所必需的。低强度调节 （RIC） HSCT 与生存率提高相关，但混合嵌合体和继发性移植失败的发生率更高。为了了解 emapalumab 对 HSCT 后结果的潜在影响，我们对 2014 年至 2022 年期间在我们机构接受首次 RIC-HSCT 的儿科患者进行了一项回顾性研究，这些患者在 HLH 治疗后接受或没有这种药物。混合嵌合体定义为 <95% 供体嵌合体，严重混合嵌合体定义为 <25% 供体嵌合体。无干预生存期 （IFS） 包括供体淋巴细胞输注、供体 CD34 选择细胞输注、第二次 HSCT 或 HSCT 后 5 年内死亡。50 例患者符合纳入标准;22 例在预处理方案前 21 天内接受了 emapalumab，28 例未接受。使用 emapalumab 与混合嵌合体的发生率显著降低相关 （48% vs 77%;P = .03） 和严重的混合嵌合体 （5% 对 38%;P < .01）.接受 emapalumab 的患者 IFS 显著升高 （73% vs 43%;P = .03）。改善的 IFS 在 <12 个月大的婴儿中更为明显，该组混合嵌合体的风险最高（75% 对 20%;P < .01）.尽管 emapalumab 的总生存期更高，但这种差异并不显著 （82% 对 71%;P = .39）。我们表明，在 HSCT 之前使用 emapalumab 治疗 HLH 可降低 RIC-HSCT 后混合嵌合体和移植物失败的风险。