Verkamp Bethany, Jodele Sonata, Sabulski Anthony, Marsh Rebecca, Kieser Pearce, Jordan Michael B
Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH.
Division of Clinical Development, Pharming Healthcare Inc, Warren, NJ.
Blood. 2024 Dec 19;144(25):2625-2636. doi: 10.1182/blood.2024025977.
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.
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）驱动的过度炎症性疾病。抗IFN-γ抗体emapalumab已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。减低强度预处理（RIC）HSCT与生存率提高相关，但混合嵌合体和继发性移植物失败的发生率更高。为了解emapalumab对HSCT后结局的潜在影响，我们对2014年至2022年期间在我们机构接受首次RIC-HSCT治疗HLH的儿科患者进行了一项回顾性研究，这些患者在治疗HLH时使用或未使用该药物。混合嵌合体定义为供体嵌合体<95%，严重混合嵌合体定义为供体嵌合体<25%。无干预生存期（IFS）包括供体淋巴细胞输注、输注供体CD34选择细胞、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emapalumab治疗，28例未接受。emapalumab的使用与混合嵌合体（48%对77%；P = 0.03）和严重混合嵌合体（5%对38%；P < 0.01）的发生率显著降低相关。接受emapalumab治疗的患者IFS显著更高（73%对43%；P = 0.03）。在<12个月的婴儿中，IFS的改善更为显著，这是混合嵌合体风险最高的一组（75%对20%；P < 0.01）。尽管emapalumab治疗的总体生存率更高，但差异不显著（82%对71%；P = 0.39）。我们表明，在HSCT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。
