Emapalumab therapy for hemophagocytic lymphohistiocytosis before reduced-intensity transplantation improves chimerism.

Autor:	Verkamp 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., Jodele S; 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., Sabulski A; 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., Marsh R; 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., Kieser P; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH., Jordan MB; 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 Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Dec 19; Vol. 144 (25), pp. 2625-2636.
DOI:	10.1182/blood.2024025977
Abstrakt:	Abstract: 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. (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
Databáze:	MEDLINE
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