T-replete HLA-matched grafts vs T-depleted HLA-mismatched grafts in inborn errors of immunity.

Autor:	Lum SH; Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Greener S; Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Perez-Heras I; Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Drozdov D; Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Payne RP; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Watson H; Blood Sciences., Carruthers K; Newcastle Advanced Therapies, and., January R; Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Nademi Z; Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Owens S; Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Williams E; Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Waugh S; Microbiology and Virology Department, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; and., Burton-Fanning S; Microbiology and Virology Department, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; and., Leahy TR; Department of Paediatric Immunology, CHI at Crumlin, Dublin, Ireland., Cant A; Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Abinun M; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Flood T; Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Hambleton S; Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Gennery AR; Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Slatter M; Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2022 Feb 22; Vol. 6 (4), pp. 1319-1328.
DOI:	10.1182/bloodadvances.2020004072
Abstrakt:	Hematopoietic cell transplantation (HCT) has become standard-of-care for an increasing number of inborn errors of immunity (IEI). This report is the first to compare transplant outcomes according to T-cell-replete (ie, T-replete) HLA-matched grafts using alemtuzumab (n = 117) and T-cell-depleted (ie, T-depleted) HLA-mismatched grafts using T-cell receptor-αβ (TCRαβ)/CD19 depletion (n = 47) in children with IEI who underwent first HCT between 2014 and 2019. All patients received treosulfan-based conditioning except patients with DNA repair disorders. For T-replete grafts, the stem cell source was marrow in 25 (21%) patients, peripheral blood stem cell (PBSC) in 85 (73%), and cord blood in 7 (6%). TCRαβ/CD19 depletion was performed on PBSCs from 45 haploidentical parental donors and 2 mismatched unrelated donors. The 3-year overall survival (OS) and event-free survival for the entire cohort were 85% (77%-90%) and 79% (69%-86%), respectively. Analysis according to age at transplant revealed a comparable 3-year OS between T-replete grafts (88%; 76%-94%) and T-depleted grafts (87%; 64%-96%) in younger patients (aged <5 years at HCT). For older patients (aged >5 years), the OS was significantly lower in T-depleted grafts (55%; 23%-78%) compared with T-replete grafts (87%; 68%-95%) (P = .03). Grade III to IV acute graft-versus-host disease was observed in 8% of T-replete marrow, 7% of T-replete PBSC, 14% of T-replete cord blood, and 2% of T-depleted PBSC (P = .73). Higher incidence of viremia (P < .001) and delayed CD3 reconstitution (P = .003) were observed after T-depleted graft HCT. These data indicate that mismatched donor transplant after TCRαβ/CD19 depletion represents an excellent alternative for younger children with IEI in need of an allograft. (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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