T-replete HLA-matched grafts vs T-depleted HLA-mismatched grafts in inborn errors of immunity.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
22 02 2022
22 02 2022
Historique:
received:
18
12
2020
accepted:
07
11
2021
pubmed:
1
1
2022
medline:
27
4
2022
entrez:
31
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34972212
pii: 483293
doi: 10.1182/bloodadvances.2020004072
pmc: PMC8864655
doi:
Substances chimiques
Antigens, CD19
0
Receptors, Antigen, T-Cell, alpha-beta
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1319-1328Subventions
Organisme : Wellcome Trust
ID : 204721/Z/16/Z
Pays : United Kingdom
Informations de copyright
© 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.
Références
J Clin Immunol. 2020 Jan;40(1):24-64
pubmed: 31953710
Front Immunol. 2017 Oct 11;8:1272
pubmed: 29075259
Br J Haematol. 2011 Apr;153(2):244-52
pubmed: 21382020
Bone Marrow Transplant. 2020 May;55(5):929-938
pubmed: 31740766
J Clin Immunol. 2013 Jan;33(1):8-13
pubmed: 23011479
Transpl Infect Dis. 2018 Feb;20(1):
pubmed: 29178554
Haematologica. 2016 Jun;101(6):680-7
pubmed: 27252513
J Allergy Clin Immunol. 2018 Apr;141(4):1417-1426.e1
pubmed: 28780238
Blood. 2019 Jun 6;133(23):2546-2549
pubmed: 30952673
Blood. 2011 Apr 21;117(16):4367-75
pubmed: 21325599
N Engl J Med. 2014 Jul 24;371(4):339-48
pubmed: 25054717
Leukemia. 2017 May;31(5):1145-1153
pubmed: 27811849
Blood Cells Mol Dis. 2008 Jan-Feb;40(1):76-83
pubmed: 17977031
Blood. 2017 Aug 3;130(5):677-685
pubmed: 28588018
Bone Marrow Transplant. 2018 Mar;53(3):264-273
pubmed: 29269793
J Immunol. 2004 Jan 1;172(1):644-50
pubmed: 14688377
Bone Marrow Transplant. 2020 Oct;55(10):1985-1995
pubmed: 32231250