New graft manipulation strategies improve the outcome of mismatched stem cell transplantation in children with primary immunodeficiencies.
Mismatched stem cell transplantation
T-cell receptor αβ/CD19
cord
graft-versus-host disease
immune reconstitution
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
10
06
2018
revised:
11
01
2019
accepted:
17
01
2019
pubmed:
8
2
2019
medline:
19
5
2020
entrez:
8
2
2019
Statut:
ppublish
Résumé
Mismatched stem cell transplantation is associated with a high risk of graft loss, graft-versus-host disease (GvHD), and transplant-related mortality. Alternative graft manipulation strategies have been used over the last 11 years to reduce these risks. We investigated the outcome of using different graft manipulation strategies among children with primary immunodeficiencies. Between 2006 and 2017, 147 patients with primary immunodeficiencies received 155 mismatched grafts: 30 T-cell receptor (TCR) αβ/CD19-depleted grafts, 43 cord blood (CB) grafts (72% with no serotherapy), 17 CD34 The estimated 8-year survival of the entire cohort was 79%, transplant-related mortality was 21.7%, and the graft failure rate was 6.7%. Posttransplantation viral reactivation, grade II to IV acute graft-versus-host disease (aGvHD), and chronic graft-versus-host disease (cGvHD) complicated 49.6%, 35%, and 15% of transplantations, respectively. Use of TCRαβ/CD19 depletion was associated with a significantly lower incidence of grade II to IV aGvHD (11.5%) and cGvHD (0%), although with a greater incidence of viral reactivation (70%) in comparison with other grafts. T-cell immune reconstitution was robust among CB transplants, although with a high incidence (56.7%) of grade II to IV aGvHD. Stable full donor engraftment was significantly greater at 80% among TCRαβ Rapidly accessible CB and haploidentical grafts are suitable alternatives for patients with no HLA-matched donor. Cord transplantation without serotherapy and TCRαβ
Sections du résumé
BACKGROUND
Mismatched stem cell transplantation is associated with a high risk of graft loss, graft-versus-host disease (GvHD), and transplant-related mortality. Alternative graft manipulation strategies have been used over the last 11 years to reduce these risks.
OBJECTIVE
We investigated the outcome of using different graft manipulation strategies among children with primary immunodeficiencies.
METHODS
Between 2006 and 2017, 147 patients with primary immunodeficiencies received 155 mismatched grafts: 30 T-cell receptor (TCR) αβ/CD19-depleted grafts, 43 cord blood (CB) grafts (72% with no serotherapy), 17 CD34
RESULTS
The estimated 8-year survival of the entire cohort was 79%, transplant-related mortality was 21.7%, and the graft failure rate was 6.7%. Posttransplantation viral reactivation, grade II to IV acute graft-versus-host disease (aGvHD), and chronic graft-versus-host disease (cGvHD) complicated 49.6%, 35%, and 15% of transplantations, respectively. Use of TCRαβ/CD19 depletion was associated with a significantly lower incidence of grade II to IV aGvHD (11.5%) and cGvHD (0%), although with a greater incidence of viral reactivation (70%) in comparison with other grafts. T-cell immune reconstitution was robust among CB transplants, although with a high incidence (56.7%) of grade II to IV aGvHD. Stable full donor engraftment was significantly greater at 80% among TCRαβ
CONCLUSIONS
Rapidly accessible CB and haploidentical grafts are suitable alternatives for patients with no HLA-matched donor. Cord transplantation without serotherapy and TCRαβ
Identifiants
pubmed: 30731121
pii: S0091-6749(19)30187-3
doi: 10.1016/j.jaci.2019.01.030
pii:
doi:
Substances chimiques
Antigens, CD19
0
CD19 molecule, human
0
Receptors, Antigen, T-Cell, alpha-beta
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
280-293Subventions
Organisme : Department of Health
ID : RP-2014-05-007
Pays : United Kingdom
Informations de copyright
Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.