Immune Modulation Properties of Zoledronic Acid on TcRγδ T-Lymphocytes After TcRαβ/CD19-Depleted Haploidentical Stem Cell Transplantation: An analysis on 46 Pediatric Patients Affected by Acute Leukemia.
Adolescent
Antigens, CD19
/ immunology
B-Lymphocytes
/ immunology
Child
Child, Preschool
Cohort Studies
Disease-Free Survival
Feasibility Studies
Female
Graft vs Host Disease
/ immunology
Hematopoietic Stem Cell Transplantation
/ methods
Humans
Immunologic Factors
/ administration & dosage
Infant
Leukemia, Myeloid, Acute
/ therapy
Lymphocyte Depletion
/ methods
Male
Receptors, Antigen, T-Cell, alpha-beta
/ immunology
Receptors, Antigen, T-Cell, gamma-delta
/ immunology
T-Lymphocytes
/ drug effects
Transplantation Conditioning
/ methods
Transplantation, Haploidentical
/ methods
Transplantation, Homologous
/ methods
Young Adult
Zoledronic Acid
/ administration & dosage
TcRαβ/CD19 cell depleted haploidentical stem cell transplantation
TcRγδ+ lymphocytes
acute leukemia
children
zoledronic acid
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
19
02
2020
accepted:
27
03
2020
entrez:
2
6
2020
pubmed:
2
6
2020
medline:
1
4
2021
Statut:
epublish
Résumé
TcRαβ/CD19-cell depleted HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents a promising new platform for children affected by acute leukemia in need of an allograft and lacking a matched donor, disease recurrence being the main cause of treatment failure. The use of zoledronic acid to enhance TcRγδ+ lymphocyte function after TcRαβ/CD19-cell depleted haplo-HSCT was tested in an open-label, feasibility, proof-of-principle study. Forty-six children affected by high-risk acute leukemia underwent haplo-HSCT after removal of TcRαβ+ and CD19+ B lymphocytes. No post-transplant pharmacological graft-versus-host disease (GvHD) prophylaxis was given. Zoledronic acid was administered monthly at a dose of 0.05 mg/kg/dose (maximum dose 4 mg), starting from day +20 after transplantation. A total of 139 infusions were administered, with a mean of 3 infusions per patient. No severe adverse event was observed. Common side effects were represented by asymptomatic hypocalcemia and acute phase reactions (including fever, chills, malaise, and/or arthralgia) within 24-48 h from zoledronic acid infusion. The cumulative incidence of acute and chronic GvHD was 17.3% (all grade I-II) and 4.8% (all limited), respectively. Patients given 3 or more infusions of zoledronic acid had a lower incidence of both acute GvHD (8.8 vs. 41.6%,
Identifiants
pubmed: 32477328
doi: 10.3389/fimmu.2020.00699
pmc: PMC7235359
doi:
Substances chimiques
Antigens, CD19
0
CD19 molecule, human
0
Immunologic Factors
0
Receptors, Antigen, T-Cell, alpha-beta
0
Receptors, Antigen, T-Cell, gamma-delta
0
Zoledronic Acid
6XC1PAD3KF
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
699Informations de copyright
Copyright © 2020 Merli, Algeri, Galaverna, Milano, Bertaina, Biagini, Girolami, Palumbo, Sinibaldi, Becilli, Leone, Boccieri, Grapulin, Gaspari, Airoldi, Strocchio, Pagliara and Locatelli.
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