Optimizing anti-T-lymphocyte globulin dosing to improve long-term outcome after unrelated hematopoietic cell transplantation for hematologic malignancies.
bone marrow/hematopoietic stem cell transplantation
clinical research/practice
flow cytometry
graft-versus-host disease (GVHD)
graft-versus-leukemia (GVL)/graft versus tumor
hematology/oncology
immunosuppressant - polyclonal preparations: rabbit antithymocyte globulin
immunosuppression/immune modulation
mathematical model
translational research/science
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
10
06
2019
revised:
06
09
2019
accepted:
25
09
2019
pubmed:
10
10
2019
medline:
22
6
2021
entrez:
10
10
2019
Statut:
ppublish
Résumé
Prophylaxis of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HCT) remains challenging. Because prospective randomized trials of in-vivo T cell depletion using anti-T-lymphocyte globulin (ATLG) in addition to a calcineurin inhibitor and methotrexate (MTX) led to conflicting outcome results, we evaluated the impact of ATLG on clinical outcome, lymphocyte- and immune reconstitution survival models. In total, 1500 consecutive patients with hematologic malignancies received matched unrelated donor (MUD) HCT with cyclosporin and MTX (N = 723, 48%) or with additional ATLG (N = 777, 52%). In the ATLG cohort, grades III-IV acute (12% vs 23%) and extensive chronic GVHD (18% vs 34%) incidences were significantly reduced (P < .0001). Nonrelapse mortality (27% vs 45%) and relapse (30% vs 22%) differed also significantly. Event-free and overall survival estimates at 10 years were 44% and 51% with ATLG and 33% and 35% without ATLG (P < .002 and <.0001). A dose-dependent ATLG effect on lymphocyte- and neutrophil reconstitution was observed. At ATLG exposure, lymphocyte counts and survival associated through a logarithmically increasing function. In this survival model, the lymphocyte count optimum range at exposure was between 0.4 and 1.45/nL (P = .001). This study supports additional ATLG immune prophylaxis and is the first study to associate optimal lymphocyte counts with survival after MUD-HCT.
Identifiants
pubmed: 31597002
doi: 10.1111/ajt.15642
pii: S1600-6135(22)22232-1
doi:
Substances chimiques
Antilymphocyte Serum
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
677-688Subventions
Organisme : University of Duisburg-Essen UDE-IFORES
Pays : International
Organisme : Bundesministerium für Bildung und Forschung
ID : 031L0027
Pays : International
Informations de copyright
© 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.
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