title: Excellent T-cell reconstitution and survival depend on low ATG exposure after pediatric cord blood transplantation.
abstract: Successful immune reconstitution (IR) is associated with improved outcomes following pediatric cord blood transplantation (CBT). Usage and timing of anti-thymocyte globulin (ATG), introduced to the conditioning to prevent graft-versus-host disease and graft failure, negatively influences T-cell IR. We studied the relationships among ATG exposure, IR, and clinical outcomes. All pediatric patients receiving a first CBT between 2004 and 2015 at the University Medical Center Utrecht were included. ATG-exposure measures were determined with a validated pharmacokinetics model. Main outcome of interest was early CD4+IR, defined as CD4+T-cell counts >50 × 106/L twice within 100 days after CBT. Other outcomes of interest included event-free survival (EFS). Cox proportional-hazard and Fine-Gray competing-risk models were used. A total of 137 patients, with a median age of 7.4 years (range, 0.2-22.7), were included, of whom 82% received ATG. Area under the curve (AUC) of ATG after infusion of the cord blood transplant predicted successful CD4+IR. Adjusted probability on CD4+IR was reduced by 26% for every 10-point increase in AUC after CBT (hazard ratio [HR], 0.974; P < .0001). The chance of EFS was higher in patients with successful CD4+IR (HR, 0.26; P < .0001) and lower ATG exposure after CBT (HR, 1.005; P = .0071). This study stresses the importance of early CD4+IR after CBT, which can be achieved by reducing the exposure to ATG after CBT. Individualized dosing of ATG to reach optimal exposure or, in selected patients, omission of ATG may contribute to improved outcomes in pediatric CBT.
authors.affiliation: Pediatric Blood and Marrow Transplant Program.|Utrecht-Dendritic Cells Against Cancer, Laboratory of Translational Immunology, and.
authors.forename: Rick
authors.identifier: 0000-0003-1512-2791
authors.initials: R
authors.lastname: Admiraal
authors.affiliation: Pediatric Blood and Marrow Transplant Program.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Lindemans
authors.affiliation: Pediatric Blood and Marrow Transplant Program.|Utrecht-Dendritic Cells Against Cancer, Laboratory of Translational Immunology, and.
authors.forename: Charlotte
authors.initials: C
authors.lastname: van Kesteren
authors.affiliation: Pediatric Blood and Marrow Transplant Program.
authors.forename: Marc B
authors.initials: MB
authors.lastname: Bierings
authors.affiliation: Pediatric Blood and Marrow Transplant Program.
authors.forename: A Birgitta
authors.initials: AB
authors.lastname: Versluijs
authors.affiliation: Utrecht-Dendritic Cells Against Cancer, Laboratory of Translational Immunology, and.|Utrecht-Diagnostic Center for Diagnostic Advances in Immunology Research, Laboratory Translational Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Nierkens
authors.affiliation: Pediatric Blood and Marrow Transplant Program.|Utrecht-Dendritic Cells Against Cancer, Laboratory of Translational Immunology, and.
authors.forename: Jaap Jan
authors.identifier: 0000-0003-2232-6952
authors.initials: JJ
authors.lastname: Boelens
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D020127:Recovery of Function / Q000187:drug effects*; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D000961:Antilymphocyte Serum