Excellent T-cell reconstitution and survival provided ATG exposure is low or absent 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 relation between ATG exposure, IR and clinical outcomes. All pediatric patients receiving a first CBT between 2004-2015 at the University Medical Center Utrecht were included. ATG-exposure measures were determined with a validated PK-model. Main outcome of interest was early CD4+ IR, defined as CD4+ T-cell counts over 50x10(6)/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, 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 CB transplant predicted successful CD4+ IR. Adjusted probability on CD4+ IR was reduced with 26% for every 10 points increase in AUC after CBT (hazard ratio (HR) 0.974, p<0.0001). Chances on EFS were higher in patients with successful CD4+ IR (HR 0.26, p<0.0001) and lower ATG exposure after CBT (HR 1.005, p=0.0071). 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.