• Rick Admiraal, Coco C H de Koning, Caroline A Lindemans, Marc B Bierings, WensingAnnemarie M JAMJVirology, Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands., A Birgitta Versluys, WolfsTom F WTFWDepartment of Pediatric Infectious Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands., Stefan Nierkens, and Jaap Jan Boelens.
• Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands; Pediatric Blood and Marrow Transplantation Program, University Medical Centre Utrecht, Utrecht, The Netherlands.
• J. Allergy Clin. Immunol. 2017 Dec 1; 140 (6): 1643-1650.e9.

BackgroundViral reactivations (VRs) after hematopoietic cell transplantation (HCT) contribute to significant morbidity and mortality. Timely immune reconstitution (IR) is suggested to prevent VR.ObjectivesWe studied the relation between IR (as a continuous predictor over time) and VR (as a time-varying predictor) and the relation between VR and other clinical outcomes.MethodsIn this retrospective analysis all patients receiving a first HCT between January 2004 and September 2014 were included. IR (CD3/CD4/CD8 T, natural killer, and B cells) was measured biweekly until 12 weeks and monthly thereafter. Main outcomes of interest were VR of adenovirus, EBV, human herpesvirus 6 (HHV6), cytomegalovirus (CMV), and BK virus screened weekly. Clinical outcomes included overall survival (OS), event-free-survival, nonrelapse mortality (NRM), and graft-versus-host disease. Cox proportional hazard and Fine and Gray competing risk models were used.ResultsTwo hundred seventy-three patients (age, 0.1-22.7 years; median follow-up, 58 months) were included. Delayed CD4 reconstitution predicted reactivation of adenovirus (hazard ratio [HR], 0.995; P = .022), EBV (HR, 0.994; P = .029), and HHV6 (HR, 0.991; P = .012) but not CMV (P = .31) and BK virus (P = .27). Duration of adenovirus reactivation was shorter with timely CD4 reconstitution, which was defined as 50 × 106 cells/L or greater within 100 days. Adenovirus reactivation predicted lower OS (HR, 2.17; P = .0039) and higher NRM (HR, 2.96; P = .0008). Concomitant CD4 reconstitution abolished this negative effect of adenovirus reactivation (OS, P = .67; NRM, P = .64). EBV and HHV6 reactivations were predictors for the occurrence of graft-versus-host disease, whereas CMV and BK virus reactivation did not predict clinical outcomes.ConclusionThese results stress the importance of timely CD4 reconstitution. Strategies to improve CD4 reconstitution can improve HCT outcomes, including survival, and reduce the need for toxic antiviral therapies.Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

22 keywords...

hide…