Viral reactivations and associated outcomes in the context of immune reconstitution after pediatric hematopoietic cell transplantation

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:140

Article

Admiraal, Rick^1,2  de Koning, Coco C. H.¹  Lindemans, Caroline A.²  Bierings, Marc B.²  Wensing, Annemarie M. J.³  Versluys, A. Birgitta²  Wolfs, Tom F. W.⁴  Nierkens, Stefan¹  Boelens, Jaap Jan^1,2 

[1] Univ Med Ctr Utrecht, Lab Translat Immunol, Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, Pediat Blood & Marrow Transplantat Program, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands

[3] Univ Med Ctr Utrecht, Virol, Dept Med Microbiol, Utrecht, Netherlands

[4] Univ Med Ctr Utrecht, Dept Pediat Infect Dis, Utrecht, Netherlands

关键词: Viral reactivations;    hematopoietic cell transplantation;    immune reconstitution;    clinical outcomes;   

DOI  :  10.1016/j.jaci.2016.12.992

来源: Elsevier

【 摘 要 】

Background: Viral reactivations (VRs) after hematopoietic cell transplantation (HCT) contribute to significant morbidity and mortality. Timely immune reconstitution (IR) is suggested to prevent VR. Objectives: We 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. Methods: In 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. Results: Two 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 x 10(6) 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. Conclusion: These 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.

【 授权许可】

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