Viral infections and immune reconstitution interaction after pediatric allogenic hematopoietic stem cell transplantation

Abstract

Background: Viral infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Although immune suppression plays a central role, the literature shows conflicting results on interplay between post-transplant immune reconstitution (IR) and viral infections.

Methods: We prospectively studied viral infections and IR in 30 pediatric patients undergoing allogenic HSCT, with a follow-up time of 24 months. In total, 1337 blood (CMV, EBV, HHV-6, ADV and BKV) and urine (BKV and JCV) virus samples were analyzed. IR including B-cells (CD19+), T cells (CD3+, CD4+, CD8+) and NK-cells were measured. Clinical outcomes included overall survival (OS), non-relapse mortality (NRM), graft-versus-host disease (GVHD) and occurrence of blood culture positive bacterial infections.

Results: We found BKV reactivation to be most frequent, 47% of the children had viremia and 77% viruria. The frequencies of CMV, HHV-6 and adeno viremia were 37%, 37% and 6%, respectively. Viremias beyond 3 months post-HSCT were uncommon. Factors such as GVHD, use of steroids, EBV and CMV infections and pre-transplant irradiation affected IR. No specific viral infection or IR related factor was associated to OS or NRM.

Conclusions: Viral infections and IR interact in a bi-directional manner. Accordingly, close follow-up of both IR and viral loads is warranted.

Keywords:

• Virus
• pediatric
• HSCT
• transplantation
• immune reconstitution

Acknowledgements

We thank research-nurse Pia Valle for indispensable assistance.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

The study was supported by grants of the Foundation for Pediatric Research, the Väre Foundation for Pediatric Cancer Research, Pediatric Research Center Helsinki, the Medical Society of Finland, the University of Helsinki Funds and the Cancer Society of Finland.