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: HSCT; Virus; immune reconstitution; pediatric; transplantation.