Toward Functional Immune Monitoring in Allogeneic Stem Cell Transplant Recipients

Serious viral infections, due to delayed immune reconstitution, are a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Thus, many transplant centers prospectively track cellular immune recovery by evaluating absolute cell numbers and the phenotypic profile of reconstituting T cell subsets to identify individuals who are at highest risk of infection. Conventional assessments, however, fail to measure either the antigen specificity or functional capacity of reconstituting cells-both factors that correlate with endogenous antiviral protection. In this pilot study, we sought to address this limitation by prospectively investigating the tempo of endogenous immune reconstitution in a cohort of 23 pediatric HSCT patients using both quantitative (flow cytometry) and qualitative (IFNγ ELISpot) measures, which we correlated with either the presence or absence of infections associated with cytomegalovirus, adenovirus, Epstein-Barr virus, BK virus, human herpes virus 6, respiratory syncytial virus, parainfluenza, influenza, and human metapneumovirus. We present data spanning 12 months post-transplant demonstrating the influence of conditioning on immune recovery and highlighting the differential impact of active viral replication on the quantity and quality of reconstituting cells. Judicious use of standard (phenotypic) and novel (functional) monitoring strategies can help guide the clinical care and personalized management of allogenic HSCT recipients with infections.