Reconstitution of adenovirus-specific cell-mediated immunity in pediatric patients after hematopoietic stem cell transplantation

Abstract

Adenovirus (adv) is a significant cause of morbidity and mortality in pediatric hematopoietic stem cell transplant recipients, and control of infection seems to require antigen-specific T cells. We evaluated the recovery of adv-specific cellular immunity in this patient population related to degree of T-cell immunosuppressive therapy and compared this to adv cellular immunity of normal donors. Over 12 months, we monitored for adv DNA in stool and blood of patients and in the blood of a normal donor group. Twenty-two pediatric hematopoietic stem cell transplant (HSCT) patients (14 months-20 years) who received matched-related (MRD n=6), mismatched related (Haplo n=6) or matched unrelated donor (MUD n=10) grafts, were followed and results compared to healthy controls (n=8). Adv was detected by polymerase chain reaction in blood and/or stool from 81.8% of patients on at least one occasion post-HSCT, but only 68% of patients developed symptomatic adv infections. Recovery of adv-specific T cells was significantly delayed in the MUD and Haplo recipients, whereas recovery in the MRD group was similar to levels detected in healthy donors within 30 days post-transplant. In conclusion, recipients of alternative donor transplants at our institution have significantly delayed adv-specific cellular immune recovery, which correlates to an increased risk of adv-associated morbidity and mortality.