Epstein-Barr Virus-Related B Cell Lymphoproliferative Disorder After Hematopoietic Stem Cell Transplantation

In 51 (33 adult-18 paediatric) allogeneic hematopoietic stem cell transplant recipients we aimed to evaluate: i) the incidence of EBV infection and potential risk factors; ii) the suitability of whole blood (WB) as clinical specimen to monitor the risk of patients to develop EBV-related post-transplant lymphoproliferative disorder (EBV-PTLD); iii) the clinical utility of combined virological-immunological monitoring; iv) the management of infection and the incidence of EBV-PTLD. Quantitative real-time PCR assay was performed on WB samples for all patients. EBV-DNA quantification also in peripheral blood mononuclear cells (PBMCs) samples was adopted for actively EBV infected patients. Immunological monitoring of infection was performed by Enzyme-linked ImmunoSPOT assay evaluating the EBV-specific cell-mediated immunity (CMI). The incidence of EBV infection was 51% and the frequency of EBV-PTLD was 3.9%. Reduced-intensity conditioning (RIC) in combination with in vivo T-cell depletion was associated with higher frequencies of infection (P=0.036). A significant correlation (P<0.001) between EBV-DNA levels in WB and PBMC samples was obtained in adult (r=0.787) and paediatric (r=0.976) patients. A similar kinetics of EBV-DNA in blood compartments was observed. Clinically, both specimen types appeared to be equally informative. The lack of EBV-specific CMI during/after active infection was associated with a higher median peak level of EBV-DNA in WB (P=0.013) and a greater severity of infection. The 54.5% of the patients without EBV-specific CMI needed anti-CD20 therapy and the 27.2% developed EBV-related complications, including a lethal PTLD. All patients with EBV-specific CMI controlled EBV replication and were asymptomatic. WB proved to be a suitable clinical specimen to monitor the risk of patients to develop EBV-related complications. RIC combined with in vivo T-cell depletion is a risk factor for the development of infection. EBV-specific CMI is a critical determinant in controlling the infection and consequently the EBV-related complications. Combined virological-immunological monitoring could improve the management of infection.