Risk factors for post‐transplant Epstein‐Barr virus events in pediatric recipients of hematopoietic stem cell transplants

AbstractBackgroundEpstein‐Barr virus (EBV) can cause severe disease following hematopoietic stem cell transplant (HSCT), including post‐transplant lymphoproliferative disorder (PTLD). The objective was to analyze risk factors associated with post‐transplant EBV outcomes among pediatric allogeneic HSCT recipients.MethodsWe used data from 156 pediatric allogeneic HSCT recipients enrolled in the Canadian multicenter TREASuRE study. Cox and Prentice‐Williams‐Petersen models were used to analyze risk factors for post‐transplant EBV events including occurrence and recurrence of EBV DNAemia, increase in EBV viral load (EBV‐VL), and preemptive use of rituximab, an effective therapy against PTLD.ResultsFemales were at higher risk for increasing EBV‐VL (adjusted hazard ratio (HR) = 2.83 [95% confidence intervals (CI): 1.33–6.03]) and rituximab use (HR = 3.08 [1.14–8.30]), but had the same EBV DNAemia occurrence (HR = 1.21 [0.74–1.99]) and recurrence risks (HR=1.05 [0.70–1.58]) compared to males. EBV DNAemia was associated with recipient pre‐transplant EBV seropositivity (HR = 2.47 [1.17–5.21]) and with graft from an EBV‐positive donor (HR = 3.53 [1.95–6.38]). Anti‐thymocyte globulin (ATG) was strongly associated with all EBV outcomes, including the use of rituximab (HR = 5.33 [1.47–19.40]). Mycophenolate mofetil (MMF) significantly decreased the risk of all EBV events including the rituximab use (HR = 0.13 [0.03–0.63]).ConclusionThis study in pediatric allogeneic HSCT patients reveals a reduced risk of all EBV outcomes with the use of MMF. Risk factors for EBV events such as EBV‐VL occurrence and recurrence include EBV positivity in the donor and recipient, and use of ATG, whereas risk factors for the most severe forms of EBV outcome (EBV‐VL and the use of rituximab) include female sex and ATG use.