Children with Epstein-Barr virus (EBV) viremia after hematopoietic stem cell transplantation (HSCT) are at increased risk of post-transplant lymphoproliferative disease (PTLD). Our aim was to assess whether pre-emptive rituximab reduced EBV-viral load (EBV-VL) and the risk of developing PTLD.
We retrospectively included all children who had a positive EBV-VL within 12 months after an allogenic HSCT (2007-2015) in a single tertiary pediatric hospital. Whole blood EBV-VL was monitored weekly using a real time PCR, during the first 100 days after HSCT and then monthly until 6 months post-HSCT or until EBV-VL became undetectable. EBV-VL clearance was defined as 2 negative EBV-VL at least 1 week apart. Pre-emptive rituximab was defined as a treatment administered before the occurrence of PTLD. We determined the impact of pre-emptive rituximab on EBV-VL clearance, using a marginal structural cox model, adjusting for age at transplant, time between transplant and first positive EBV-VL, in-vivo T-cell depletion at induction, value of EBV-VL at the first dose of rituximab, and the EBV-VL value at the current and previous time point.
Of 214 children who underwent allogenic HSCT, EBV DNA was detected in 87 (41%) children. Children who received rituximab after diagnosis of PTLD were excluded, leading to a cohort of 78 children. Twenty-two (28%) children received pre-emptive rituximab. Mean (SD) age was similar in both groups (10  year). First post-transplant positive EBV-VL was earlier in the pre-emptive rituximab group (mean of 55  vs 113  days; p<0.05) and first positive EBV-VL was higher in the pre-emptive rituximab group (mean of 3.4 [0.6] versus 3.0 [0.6] log10/mL; p<0.05). In adjusted analyses, pre-emptive rituximab was associated with a higher likelihood of EBV-VL clearance (hazard ratio 1.86; 95% confidence interval 1.10-3.14; figure 1). Of the 10 children who developed PTLD, none had received pre-emptive rituximab.
EBV viremia is frequent in children with allogenic HSCT. Our results suggest that pre-emptive rituximab is associated with more rapid EBV-VL clearance. The effect of rituximab on the risk of PTLD needs to be better defined.
Figure 1: Inverse probability of EBV viremia clearance in children
P. Teira, None
C. Renaud, None
L. Kakinami, None
P. Ovetchkine, None
J. Autmizguine, None
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