Rituximab for the Treatment of Refractory EBV Viremia and Prevention of PTLD in Pediatric Heart Transplant Recipients

Abstract

Purpose: Post-transplant lymphoproliferative disorder (PTLD) is a major contributor to post-transplant morbidity and mortality in pediatric heart transplant recipients. EBV viremia is associated with the development of PTLD in this population. We sought to evaluate the safety and efficacy of rituximab for the prophylactic treatment of refractory EBV viremia and prevention of PTLD in pediatric heart transplant recipients. Methods: Since 2010, all pediatric heart transplant patients at our institution with EBV viremia refractory to standard therapy (valganciclovir and IVIg) received rituximab 375 mg/m2. Time to peak response, length of response (need to resume EBV treatment), subsequent development of PTLD, significant infections within one year, and death after rituximab were assessed. Change from baseline EBV PCR after rituximab over time was evaluated using a multivariate adaptive regression splines model. Results: Twenty-seven doses of rituximab were administered to 12 children with refractory EBV viremia between 2010-2016. The median age at dosing was 8.4 years (range 2.5-19.3 years). The median time to peak response was 41 days. The median length of response was 198 days. Seven subjects required additional doses (range 1-7 doses) with a median time to repeat dose of 1.8 years (range 19 days - 3.9 years). None of the children developed PTLD after rituximab, including four subjects with a prior history of PTLD. Six (50%) subjects experienced a major infection within one year of rituximab. Sepsis (3 episodes) and pneumonia (4 episodes) were most common. One subject developed mucormycosis and died 415 days after administration of her fourth dose. Figure 1 shows the change from baseline EBV PCR after rituximab administration (R2= 0.41). Conclusion: Rituximab used for the treatment of refractory EBV viremia to prevent PTLD is effective, but close monitoring for serious infection is needed. A sustained response can be seen for many, but repeat dosing may be needed. (Figure presented).