Adapted Treatment of Epstein–Barr Virus Infection to Prevent Posttransplant Lymphoproliferative Disorder After Heart Transplantation

Abstract

Up to 35% of posttransplant lymphoproliferative disorder (PTLD) cases occur within 1 year of transplantation, and over 50% are associated with Epstein-Barr virus (EBV). EBV primary infection and reactivation are PTLD predictive factors, but there is no consensus for their treatment. We conducted a prospective single-center study on 299 consecutive heart-transplant patients treated with the same immunosuppressive regimen and monitored by repetitive EBV viral-load measurements and endomyocardial biopsies to detect graft rejection. Immunosuppression was tapered on EBV reactivation with EBV viral loads >10 5 copies/mL or primary infection. In the absence of response at 1 month or a viral load >10 6 copies/mL, patients received one rituximab infusion (375 mg/m 2 ). All patients responded to treatment without increased graft rejection. One primary infection case developed a possible PTLD, which completely responded to diminution of immunosuppression, and one patient, whose EBV load was unevaluable, died of respiratory complications secondary to PTLD. Compared with a historical cohort of 820 patients, PTLD incidence was decreased (p ¼ 0.033) by a per-protocol analysis. This is the largest study on EBV primary infection/reactivation treatment, the first using rituximab following solid organ transplantation to prevent PTLD and the first to demonstrate an acceptable tolerability profile in this setting.

Risk factors, diagnosis, and management of posttransplant lymphoproliferative disorder: improving patient outcomes with a multidisciplinary treatment approach

“…In comparison with the historical data, this study showed an effective prevention of EBV-associated PTLD by closely monitoring the EBV load and taking preemptive measures. 2 The limitation of this approach is the induction of B-lymphocyte depletion for ~6 months, leading to infection susceptibility. It does not restore the cellular immunity against EBV and thus does not provide long-term control of …”

“…It is usually associated with poor prognosis, with a 5-year overall survival rate of 20%. 1,2 Its occurrence depends on the type of transplant received, the type of immunosuppression, its intensity and duration, and the age of the recipient. …”

Enfermedad linfoproliferativa postrasplante de órgano sólido

“…Se ha evaluado prospectivamente la implementación de un protocolo de monitorización frecuente del VEB con reducción de la inmunosupresión guiada por la carga viral en pacientes pediátricos con trasplante de hígado (32) y se ha observado una diferencia estadís-ticamente significativa en la incidencia de ELPT, 16 % frente a 2 % (p < 0,05) con respecto a controles históri-cos. Además, se ha evaluado en adultos con trasplante cardíaco la combinación de monitorización de la carga viral de VEB, reducción de la inmunosupresión y uso anticipado de rituximab, lo cual también ha mostrado que reduce la incidencia de ELPT al comparar con controles históricos (33,34). Sin embargo, no hay ninguna recomendación actual sobre la periodicidad del seguimiento de la carga viral ni sobre las medidas terapéuticas para prevenir la aparición de ELPT; se requieren estudios prospectivos de alta calidad que evalúen la población en riesgo de ELPT y establezcan el papel de la monitorización y el tratamiento guiado por la carga viral de VEB.…”

Classification and Treatment of Posttransplant Lymphoproliferative Disorders

“…1). 25 With this algorithm, all cases of EBV reactivation or primary infection were controlled, and no patients developed PTLD. Table 3 shows varying published preventive or curative attitudes, depending on EBV VL.…”

“…Table 3 shows varying published preventive or curative attitudes, depending on EBV VL. 23,[25][26][27][28][29][30][31][32][33][34][35][36][37] Immunosuppression reduction. ISR is the widely acknowledged first-line approach, when possible.…”