Molecular Targeting of Post-transplant Lymphoproliferative Disorders

Abstract

Post-transplant lymphoproliferative disorders (PTLD) represent a heterogeneous group of life-threatening lymphoproliferative disorders that can be observed in a transplant recipient. PTLD can occur in patients after solid organ transplantation (SOT) because of immunosuppression to prevent graft rejection (Penn et al. 1969), and continues to be a major cause of morbidity and mortality seen in about 10% of pediatric SOT recipients. There is a higher incidence in children following SOT than in adults (Ho et al. 1988; Swerdlow et al. 2000), with highest incidence of 20% following heart-lung transplant. PTLD occurs in hematopoietic stem cell transplantation (HSCT) recipients secondary to the immunosuppression of pre-HSCT preparative regimens, and the post-HSCT immunosuppression to prevent graft vs host disease (GVHD). PTLD in HSCT occurs at a lower rate than following SOT (approximately 1%), with the vast majority occurring within 6 months following HSCT (Bhatia et al. 1996; Curtis et al. 1999). Accordingly, few cases of PTLD have been reported after autologous HSCT (Lones et al. 2000; Nash et al. 2003). PTLD is associated with Epstein–Barr virus (EBV) and inadequate EBV immunity in the majority of cases. PTLD following HSCT is essentially all EBV-associated. EBV-negative PTLD occurs following SOT in as many as 30% of cases. (Leblond et al. 2001). The pathogenesis, treatment strategies and outcome differ from EBV-positive PTLD, as EBV-negative disease tends to require more aggressive therapy and portends a worse prognosis. This chapter will focus on EBV positive PTLD and molecularly targeted therapies in its prevention and treatment.