Algorithm for the treatment of PTLD. Early clinical trial enrollment is pertinent to expand accessibility of treatment options. Reduction in immunosuppression (RIS; as tolerated to limit risk of GVHD or graft rejection) is an initial method of controlling EBV-associated PTLD. Rituximab should be initiated in both polymorphic and monomorphic PTLD, with evidence that complete response (CR) to rituximab alone should be treated with an extended course of rituximab. Without response to rituximab, chemotherapy should be added to the treatment regimen as well as the administration of ESTs (as available in clinical trials). ISH, in situ hybridization.