EBV and post-transplant lymphoproliferative disorder: a complex relationship.

Area of Science:

• Oncology
• Immunology
• Pathology

Background:

• Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of diseases arising from iatrogenic immune suppression.
• Epstein-Barr virus (EBV)-driven B-cell lymphoproliferation is the classic PTLD, encompassing nondestructive, polymorphic, and monomorphic EBV+ diffuse large B-cell lymphoma (DLBCL) PTLD.
• While EBV is a common driver, other factors contribute to PTLD heterogeneity, with or without EBV co-driving lymphoid neoplasia.

Purpose of the Study:

• To review the evolution of PTLD nomenclature, emphasizing precise subcategorization.
• To focus on PTLD in pediatric, adolescent, and young adult solid organ transplant recipients.
• To outline a conceptual framework for PTLD, including lymphoid hyperplasia, neoplasia, and malignancy, to guide treatment.

Main Methods:

• Review of contemporary PTLD nomenclature and classification.
• Analysis of treatment outcomes for different PTLD subtypes.
• Discussion of EBV's role and other lymphoid neoplasia drivers in PTLD.

Main Results:

• Quintessential EBV-associated PTLD, including monomorphic DLBCL, often responds to low-intensity therapies (e.g., reduced immunosuppression, rituximab).
• Approximately 30%-40% of quintessential PTLD cases are refractory to low-intensity treatments, necessitating intensive chemotherapy.
• Other monomorphic PTLD forms, similar to lymphomas in immunocompetent individuals, typically require lymphoma-specific treatments and are categorized as posttransplant lymphomas.

Conclusions:

• A conceptual framework of lymphoid hyperplasia, neoplasia, and malignancy aids in understanding PTLD variations.
• Risk stratification and evidence-based treatment strategies are informed by this framework.
• Precise subcategorization of PTLD is crucial for determining appropriate therapeutic approaches, distinguishing between EBV-driven PTLD and other posttransplant lymphomas.