Posttransplant lymphoproliferative disorder

By Sam Larkin

Posttransplant lymphoproliferative disorder (PTLD) comprises a heterogeneous group of lymphoid proliferations that develop in the setting of immunosuppression following solid organ transplantation (SOT) or allogeneic hematopoietic stem cell transplantation (allo-HSCT).¹ PTLD represents one of the most serious transplant-related malignancies, with risk varying by transplant type, degree of immunosuppression, recipient age, and Epstein–Barr virus (EBV) status.^2,3

Most cases arise from impaired T-cell immune surveillance, permitting uncontrolled proliferation of EBV-infected B cells; however, EBV-negative PTLD is increasingly recognized, particularly in late-onset disease.^3,4 According to the World Health Organization and International Consensus Classification, PTLD is classified as non-destructive, polymorphic, monomorphic, and classic Hodgkin lymphoma–type.^5,6

Clinical presentation is variable and may include:^1,3,4

• Fever
• Night sweats
• Weight loss
• Malaise
• Unexplained anemia
• Organ dysfunction
• Extranodal involvement

What are the main risk factors for PTLD?

Key risk factors for PTLD include:^2,3

• The intensity and duration of immunosuppression
• EBV seronegativity before transplantation
• EBV seromismatch between donor and recipient
• Primary EBV infection after transplant
• Younger age in SOT and allo-HSCT recipients
• Receipt of intestinal, lung, or multiorgan grafts

How does EBV status differ between early- and late-onset PTLD?

EBV status differs between early- and late-onset PTLD, with EBV implicated in most early-onset cases, with EBV-negative PTLD accounting for a substantial proportion of late-onset disease, often exhibiting biologic features similar to de novo diffuse large B-cell lymphoma.^3,4

What investigations are required to diagnose and stage PTLD?

Investigations required to diagnose PTLD include tissue biopsy with histopathological and immunophenotypic evaluation. Imaging with 18F-FDG PET-CT and EBV viral load assessment are also used to support staging and treatment planning.^2,3

What are the current treatment approaches for PTLD?

Current treatment approaches for PTLD include reduction of immunosuppression, which is the cornerstone of initial management in SOT recipients.^1-3 Rituximab is commonly used for CD20-positive disease in both SOT and allo-HSCT recipients, with chemotherapy considered for patients with high-risk disease or an inadequate response to initial treatment.^1-3 Monomorphic PTLD may require histology-specific chemoimmunotherapy, while cellular therapies and other emerging approaches may be considered for selected patients with refractory disease.^1-3

What treatment options are available for relapsed or refractory PTLD?

Treatment options for relapsed or refractory PTLD depend on PTLD subtype, prior therapy, and EBV status, and may include:^2,4

• Chemoimmunotherapy
• EBV-specific cellular therapies, such as tabelecleucel
• Participation in clinical trials
• Other emerging targeted approaches for patients with relapsed or refractory disease

References

1. Dharnidharka, 2024. Post-transplant lymphoproliferative disorders. https://www.doi.org/10.1016/j.semnephrol.2024.151503
2. Markouli, 2022. Recent advances in adult post-transplant lymphoproliferative disorder. https://www.doi.org/10.3390/cancers14235949
3. Vargas-Nieto, 2026. Post-transplant lymphoproliferative disorder after solid organ transplantation: A comprehensive review. https://www.doi.org/10.3389/frtra.2026.1869288
4. El-Mallawany, 2024. EBV and post-transplant lymphoproliferative disorder: A complex relationship. https://www.doi.org/10.1182/hematology.2024000583
5. Atallah-Yunes, 2025. Non-DLBCL monomorphic and Hodgkin lymphoma PTLD: Clinical insights and treatment strategies. https://www.doi.org/10.1182/bloodadvances.2025016930
6. Campo, 2022. The International Consensus Classification of Mature Lymphoid Neoplasms: A report from the Clinical Advisory Committee. https://www.doi.org/10.1182/blood.2022015851

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