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Open Access 01-04-2009 | Educational Feature

Post-transplant lymphoproliferative disease

Authors: Vikas R. Dharnidharka, Carlos E. Araya

Published in: Pediatric Nephrology | Issue 4/2009

Abstract

Post-transplant lymphoproliferative disease (PTLD) emerged in the mid-1990s as a major graft- and life-threatening complication of pediatric kidney transplantation. This condition, usually involving uncontrolled B lymphocyte proliferation, straddles the border between infection and malignancy, since Epstein–Barr virus (EBV) is intimately associated with the pathogenesis. PTLD is seen more in younger children (more likely to be EBV seronegative), Caucasian race, and in association with the more potent immunosuppression drugs. The clinical presentation typically involves multiple enlarged lymph nodes but varies based on localization of the lymphadenopathy. The diagnosis is based primarily on histopathological features. Treatment strategies include reduction of immunosuppression, use of anti-B cell antibodies, infusion of EBV-specific cytotoxic T lymphocytes, and chemotherapy. Many different strategies have been tried to prevent PTLD, ranging from serial EBV viral load monitoring and pre-emptive immunosuppression reduction to anti-viral prophylaxis. None of the major treatment or prevention strategies has been subject to randomized clinical trials, so their relative efficacy is still unknown. PTLD remains a risk factor for graft loss, though re-transplants have not, to date, been associated with repeat PTLD.

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1) Answer: c.

Rationale: cyclophosphamide is used as a component of the CHOP protocol of chemotherapy (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) for advanced PTLD, but not as prophylaxis. Reduction of immunosuppression and anti-viral agents can be used as either prevention or treatment strategies.

2) Answer: d.

Rationale: serial EBV PCR monitoring can be used to detect high viral loads prior to PTLD development and can potentially be used to monitor treatment efficacy, but it is not a treatment intervention itself.

3) Answer: c.

Rationale: central nervous system involvement has consistently been associated with the worst prognosis across different types of organ transplants. Allograft involvement is associated with a good prognosis in kidney transplants, though the prognosis is not as good when allograft failure is directly life-threatening, as in thoracic organ transplants.

4) Answer: d.

Rationale: male gender and Caucasian race have been found to be risk factors for PTLD. In general, the higher the burden of immunosuppression, the higher the risk for PTLD. However, MMF has not been associated with higher PTLD risk, though it has been associated with higher risk of CMV and BK virus infection.

5) Answer: a.

Rationale: EBV has been intimately linked to PTLD by epidemiologic, molecular and immunostaining analyses. CMV may be a co-factor, while urinary tract infection (UTI) and BK virus infection have not been associated with PTLD.

6) Answer: c.

Rationale: cellular immunity is thought to be more important in the control of proliferating infected B cells through EBV-specific cytotoxic T lymphocytes.

7) Answer: a.

Rationale: PTLD occurs more commonly within the first year of transplantation in children receiving kidney transplants, when more intense immunosuppression is used and EBV primary infection is more likely in a donor positive/recipient negative mismatch.

8) Answer: b.

Rationale: EBV viral loads may be elevated in the absence of PTLD and should not replace histologic examination of suspected sites of PTLD involvement.

Title: Post-transplant lymphoproliferative disease
Authors: Vikas R. Dharnidharka
Carlos E. Araya
Publication date: 01-04-2009
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 4/2009
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-007-0582-3

At a glance: The STEP trials

Springer Medicine

Post-transplant lymphoproliferative disease

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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