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Lymphoproliferative Disorders After Solid Organ Transplantation—Classification, Incidence, Risk Factors, Early Detection and Treatment Options

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  • Published:
Pathology & Oncology Research

Abstract

Posttransplant lymphoproliferative disorder (PTLD) is a heterogeneous disease group of benign and malignant entities. The new World Health Organisation classification introduced in 2008 distinguishes early lesions, polymorphic, monomorphic and classical Hodgkin lymphoma-type PTLD. Based on the time of appearance, early and late forms can be identified.

PTLDs are the second most frequent posttransplantation tumors in adulthood, and the most frequent ones in childhood. The incidence varies with the transplanted organ—from 1%–2% following kidney transplantation to as high as 10% following thoracic organ transplantation—due to different intensities in immunosuppression. Immunocompromised state and Epstein-Barr virus (EBV) infection are the two major risk factors.

In Europe and the US approximately 85% of PTLDs are of B-cell origin, and the majority are EBV-associated. Symptoms are often unspecific; extranodal, organ manifestations and central nervous system involvement is common. Early lesions respond well to a decrease in immunosuppression. Malignant entities are treated with rituximab, chemotherapy, radiotherapy and surgical therapy. Adoptive T-cell transfer represents a promising therapeutic approach. The prognosis is favorable in early PTLD, and poor in late PTLD. Five-year survival is 30% for high-grade lymphomas. The prognosis of EBV-negative lymphomas is worse.

Lowering the risk of PTLD may be achieved by low dose maintenance immunosuppression, immunosuppressive drugs inhibiting cell proliferation, and special immunotherapy (e.g. interleukin-2 inhibitors). Early detection is especially important for high risk—e.g. EBV-negative—patients, where the appearance of EBV-DNA and the increase in its titer may help.

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Abbreviations

ATG:

Anti-thymocyte globulin

CMV:

Cytomegalovirus

CNI:

Calcineurin inhibitor

CNS:

Central nervous system

CTL:

Cytotoxic T-lymphocyte

DLBCL:

Diffuse large B-cell lymphoma

DNA:

Deoxyribonucleic acid

EBNA:

Epstein-Barr nuclear antigen

EBV:

Epstein-Barr virus

FDG-PET:

Fluorodeoxyglucose positron emission tomography

HIV:

Human immunodeficiency virus

HLA:

Human leukocyte antigen

HSCT:

Hematopoietic stem cell transplantation

HTLV:

Human T-cell leukemia virus

IL:

Interleukin

LMP:

Latent membrane protein

mTOR:

Mammalian target of rapamycin

NK:

Natural killer

PCR:

Polymerase chain reaction

PSI:

Proliferation signal inhibitor

PTLD:

Posttransplant lymphoproliferative disorders

SOT:

Solid organ transplantation

UNOS:

United Network for Organ Sharing

WHO:

World Health Organisation

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Authors and Affiliations

  1. Department of Transplantation and Surgery, Semmelweis University, Baross u. 23, Budapest, H-1082, Hungary

    Gyula Végső

  2. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

    Melinda Hajdu & Anna Sebestyén

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  1. Gyula Végső
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Correspondence to Gyula Végső.

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Végső, G., Hajdu, M. & Sebestyén, A. Lymphoproliferative Disorders After Solid Organ Transplantation—Classification, Incidence, Risk Factors, Early Detection and Treatment Options. Pathol. Oncol. Res. 17, 443–454 (2011). https://doi.org/10.1007/s12253-010-9329-8

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  • DOI: https://doi.org/10.1007/s12253-010-9329-8

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