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

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.

Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression

“…[3][4][5][6][7] Similarly, effective salvage therapies are lacking for subsets of DLBCL, such as the mediastinal variant of DLBCL, and other aggressive NHLs, such as gray zone lymphomas (B-cell lymphoma unclassifiable with features intermediate between DLBCL and classical Hodgkin lymphoma [HL]) and posttransplant lymphoproliferative disorders (PTLDs). [8][9][10][11][12] CD30 is expressed in a variety of malignancies 13,14 and is present in 14% to 25% of DLBCL patients, depending on the cutoff used to assign positivity. [15][16][17] Hu et al reported a unique gene expression profile for de novo DLBCL expressing CD30 in greater than 20% of cells.…”

Primary Intrarenal Posttransplant Lymphoproliferative Disorder Detected by Surveillance Protocol Biopsy

“…Primary intrarenal localization is extremely rare and is generally diagnosed late, because of ambiguous clinical presentation (2). We detected primary intrarenal lymphoplasmacellular early PTLD in a 5-year-old kidney transplant recipient by renal allograft protocol biopsy.…”

Enfermedad linfoproliferativa postrasplante de órgano sólido

“…Puede ocurrir en cualquier momento después del trasplante. El tercer grupo corresponde a la ELPT monomorfa de células B o T (22)(23)(24). En la tabla 2 se muestra la clasificación con los diferentes subtipos así como la asociación descrita en cada uno de ellos con el VEB.…”

“…Los estudios de imágenes del sistema nervioso central y el del líquido cefalorraquídeo se hacen según la indicación clínica (5,28). La tomografía computarizada por emisión de positrones (PET-CT) puede ser una alternativa útil, especialmente en los casos de presentaciones atípicas, tanto para evaluar el estadio como para el seguimiento, especialmente en los linfomas B difusos de células grandes y en los linfomas Hodgkin (23,29). Se debe clasificar a los pacientes usando el sistema Ann Arbor, se acuerdo con la localización del compromiso y la presencia de síntomas (30).…”