EBV and posttransplantation lymphoproliferative disease: what to do?

Abstract

This review summarizes the available evidence and outlines our approach to the prophylaxis and management of posttransplantation lymphoproliferative disorder (PTLD) in adult solid organ transplantation recipients. We attempt to reduce immunosuppression as tolerated in every patient with suspected PTLD in close cooperation with their transplantation physician. There is no evidence to guide the decision when to initiate further treatment; we usually wait no longer than 4 weeks and always initiate further therapy unless there is a complete or at least good partial remission. If clinical and histological findings indicate rapidly progressive disease, we initiate additional therapy significantly earlier. CD20-positive PTLD accounts for approximately 75% of PTLD cases. Outside of clinical trials, we currently regard sequential therapy with rituximab and CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone/ prednisolone) chemotherapy as standard evidence-based treatment for CD20-positive PTLD unresponsive to immunosuppression. We also discuss our approach to the rare instance of adults with PTLD associated with primary EBV infection, localized (stage I) disease, rare PTLD subtypes, and refractory/relapsed disease based on the available retrospective data and our own experience. In addition to immunotherapy and chemotherapy, this includes local therapy approaches such as surgery and radiotherapy in stage I disease, plasmacytoma-like PTLD, and primary CNS PTLD. We also provide our view on the current indications for the use of allogeneic cytotoxic T cells, even though this treatment modality is so far unavailable in our clinical practice.

Recent Progress in Xenotransplantation, with Emphasis on Virological Safety

“…There is evidence that PLHV-1 is associated with post-transplant lymphoproliferative disease (PTLD) in miniature pigs following allogeneic hematopoietic stem-cell transplantation [75,76]. The clinical symptoms of experimental porcine PTLD, such as fever, lethargy, anorexia, high white blood cell count, and palpable lymph nodes, are similar to those of human PTLD, which was linked to the human herpesvirus Epstein-Barr virus, now designated HHV-4 [77]. Evidence of productive PLHV-1 infection was not detected in recipient baboons receiving different organs from transgenic pigs for up to 6 months of transplant function [78].…”

Risk factors, diagnosis, and management of posttransplant lymphoproliferative disorder: improving patient outcomes with a multidisciplinary treatment approach

“…110 Radiotherapy also plays an important role in some emergency setting (ie, cord compression). Moreover, it can be useful in palliation of symptoms due to local complication of PTLD.…”

“…Adjuvant systemic therapy with rituximab, although not evidence based, should be considered in patients with polymorphic PTLD. 110 …”

Enfermedad linfoproliferativa postrasplante de órgano sólido

“…Trasplante multivisceral > intestino > pulmón > corazón/pulmón > corazón > riñón Presencia de malignidades pretrasplante La incidencia de ELPT tiene una distribución bimodal, con un pico temprano (primeros dos años postrasplante), y uno tardío, con diferencias en los factores de riesgo y los hallazgos histológicos, lo que sugiere mecanismos diferentes para su producción. Los casos tempranos parecen ser mediados principalmente por la infección con VEB en el contexto de la inmunosupresión profunda, y los tardíos se relacionan con la inmunosupresión prolongada, la edad avanzada y probablemente la exposición a agentes específicos, lo cual se ha evidenciado en diferentes estudios (5)(6)(7)(8).…”

“…En el momento del diagnóstico se debe hacer tomografía computarizada de cuello, tórax, abdomen y pelvis, para clasificar la extensión, evaluar la estrategia de tratamiento y como base para el seguimiento de la respuesta. 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).…”