The Impact of EBV Status on Characteristics and Outcomes of Posttransplantation Lymphoproliferative Disorder

The molecular pathogenesis of posttransplant diffuse large B cell lymphoma (PT‐DLBCL) is largely unknown. We have recently shown that Epstein‐Barr virus–positive (EBV+) and –negative (EBV−) PT‐DLBCL have distinct gene expression profiles, and the transcriptomic profile of EBV− PT‐DLBCL is similar to that of DLBCL in immunocompetent individuals (IC‐DLBCL). To validate these observations at the genomic level, we performed array–comparative genome hybridization (aCGH) analysis of 21 EBV+ PT‐DLBCL, 6 EBV− PT‐DLBCL, and 11 control IC‐DLBCL, and subsequently combined genomic and transcriptomic data. The analysis showed that EBV+ and EBV− PT‐DLBCL have distinct aCGH profiles and shared only one recurrent imbalance. EBV− PT‐DLBCL, however, displayed at least 10 aberrations recurrent in IC‐DLBCL, among which characteristic gain of 3/3q and 18q, and loss of 6q23/TNFAIP3 as well as 9p21/CDKN2A. The most prevalent aberration in EBV+ PT‐DLBCL was gain/amplification of 9p24.1 targeting PDCD1LG2/PDL2. Our data indicate that the FOXP1 oncogene and the tumor suppressor CDKNA2 implicated in EBV− DLBCL, do not play a critical role in the pathogenesis of EBV+ PT‐DLBCL. Altogether, genomic profiling of PT‐/IC‐DLBCL confirms that EBV− and EBV+ PT‐DLBCL are distinct entities, while EBV− PT‐DLBCL has features in common with IC‐DLBCL. These findings support the hypothesis that EBV− PT‐DLBCL are de novo lymphomas in transplant recipients.

Section: Discussionsupporting

confidence: 70%

EBV-Positive and EBV-Negative Posttransplant Diffuse Large B Cell Lymphomas Have Distinct Genomic and Transcriptomic Features

Ferreiro

Morscio

Dierickx

et al. 2016

“…14 The incidence of PTLD rose in the 1990s, before dropping in the subsequent decade, [14][15][16] although the incidence of EBV-negative PTLD may be increasing, both as a proportion and absolute incidence. 17 Most EBV+PTLDs occur within the first 3 years, 18,19 whereas EBV-negative PTLDs have a steady incidence in each year, 18,20 as shown by Morton et al ( Figure 2).…”

Section: Incidencementioning

confidence: 85%

“…The incidence density for PTLD ranges from 1.58 per 1000 person-years (kidney) to 2.24 (heart), 2.44 (liver), and 5.72 (lung). 17 Most EBV+PTLDs occur within the first 3 years, 18,19 whereas EBV-negative PTLDs have a steady incidence in each year, 18, 20 as shown by Morton et al ( Figure 2). 11 Registry data also show a higher incidence in the first year (called early PTLD), and then a second peak at later years ( Figure 2).…”

Section: Incidencementioning

confidence: 86%

Comprehensive review of post–organ transplant hematologic cancers

Dharnidharka

2018

A higher risk for a variety of cancers is among the major complications of posttransplantation immunosuppression. In this part of a continuing series on cancers posttransplantation, this review focuses on the hematologic cancers after solid organ transplantation. Posttransplantation lymphoproliferative disorders (PTLDs), which comprise the great majority of hematologic cancers, represent a spectrum of conditions that include, but are not limited to, the Hodgkin and non-Hodgkin lymphomas. The oncogenic Epstein-Barr virus is a key pathogenic driver in many PTLD cases, through known and unknown mechanisms. The other hematologic cancers include leukemias and plasma cell neoplasms (multiple myeloma and plasmacytoma). Clinical features vary across malignancies and location. Preventive screening strategies have been attempted mainly for PTLDs. Treatments include the chemotherapy regimens for the specific cancers, but also include reduction of immunosuppression, rituximab, and other therapies.

“…two cases of 250 transplanted over 17 years); for recipients of two or more versus three or more islet infusions, we estimate the incidence of PTLD at 0.9% (i.e. Both cases were DLBCL with no evidence of EBV or CMV occurring beyond 1 year posttransplantation, the most common histologic subtype and presentation of PTLD in SOT (8,25,26). 1/85), respectively.…”

Section: Discussionmentioning

confidence: 99%

Posttransplant Lymphoproliferative Disorder After Clinical Islet Transplantation: Report of the First Two Cases

Peters

Olateju

Deschênes

et al. 2017

We report the first two cases of posttransplant lymphoproliferative disorder (PTLD) in recipients of islet transplants worldwide. First, a 44-year-old recipient of three islet infusions developed PTLD 80 months after his initial transplantation, presenting with abdominal pain and diffuse terminal ileum thickening on imaging. He was treated with surgical excision, reduction of immunosuppression, and rituximab. Seven months later, he developed central nervous system PTLD, presenting with vertigo and diplopia; immunosuppression was discontinued, resulting in graft loss, and he was given high-dose methotrexate and underwent consolidative autologous stem cell transplantation. He remains in remission 37 months after the initial diagnosis. Second, a 58-year-old female recipient of two islet infusions developed PTLD 24 months after initial islet infusion, presenting with pancytopenia secondary to extensive bone marrow involvement. Immunosuppression was discontinued, resulting in graft loss, and she received rituximab and chemotherapy, achieving complete remission. Both patients were monomorphic B cell PTLD subtype by histology and negative for Epstein-Barr virus in tissue or blood. These cases document the first occurrences of this rare complication in islet transplantation, likely secondary to prolonged, intensive immunosuppression, and highlight the varying clinical manifestations of PTLD. Further studies are needed to determine incidence rate and risk factors in islet transplantation.