Risk factors for early‐onset and late‐onset post‐transplant lymphoproliferative disorder in kidney recipients in the United States

Abstract

Summary Incidence of post-transplant lymphoproliferative disorder (PTLD) is bimodal, suggesting distinct early-onset and late-onset subtypes. We evaluated differences in risk factors for early-onset and late-onset PTLD in a retrospective cohort study of U.S. kidney transplant recipients using data from the Scientific Registry of Transplant Recipients (N=156,740, 1999–2007). Multivariate hazard ratios (HRs) for risk factors were estimated using proportional hazards models. For early-onset PTLD, significantly increased risk was associated with young age at transplantation (HR 3.97 for <20 vs. 20–50 years), non-Hispanic white race/ethnicity (HR 1.82), and seronegativity for Epstein Barr virus (EBV) and cytomegalovirus at transplantation (HRs 3.13 and 1.49, respectively). By comparison, younger and older age (HRs 2.68 and 1.28 for <20 and >50, respectively, vs. 20–50 years) and non-Hispanic white race/ethnicity (HR 1.77) increased late-onset PTLD risk. The association with young age was weaker for late-onset than early-onset PTLD (p=0.06), and EBV and cytomegalovirus serostatus were not associated with late-onset PTLD risk. These results support somewhat different etiologies for early-onset and late-onset PTLD. For early-onset PTLD, associations with young age and EBV seronegativity highlight the etiologic role of primary EBV infection. For late-onset PTLD, higher risk with older age is consistent with lymphoma patterns in the general population.

Posttransplant Lymphoproliferative Disorders Following Solid Organ Transplantation

“…(Nee et al, 2011) Quinlan et al found that non-Hispanic whites were at significantly higher risk of early-onset and late-onset PTLD than other racial or ethnic groups. (Quinlan et al, 2011) In the same study it was also demonstrated that CMVseronegativity was associated with increased early-onset PTLD risk. (Quinlan et al, 2011) However, it seems that the role of CMV and HCV as risk factors for PTLD is controversial, as is that of herpes simplex or simian virus infections.…”

“…(Caillard et al, 2005;van Leeuwen et al, 2009) This difference may be related to different eras of treatment and increasing experience with antibody-based induction therapies, leading to an attenuation of associated PTLD risks. (Quinlan et al, 2011) In contrast, PTLD occurred 2 to 3-fold more frequently after receipt of OKT3 than with other drugs. (Opelz & Dohler, 2004;Taylor et al, 2005) Gajarski et al report that as induction agents thymoglobulin and IL-2R antagonists had the lowest associated PTLD rates compared to OKT3, attributing this to its long-lasting depletional effects on CD-3 positive Tlymphocytes.…”

“…This difference is due to higher doses of immunosuppression and induction treatment required following heart and lung transplantation. (Quinlan et al, 2011;Taylor et al, 2005) Another difference noted is the origin of the PTLD in renal transplantation--PTLD of donor origin has been described. (Olagne et al, 2011) …”

Significance of Asymptomatic Persistent Epstein-Barr Viral Load in Pediatric Renal Transplant Recipients: North American Pediatric Renal Trials and Collaborative Studies Report

“…In this study young, Caucasian and EBV mismatched children were more likely and African-American children were less likely to develop PVL. These demographic and clinical characteristics have been identified as risk factors for PTLD in the previous studies; however, these characteristics have not been previously assessed for development of EB PVL [1,[8][9][10]. Concern has been raised that thymoglobulin may play a role in the development of PTLD as it has been shown to deplete poly functional T cells in HIV infected kidney transplant recipients and activate EBV replication [11].…”

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).…”