Post-transplantation lymphoproliferative disorder in the Epstein-Barr virus-naïve lung transplant recipient.

Abstract

Post-transplantation lymphoproliferative disorder (PTLD) is a widely recognized and often catastrophic complication of organ transplantation. The incidence of PTLD after lung transplantation ranges from 6.2 to 9.4% and is two-fold higher than that seen after organ transplantation of other organs. Primary Epstein-Barr virus (EBV) infection is a major risk factor for PTLD, but the incidence of PTLD in EBV seronegative (EBV-) patients seems to vary with type of organ transplant. The goal of this study was to quantify the risk of PLTD based on pre-lung transplantation EBV serostatus in lung transplant patients. Pre- and post-lung transplant serostatus was defined in 80 patients, and our six cases of PTLD occurred in this group. Six of 94 lung transplant patients (6.4%) who survived > 1 mo developed PTLD. All cases of PTLD involved thoracic structures at presentation and occurred in the first post-operative year. Patients who were EBV- before lung transplant were much more likely to develop PTLD than those who were seropositive (EBV+) (five of 15 [33%] versus one of 60 [< 2%], p < 0.001). Consistent with the prevailing adult (donor) EBV+ rate (85%), two of our EBV-patients remained EBV-after lung transplant. Therefore, the rate of PTLD was 42% in those with primary EBV infection. As compared with EBV-patients that remained tumor-free, those who developed PLTD had similar levels of immunosuppressants and doses of anti-viral therapy. We conclude that PLTD occurs predominantly in EBV-naïve patients (risk approximately 1/3). EBV-patients should be monitored more closely after lung transplantation and, possibly, managed with lower immunosuppression. Our data also suggest that anti-viral therapy alone does not decrease the incidence of PTLD in high risk patients, PTLD can be successfully treated in most cases, and EBV-naïve patients should not be excluded from lung transplant because their risk of death from PTLD is < 15%.

Posttransplant Lymphoproliferative Disorders in Lung Transplant Patients: The Cleveland Clinic Experience

“…Secondly, PTLDs in LTx patients appear to occur very early after transplant (median time 7 mo) compared with non-LTx patients (median time, 41 mo), which is consistent with the case in the previous literature (12,23,24,30). In addition, these PTLDs also appear to be clinically aggressive, with 5 of 8 patients dying of their PTLD.…”

“…The incidence of PTLDs appears to depend on several factors, including age, pretransplantation EBV status, immunosuppression regimen, and transplanted organ (5,29,30). The incidence of PTLD in LTx patients varies in the literature from 6 to 10% (12,24). Montone et al (23) reported a very high incidence of 20% that seems to be an outlier.…”

“…We recently encountered two PTLDs in LTx patients that occurred early after transplantation and demonstrated an aggressive clinical behavior. On review of the literature, we found a varied experience, with some reporting a high incidence of PTLD in LTx patients, whereas others found a much lower incidence (12,(22)(23)(24).…”

“…Large series reporting the incidence and presentation of PTLDs exclusively in lung transplant (LTx) patients are few (12,(22)(23)(24). We recently encountered two PTLDs in LTx patients that occurred early after transplantation and demonstrated an aggressive clinical behavior.…”

Valganciclovir for the Suppression of Epstein-Barr Virus Replication

“…Various studies have therefore examined the use of prophylactic antiviral therapy in transplant recipients to reduce the risk of PTLD. Results from studies have been varied, with multiple early studies of anti-viral prophylaxis detecting no impact on PTLD incidence [27,28]. However, one early study was able to detect a reduction in PTLD incidence from 3.9% to 0.5% of SOT recipients who received either acyclovir (administered orally four times daily) or ganciclovir (administered intravenously) while they received highly immunosuppressive antilymphocyte antibody therapy [29].…”