Diagnosis Of Post-transplant Lymphoproliferative Disease Research Articles

Age and Epstein-Barr viral load at diagnosis of post-transplant lymphoproliferative disease are associated with patient survival in kidney transplant recipients.

This study investigated variables associated with mortality in kidney transplant recipients (KTRs) diagnosed with post-transplant lymphoproliferative disease (PTLD) and a simultaneous Epstein-Barr virus (EBV) viremia. This was a retrospective cohort study enrolling KTRs diagnosed with PTLD between 2018 and 2020. Outcome: death within two years after diagnosis. Among 1,625 KTRs who collected EBV viremia (by PCR, 2018-2020) for any reason, 238 (14.6%) had a positive viral load and 41 (17.2%) simultaneous PTLD. These 41 patients were 40.1 years old at diagnosis and 8.6 years after transplantation; 26.8% were induced with rATG and 92.7% were maintained on tacrolimus and azathioprine (TAC/AZA) as immunosuppressive regimen. Lymph nodes (75.6%) was the most common site of PTLD, followed by the gastrointestinal tract (48.8%), with 61.0% at Lugano stage IV and 80.5% monomorphic PTLD. The mean EBV viral load was 12,198 IU/mL. One- and two-year patient survival post-diagnosis was 60.4% and 46.8%, respectively. In the Cox regression analysis, age at PTLD diagnosis (HR for each year = 1.039; p < 0.001) and EBV viral load (HR for each log = 1.695; p = 0.026) were associated with risk of death. This study suggests that in patients predominantly on TAC/AZA, PTLD with simultaneous EBV positive viral load is a late event, and worse survival is associated with older age and EBV viral load at diagnosis.

Outcomes for patients with EBV-positive PTLD post-allogeneic HCT after failure of rituximab-containing therapy

Epstein–Barr virus-positive (EBV+) post-transplant lymphoproliferative disease (PTLD) is an ultra-rare and aggressive condition that may occur following allogeneic hematopoietic cell transplant (HCT) due to immunosuppression. Approximately half of EBV+ PTLD cases are relapsed or refractory (R/R) to initial rituximab-containing therapy. There are limited treatment options and no standard of care for patients with R/R EBV+ PTLD, and little is known about their treatment history and outcomes. We performed a multinational, multicenter, retrospective chart review of patients with R/R EBV+ PTLD following HCT to describe patients’ demographic and disease characteristics, treatment history, and overall survival (OS) from rituximab failure. Among 81 patients who received initial treatment with rituximab as monotherapy (84.0%) or in combination with chemotherapy (16.0%), median time from HCT to PTLD diagnosis was 3.0 months and median OS was 0.7 months. Thirty-six patients received a subsequent line of treatment. The most frequent causes of death were PTLD (56.8%), graft-versus-host disease (13.5%) and treatment-related mortality (10.8%). In multivariate analysis, early PTLD onset and lack of response to initial treatment were associated with mortality. This real-world study demonstrates that the prognosis of patients with R/R EBV+ PTLD following HCT remains poor, highlighting the urgent unmet medical need in this population.

Dynamic monitoring of plasma Epstein-Barr Virus DNA load can predict the occurrence of lymphoproliferative disorders after haploidentical hematopoietic stem cell transplantation

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.

The value of 18 F-FDG PET/CT quantitative indexes in the diagnosis of nondestructive posttransplant lymphoproliferative disorders after pediatric liver transplantation.

Posttransplant lymphoproliferative disease (PTLD) is a serious complication after pediatric liver transplantation (pLT), which may lead to death. 18 F-FDG PET/CT is rarely considered in PTLD after pLT and lacks clear diagnostic guidelines, especially in the differential diagnosis of nondestructive PTLD. The aim of this study was to find a quantifiable 18 F-FDG PET/CT index to identify nondestructive PTLD after pLT. This retrospective study collected the data of patients who underwent pLT, postoperative lymph node biopsy, and 18 F-FDG PET/CT at Tianjin First Central Hospital from January 2014 to December 2021. Quantitative indexes were established using lymph node morphology and the maximum standardized uptake value (SUVmax). A total of 83 patients met the inclusion criteria and were included in this retrospective study. To distinguish between PTLD-negative cases and nondestructive PTLD cases, according to the receiver operating characteristic curve, (the shortest diameter of the lymph node at the biopsy site [SDL]/the longest diameter of the lymph node at the biopsy site [LDL])*(SUVmax at the biopsy site [SUVmaxBio]/SUVmax of the tonsils [SUVmaxTon]) had the maximum area under the curve (0.923; 95% confidence interval: 0.834-1.000), and the cutoff value was 0.264 according to the maximum value of Youden's index. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 93.6%, 94.7%, 97.8%, 85.7%, and 93.9%, respectively. (SDL/LDL)*(SUVmaxBio/SUVmaxTon) has good sensitivity, specificity, positive predictive and negative predictive values, and accuracy, and can be used as a good quantitative index for the diagnosis of nondestructive PTLD.

Post-transplant lymphoproliferative disease after pediatric kidney transplant.

Post-transplant lymphoproliferative disease (PTLD) is the most common malignancy complicating solid organ transplantation (SOT) in adults and children. PTLD encompasses a spectrum of histopathologic features and organ involvement, ranging from benign lymphoproliferation and infectious-mononucleosis like presentation to invasive neoplastic processes such as classical Hodgkin lymphoma. The predominant risk factors for PTLD are Epstein-Barr virus (EBV) serostatus at the time of transplant and the intensity of immunosuppression following transplantation; with EBV-negative recipients of EBV-positive donor organs at the highest risk. In children, PTLD commonly presents in the first two years after transplant, with 80% of cases in the first year, and over 90% of cases associated with EBV-positive B-cell proliferation. Though pediatric kidney transplant recipients are at lower risk (1-3%) for PTLD compared to their other SOT counterparts, there is still a significant risk of morbidity, allograft failure, and an estimated 5-year mortality rate of up to 50%. In spite of this, there is no consensus for monitoring of at-risk patients or optimal management strategies for pediatric patients with PTLD. Here we review pathogenesis and risk factors for the development of PTLD, with current practices for prevention, diagnosis, and management of PTLD in pediatric kidney transplant recipients. We also highlight emerging concepts, current research gaps and potential future developments to improve clinical outcomes and longevity in these patients.

EPSTEIN-BARR VIRUS POSITIVE (EBV+) ORAL ULCER IN PATIENT WITH POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER

A 55-year-old male patient, after hematopoietic stem cell transplantation (HSCT) due to myelodysplastic syndrome, presented plaques not resistant to scraping in the lingual ventral surface region 65 days after HSCT that were suggestive of oral candidiasis, for which he was prescribed topical antifungal and therapeutic dose of fluconazole. After 5 days, the patient developed cervical lymph node enlargement, increased oral plaques, and multiple oral ulcers. Both lymph nodes and oral lesions were Epstein-Barr virus (EBV)-positive, which contributed to the diagnosis of posttransplant lymphoproliferative disease (PTLD). The first-choice treatment was rituximab, which was started immediately. Symptomatic control and photodynamic therapy for oral ulcers were performed. After 2 months of follow-up, the lesions in the oral cavity improved, but the clinical condition worsened, and the patient died. Mucocutaneous ulcer EBV-positive is a clinical entity recently described in immunosuppressed patients that can assist in the diagnosis and institution of appropriate treatment for PTLD.

P1339: CLINICAL OUTCOMES OF PATIENTS WITH EBV+ PTLD FOLLOWING HEMATOPOIETIC STEM CELL TRANSPLANTATION WHO FAIL RITUXIMAB: A MULTINATIONAL, RETROSPECTIVE CHART REVIEW STUDY

Background: Post-transplant lymphoproliferative disease (PTLD) occurs following allogeneic hematopoietic stem cell transplantation (HCT) as a consequence of immunosuppression. In most cases following HCT, PTLD is associated with Epstein-Barr Virus (EBV) infection of B cells, either due to reactivation, or from primary EBV infection (Styczynski J, Haematol. 2016; Allen UD, Am J Transplant, 2019; Nijand M, Transplant Direct, 2016). Clinical practice treatment guidelines recommend rituximab as preemptive therapy for EBV reactivation (based on EBV virus load) and for treatment of EBV-driven (EBV+) PTLD following HCT. However, EBV+ PTLD patients (pts) who fail rituximab have very poor outcomes with limited treatment options. Published evidence on the clinical outcomes of these pts who fail rituximab is also limited. Aims: To describe the outcomes for pts diagnosed with EBV+ PTLD following HCT who fail rituximab in a multinational real-world setting. Methods: We conducted a large multinational, multicenter retrospective chart review study of EBV+ PTLD pts following HCT or solid organ transplantation who received rituximab or rituximab plus chemotherapy (CT) between January 2000-December 2018 and were refractory (failed to achieve complete response [CR] or partial response [PR]) or relapsed at any point after such therapy. Data was collected from 29 centers across North America (United States and Canada) and the European Union. This analysis includes pts with EBV+ PTLD following HCT who were refractory or relapsed after rituximab ± CT as first line of therapy. The Kaplan-Meier (KM) method was used to estimate the overall survival (OS). Rituximab failure date was defined as the earliest date when pts became refractory or relapsed following rituximab ± CT. Results:: A total of 81 pts with EBV+ PTLD following HCT who failed rituximab ± CT were included in the analysis. Median age at PTLD diagnosis was 49 years (interquartile range [IQR]: 33‒57) and median time to PTLD onset from transplant was 3 months (IQR: 1.9‒4.2). Median follow-up time was 1.7 months (IQR: 0.6‒3.4) from the date of PTLD diagnosis. Of all the PTLDs, 52 (64.2%) were monomorphic, 18 (22.2%) polymorphic, 2 (2.5%) early lesions, and 9 (11.1%) were unknown. The most common PTLD subtype was diffuse large B-cell lymphoma (DLBCL) (46, 56.8%). Sixty-eight (84%) pts received rituximab monotherapy and 13 (16%) pts received rituximab plus CT as first line of therapy. Seven out of 13 pts who received rituximab plus CT had received preemptive rituximab treatment for EBV viremia prior to PTLD treatment. Median OS was 0.7 months (95% CI: 0.3‒1; IQR: 0.1‒2.7) for 81 pts from rituximab failure date (Figure 1). Median OS from PTLD diagnosis was 1.7 months (95% CI: 1.1‒2.3; IQR: 0.6‒3.4). Seventy-four (91.4%) out of the 81 pts ultimately died. Causes of death comprised 50 (67.6%) related to PTLD and therapy, 10 (13.5%) graft-versus-host disease (GvHD), 5 (6.8%) from sepsis/infection, 3 (4.1%) due to primary disease leading to HCT, 2 (2.7%) organ failure, 1 (1.4%) graft failure, 1 (1.4%) from hepatic failure, and 2 (2.7%) unknown. Image:Summary/Conclusion: The prognosis of EBV+ PTLD pts following HCT who fail rituximab ± CT remains very poor with an estimated median OS of less than 1 month, highlighting the significant unmet need in this population.

Intravenous Immunoglobulin G (IVIg) and Ganciclovir or Valganciclovir for the Treatment of Ebstein Barr Virus (EBV) Viremia and Prevention of Post-Transplant Lymphoproliferative Disease (PTLD) in Pediatric Heart Transplant Recipients

<h3>Purpose</h3> EBV viremia can progress to a potentially fatal PTLD. Data on the use of IVIg and antiviral agents such as ganciclovir or valganciclovir for the treatment (Rx) of this condition are limited. This study retrospectively evaluated the efficacy of IVIg with the combination of antiviral therapy in reducing EBV viral load and preventing PTLD in pediatric heart transplant patients (pts). <h3>Methods</h3> All pts transplanted since December 2007 were included. IVIg plus antiviral was implemented as empiric Rx in clinically significant EBV viremia polymerase chain reaction (PCR) > 100,000 copies/mL). Pts who were refractory to this tx and had EBV PCR > 250,000 copies/mL received rituximab. The pts were divided into two groups, those that received empiric Rx and those that did not. Pts who did not receive empiric Rx never had EBV viremia or only had EBV viremia at the time of PTLD diagnosis. The change from baseline EBV PCR values over time was evaluated, and the actuarial freedom from PTLD was compared between the two groups. <h3>Results</h3> There were 88 pts in the non-Rx group and 18 pts in the empiric Rx group. In the empiric Rx group, 9 pts received rituximab. The median time of initial EBV viremia incident was 27.7 months after transplantation. Pts on empiric Rx experienced an initial decrease in EBV viral load (p = 0.009) and maintain an acceptable EBV PCR level compared to baseline. None of the treated pts, including those who were refractory, developed PTLD. In the non-Rx group, 5 pts developed PTLD (p = 0.272). <h3>Conclusion</h3> A clinically important finding was observed when EBV viremia was identified with steps implemented to minimize viral load by utilizing IVIg, antivirals, and rituximab. It appeared that PTLD may be avoided though our data did not yet reach statistical significance. A large prospective clinical trial is indicated to support the use of this empiric Rx for the prevention of PTLD.

Clinical Outcomes of Patients with Epstein-Barr Virus-Driven Post-Transplant Lymphoproliferative Disease Following Hematopoietic Stem Cell Transplantation Who Fail Rituximab: A Multinational, Retrospective Chart Review Study

Background: Post-transplant lymphoproliferative disease (PTLD) occurs following allogeneic hematopoietic stem cell transplantation (HCT) as a consequence of immunosuppression. In most cases following HCT, PTLD is associated with Epstein-Barr Virus (EBV) infection of B cells, either due to reactivation, or from primary EBV infection (Styczynski J, Haematol. 2016; Allen UD, Am J Transplant, 2019; Nijand M, Transplant Direct, 2016). Clinical practice treatment guidelines recommend rituximab as preemptive therapy for EBV reactivation (based on EBV virus load) and for treatment of EBV-driven (EBV +) PTLD following HCT. However, EBV + PTLD patients (pts) who fail rituximab have very poor outcomes with limited treatment options. There are ongoing clinical studies investigating innovative therapies to address unmet needs in these pts. Published evidence on the clinical outcomes of these pts who fail rituximab is also limited. We aimed to describe the outcomes for pts diagnosed with EBV + PTLD following HCT who fail rituximab in a multinational real-world setting.Methods: We conducted a large multinational, multicenter retrospective chart review study of EBV + PTLD pts following HCT or solid organ transplantation who received rituximab or rituximab plus chemotherapy (CT) between January 2000-December 2018 and were refractory (failed to achieve complete response [CR] or partial response [PR]) or relapsed at any point after such therapy. Treatment response was assessed by either clinical diagnosis, radiographic/imaging, biopsy/cytology, or a combination of such assessments. Data was collected from 29 centers across North America (United States and Canada) and the European Union. The study population was aligned with the ongoing investigational trial (Clinicaltrials.gov Identifier: NCT03394365). This analysis includes pts with EBV + PTLD following HCT who were refractory or relapsed after rituximab ± CT as first line of therapy. The Kaplan-Meier (KM) method was used to estimate the overall survival (OS). Rituximab failure date was defined as the earliest date when pts became refractory or relapsed following rituximab ± CT.Results: A total of 81 pts with EBV + PTLD following HCT who failed rituximab ± CT were included in the analysis. Median age at PTLD diagnosis was 49 years (interquartile range [IQR]: 33‒57) and median time to PTLD onset from transplant was 3 months (IQR: 1.9‒4.2). Median follow-up time was 1.7 months (IQR: 0.6‒3.4) from the date of PTLD diagnosis. Of all the PTLDs, 52 (64.2%) were monomorphic, 18 (22.2%) polymorphic, 2 (2.5%) early lesions, and 9 (11.1%) were unknown. The most common PTLD subtype was diffuse large B-cell lymphoma (DLBCL) (46, 56.8%).Sixty-eight (84%) pts received rituximab monotherapy and 13 (16%) pts received rituximab plus CT as first line of therapy. Seven out of 13 pts who received rituximab plus CT had received preemptive rituximab treatment for EBV viremia prior to PTLD treatment. Median OS was 0.7 months (95% CI: 0.3‒1; IQR: 0.1‒2.7) for 81 pts who failed first line rituximab ± CT (Figure 1). Median OS from PTLD diagnosis was 1.7 months (95% CI: 1.1‒2.3; IQR: 0.6‒3.4).Seventy-four (91.4%) out of the 81 pts ultimately died. Causes of death comprised 50 (67.6%) related to PTLD and therapy, 10 (13.5%) graft-versus-host disease (GvHD), 5 (6.8%) from sepsis/infection, 3 (4.1%) due to primary disease leading to HCT, 2 (2.7%) organ failure, 1 (1.4%) graft failure, 1 (1.4%) from hepatic failure, and 2 (2.7%) unknown.Conclusions: The prognosis of EBV + PTLD pts following HCT who fail rituximab ± CT remains very poor with an estimated median OS of less than 1 month, highlighting the significant unmet need in this population. [Display omitted] DisclosuresStorek: Atara Biotherapeutics: Other: Site PI, Research Funding. Socié: Alexion: Research Funding. Thirumalai: Atara Biotherapeutics: Current Employment. Guzman-Becerra: Atara Biotherapeutics: Current Employment. Xun: Atara Biotherapeutics: Current Employment. Kumar: Roche: Research Funding; GSK: Research Funding; Amplyx: Research Funding; Merck: Research Funding; Takeda & Atara: Research Funding. Sadetsky: Atara Biotherapeutics: Current Employment. Dierickx: Sandoz: Consultancy; Sanofi: Consultancy; Novartis: Consultancy; Roche: Consultancy, Research Funding; Takeda, Incyte, Atara: Consultancy. Reitan: Atara, Kite, Janssen: Research Funding. Barlev: Atara Biotherapeutics: Current Employment. Mohty: Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria.

Incidence and Outcomes of Post-Transplant Lymphoproliferative Disease after 5365 Solid Organ Transplants over a 20 Year Period at 2 UK Transplant Centres

Background:Post-transplant lymphoproliferative disease (PTLD) confers a high morbidity and mortality in a vulnerable population. We present the epidemiology and outcomes of PTLD in a large UK cohort of solid organ transplant (SOT) recipients who were transplanted over a 20-year period.Methods:This is a retrospective study of 5365 SOT recipients who had their first transplant between 2000 and 2021 at two UK transplant centres (Addenbrooke's Hospital and Papworth Hospital). We reviewed the records of all patients and found 142 who subsequently developed PTLD. For each type of transplant, we calculated the incidence rate of PTLD and cumulative incidence using a competing risk of death model.Survival was compared with the age-adjusted life expectancy of the UK population using the National life tables and a landmark analysis was performed to compare overall survival (OS) of PTLD patients from the date of diagnosis with the background survival of the transplant population. To compare treatment outcomes, a subset of 90 cases of monomorphic PTLD, DLBCL subtype were identified. 66 were treated with first-line Rituximab monotherapy and 24 received first-line R-Chemotherapy. Demographics, treatment response, and survival data were analysed with univariate and multivariate analysis to identify covariates associated with death in the first year post diagnosis of PTLD.Results:With a median follow-up time of 5.3 years, 142 of 5365 solid organ transplant recipients have developed PTLD (56/1965 kidney, 22/1428 liver, 12/327 simultaneous kidney-pancreas (SPK), 21/113 multivisceral (MVT), 10/778 heart, 15/503 bilateral lung, 3/148 single lung and 3/85 heart and lung). The incidence rate of PTLD was highest in the first year post-transplant in lung and MVT recipients. Cumulative incidence (shown in Figure 1) was 18% at 5 years post-MVT and 1-3% at 5 years following the other SOT types. Cumulative incidence was lowest for liver and heart transplants and was 10% at 20 years post-kidney transplantation.Median OS following SOT was 16 years which is significantly reduced compared with the age-adjusted UK population. There is a relatively high early mortality rate following diagnosis of PTLD and only patients surviving two years post diagnosis regained a similar longer-term survival to the non-PTLD SOT cohort.Treatment with rituximab monotherapy (RM) is now a standard of care for monomorphic PTLD 1. Outcomes for monomorphic patients were compared between those treated with RM (n=66, median follow-up 2.2 y) and R-Chemotherapy (n=24, median follow-up 5.2 y). The two groups were well matched for age and IPI. Of the 66 RM patients, 22 (33%) achieved complete remission with RM and required no further treatment. A further 18 (27%) patients achieved remission following further treatment with chemotherapy/surgery/CTL. 6/66 (9%) patients died of progressive disease (PD), 9/66 (14%) died pre-remission of non-PTLD causes and 11/66 (17%) died in remission of unrelated causes. In the R-Chemotherapy group, 22 patients received R-CHOP and 2 received R-CVP (n=24). 8 (33%) patients are alive and in remission after first line treatment and a further 3 patients (13%) after second line treatment. 2/24 (8%) patients died of PD, 4/24 (17%) died pre-remission of non-PTLD causes and 7/24 (30%) died post-remission of unrelated causes. There is no significant difference in OS between the two groups. Only a minority of deaths were due to PD and death from non-lymphoma causes pre and post remission remain considerably higher than non-PTLD SOT patients up to 2 years post treatment (Figure 1). Multivariate analysis of all 90 monomorphic PTLD patients identified IPI3+ as the strongest pre-treatment variable associating with inferior 1 year OS. Interestingly IPI3+ did not retain this significance when R-chemo patients were analysed alone.Conclusion:With this large SOT dataset we have mapped the cumulative incidence of PTLD over a 20 year period and highlight transplanted organ-specific differences in PTLD incidence over time. Treating monomorphic DLBL patients first-line with RM rather than R-chemotherapy does not appear to compromise OS, but the number of patients dying from non-lymphoma causes pre- and post-treatment remains high with both treatment approaches, with poor OS compared with age-matched non-PTLD SOT recipients.1Trappe et al. Lancet Oncol; 2012 13(2):196-206 [Display omitted] DisclosuresSantarsieri: Janssen: Honoraria. Uttenthal: Roche: Other; Takeda: Other; Jazz: Other. Follows: Janssen, Abvie, Roche, AZ: Other.

Survival of Post-Transplant Lymphoproliferative Disorder after Kidney Transplantation in Patients under Rapamycin Treatment.

Background: One of the important causes of mortality and morbidity in kidney transplanted patients is Post Transplant Lymphoproliferative Disease (PTLD), which is due to immunosuppression therapy and viral activity. It seems that Rapamycin, with dual antineoplastic and immunosuppressive effects, may have a pivotal role in the treatment of PTLD patients and preserving transplanted kidneys. Methods and Materials: Twenty patients with PTLD were enrolled. Immunosuppressive therapy was reduced or ceased, and Rapamycin was initiated at the time of PTLD diagnosis. We evaluated the effects of switching immunosuppressive drugs to Rapamycin on graft status, the response of tumor, and 6, 12 months, and 5-year survival in patients. Results: PTLD remission was achieved in 14 patients, while six patients died; no relapse was detected in recovered patients. The median of PTLD free time was 25 months, and the mean overall survival in patients with PTLD treated by Rapamycin was 84.8 (95% CI=61.3-108.23).The five-year survival rate was 67%, 12 months survival was 73.8%, and six months' survival was 80%. The response rate to Rapamycin and immunosuppression reduction alone was 46.6%. Four out of 13 Diffuse Large B-Cell Lymphoma patients achieved a complete response just only after the reduction of immunosuppressive drugs and the consumption of Rapamycin. Conclusion: The present study demonstrated the effectiveness of conversion from immunosuppressive medication, particularly of Calcineurin inhibitors to Rapamycin in PTLD patients. However, more research is needed to confirm the Rapamycin effect on patients with PTLD.

Course of renal allograft function after diagnosis and treatment of post-transplant lymphoproliferative disorders in pediatric kidney transplant recipients.

Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication in renal transplant recipients. Immunomodulatory and chemotherapeutic treatment potentially affect allograft function. The aim of this study was to evaluate graft function of pediatric kidney transplant recipients following diagnosis and standardized treatment of PTLD. Patients were identified from the German Ped-PTLD registry, and data on renal function were retrospectively retrieved from patient charts. For PTLD treatment, immunosuppressive therapy was reduced and all children received rituximab (375mg/m2 ) for up to six doses. Two patients required additional low-dose chemotherapy. Renal allograft function was monitored by consecutive measurements of estimated glomerular filtration rate (eGFR) at defined time points. Follow-up was up to 60months after PTLD. Twenty patients were included in this cohort analysis. Median time from transplantation to PTLD was 2.4years. Histopathology showed monomorphic lesions in 16 and polymorphic in 4 patients. Two patients experienced PTLD relapse after 2 and 14months. Range-based analysis of variance showed stable allograft function in 17 of 20 patients (85%). Mean eGFR increased during early treatment phase. One patient experienced graft rejection 5.3years after diagnosis of PTLD. Another patient developed recurrence of primary renal disease (focal-segmental glomerulosclerosis) and lost his renal allograft 3.8years post-transplant (2.0years after PTLD diagnosis). Treatment of PTLD with rituximab with or without low-dose chemotherapy in combination with reduced immunosuppression, mostly comprising of an mTOR inhibitor-based, calcineurin inhibitor-free regimen, is associated with stable graft function and favorable graft survival in pediatric renal transplant patients.

Cost burden of post-transplant lymphoproliferative disease following kidney transplants in Medicare-eligible patients by survival status

Aims and Objectives Patients diagnosed with post-transplant lymphoproliferative disease (PTLD) experience high mortality within the first 2 years of diagnosis; however, few data exist on the economic burden of PTLD in these patients. We determined the healthcare resource utilization (HRU) and cost burden of post-kidney transplant PTLD and evaluated how these differ by survival status. Materials and Methods Utilizing data from the United States Renal Data System and the Scientific Registry of Transplant Recipients, we identified 83,818 Medicare-covered kidney transplant recipients between 2007 and 2016, of which 347 had at least one Medicare claim during the first year after diagnosis of PTLD. We tabulated Medicare Part A and Part B and calculated per patient-year (PPY) costs. Results Patients diagnosed with PTLD in the first year post-transplant had Part A + B costs of $222,336 PPY, in contrast with $83,546 PPY in all kidney transplants. Post-transplant costs in the first year of PTLD diagnosis were similar regardless of the year of diagnosis. Cost burden for PTLD patients who died within 2 years of diagnosis was >3.3 times higher than PTLD patients still alive after 2 years. Of those who died within 2 years, the majority died within 6 months and costs were highest for these patients, with almost 7 times higher costs than PTLD patients who were still alive after 2 years. Limitations Medicare costs were the only costs examined in this study and may not be representative of other costs incurred, nor be generalizable to other insured populations. Patients were only Medicare eligible for 3 years after transplant unless aged ≥62 years, therefore any costs after this cut-off were not included. Conclusions PTLD represents a considerable HRU and cost burden following kidney transplant, and the burden is most pronounced in patients who die within 6 months.

Epstein-Barr Virus-Associated Post-transplant Lymphoproliferative Disease.

Epstein-Barr virus (EBV) is associated with a variety of malignancies including post-transplant lymphoproliferative disease (PTLD). These include B and T cell lymphomas, epithelial, and mesenchymal tumors. The virus is ubiquitous, transmitted in saliva, and not usually associated with the development of malignancy. PTLD is usually associated with EBV when it occurs soon after the transplant. Measurement of viral DNA in blood, especially plasma, may be useful in the diagnosis of PTLD. Treatment approaches include withdrawal of immunosuppression, monoclonal antibodies or antibody conjugates, cytotoxic chemotherapy, and a variety of virus-specific treatments such as adoptive cellular therapy with EBV-specific T cells. Approaches to prevention include selection of immunosuppressive regimens that minimize the risk. In the future, EBV vaccines may be available for potential transplant recipients.

High Healthcare Resource Utilization and Cost for PTLD Patients Following Kidney Transplants

Background: Post-transplant lymphoproliferative disease (PTLD) is a rare and aggressive disease with high mortality rates, and may have substantial healthcare resource utilization (HRU) and cost. Objectives: To describe the HRU and Medicare paid amounts up to 3 years after kidney transplants for PTLD patients and for all kidney transplant patients. Methods: The United States Renal Data System (USRDS) is a national data system that collects, analyzes and distributes information about chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the United States. It is a claim dataset that provides Medicare paid amounts and HRU for these patients, including their kidney transplants. Patients are Medicare-eligible for 3 years after a successful kidney transplant. The Scientific Registry of Transplant Recipients (SRTR) is a national data system that reports data from transplant centers on all solid organ transplants in the US, including data on malignancies after transplants, including PTLD. The USRDS data was used to identify Medicare-covered kidney transplant recipients from 2007 until 2016. SRTR malignancy data were used to obtain patients with a PTLD diagnosis, which was linked to the USRDS. Patients had to have a USRDS claim on the date of transplantation. Only patients enrolled in Medicare Part A and Part B fee-for-service were included. Solitary kidney re-transplants were included but not multi-organ transplants, due to a potential difference in HRU and cost in the latter. Medicare Part A (inpatient, outpatient, home health, hospice, skilled nursing) and B HRU and paid amounts were tabulated for up to 3 years' post-transplant. The year post-transplant was calculated using 365.25 days per year following the kidney transplant. For example, recipients with a PTLD diagnosis any time within 365.25 days following their kidney transplant were considered a PTLD patients within 1-year post-transplant. A per person-year (PPY) was computed to standardize costs. Patients were censored at loss of Medicare eligibility or death or at the end of 3-year post-transplant. Results: A total of 83,818 Medicare-covered kidney transplants were included in this study with a mean age of 51.55 (SD: 15.11) at transplant and 60.77% male. Average paid amount from transplant to 1-year post-transplant was $83,546 PPY, with approximately two-thirds of the cost coming from inpatient hospitalization. For year 2 and 3 post-transplant, the average paid amount was $26,148 PPY and $25,326 PPY, respectively, with similar cost coming from inpatient and Part B (~39% each). Among these kidney transplant recipients, 281 transplant recipients had PTLD while Medicare-eligible with an average age of 53.98 (SD: 19.19) years at transplant and 67.97% male. Median time from transplant to PTLD diagnosis was 1.02 years (IQR: 0.60-1.93 years). For patients who were diagnosed with PTLD within the first year after transplant (n=139), average paid amount from date of the first PTLD diagnosis to 1-year post-transplant was $222,336 PPY, with approximately two-thirds of the cost from inpatient hospitalization. Of these patients who survived or were eligible in year 2 (n=94) and 3 (n=64), the average cost was $60,981 PPY and $36,118 PPY, respectively. For patients who were diagnosed with PTLD in the second year after transplant (n=81), average paid amount in year 2 post-transplant was $203,374 PPY with approximately 60% coming from inpatient hospitalization. Year 3 post-transplant cost for these PTLD patients who survived or were eligible (n=59) was $58,879 PPY. For patients who were diagnosed with PTLD in the third year after transplant (n=61), average paid amount in year 3 post-transplant was $211,941 PPY with 68% coming from inpatient hospitalization. Conclusions: PTLD is associated with substantial HRU and cost (&amp;gt;$200k PPY in the year diagnosed), regardless of the year diagnosed post-transplant, while patients without PTLD and patients who haven't developed PTLD yet had a cost of ~$83k PPY in year 1, and ~$26k PPY for year 2 and 3 post-transplant. Disclosures Ahn: Medtronic: Current equity holder in publicly-traded company; Bristol-Myers Squibb: Research Funding. Watson:Atara Biotherapeutics: Current Employment, Current equity holder in publicly-traded company. Skeans:Bristol-Myers Squibb: Research Funding; Astellas: Research Funding; Atara Biotherapeutics: Research Funding. Barlev:Atara Biotherapeutics: Current Employment, Current equity holder in publicly-traded company. Thompson:Atara Biotherapeutics: Research Funding; Bristol-Myers Squibb: Research Funding. Dharnidharka:Atara Biotherapeutics: Consultancy, Honoraria, Research Funding; CareDx: Honoraria, Research Funding, Speakers Bureau.

Post-Transplant Lymphoproliferative Disorder after Solid Organ Transplant in the Pediatric Population: A Systematic Review

Background: Post-transplant lymphoproliferative disease (PTLD), is one of the major complications after organ transplantation. The aim of this study is to study the incidence, risk factors especially EBV status, histopathological types, management, and outcomes of PTLD in the pediatric groups. Methods: Following the PRISMA guideline, we performed a comprehensive literature search on PubMed, Cochrane Library, Embase, and clinicaltrials.gov from the past ten years on May 04, 2020. We used the MeSH terms of organ transplantation and lymphoproliferative disorders. The initial search revealed 1741 articles. We excluded all case reports, case series, pre-clinical trials, review articles, and meta-analysis. We found twenty-eight studies. We extracted the data for baseline characteristics, recipient &amp; donor EBV status, immunosuppression used, type &amp; stage of PTLD, organ system involved, duration between transplant and PTLD diagnosis, treatment, and mortality. Results: We included 32 studies with a total (n) of 15597 pediatric patients after a solid organ transplant. 1210 (7.75%) patients developed PTLD, out of which 609 (50.33%) were male participants, 453 (37.4%) female, and 148 (12.23%) the gender was unknown. (Table 1) Data from 19 studies showed that among PTLD patients, 115 recipients &amp; 76 donors tested positive for Epstein-Barr Virus (EBV), 187 recipients were seronegative and the rest were unknown at the time of transplant. Immunosuppressive drugs used after organ transplantation included; cyclosporine, tacrolimus, sirolimus, azathioprine, mycophenolate, prednisone, mTOR inhibitors, induction therapy with OKT3, IL-2 inhibitors (basiliximab, daclizumab) and anti-thymocyte/anti-lymphocyte globulin. In two studies, antiviral prophylaxis with ganciclovir/valganciclovir was achieved. Data from nine studies showed the median age at PTLD diagnosis was 6.8 years. L'Huillier et al. stated that the median duration for EBV positive recipients to develop PTLD was 1.92 years (0.35-3.09 years), compared to EBV negative recipients, which was 0.95 years (2.48-2.92 years). Overall, the median duration from organ transplant to the diagnosis of PTLD among 15 studies was 29.1 months, ranging from 0.9 months to 186 months. The histopathology of PTLD was confirmed via biopsy specimen showing predominance in monomorphic type, i.e; 265/1210 (21.9%), followed by polymorphic type with 140/1210 (11.5%), an early lesion with 46/1210 (3.80%), Non-Hodgkin lymphoma 28/1210 (2.3%), Hodgkin lymphoma 33/1210 (2.72%) and mixed type (polymorphic &amp; monomorphic) 4/1210 (0.33%). Histopathological data for 694 patients were not available. Treatment of PTLD was achieved with reduction or complete cessation of immunosuppressive therapy, anti-CD20 antibody (rituximab), antiviral treatment with ganciclovir/valganciclovir, lymphoma treatment with chemotherapeutic agents, radiotherapy, and surgical resection. Gajarski et al. concluded that patients who received induction therapy [OKT3, IL-2 antagonists (basiliximab, daclizumab) and anti-thymocyte globulin] had significantly less PTLD development as compared to those who did not receive induction therapy, i.e., (2.9% vs. 4.9%) among 2374 total patients. According to Hayes Jr. et al., recipient EBV seronegativity continued to be associated with lower mortality hazard (HR 0.715; 95 % CI 0.547, 0.935; p = 0.014). Data from 19 studies showed the mortality rate among 494 PTLD diagnosed patients was 22.7% (112) with an overall survival of 84.2% respectively from three studies. Data from five studies showed that direct PTLD related mortality accounted for 63% (17/27) of deaths in PTLD diagnosed patients. Conclusion: Our analysis shows that post-transplant EBV positive recipients who undergo multiorgan transplants are more likely to develop PTLD compared to EBV positive recipients with single organ transplantation. The median duration from organ transplants to the diagnosis of PTLD ranged from months to years, however, this duration was reported to be less in EBV negative recipients compared to EBV positive recipients with organ transplants. The most common histological type of PTLD among pediatric groups was monomorphic and the least common was Classic Hodgkin lymphoma. Rituximab use in the treatment of PTLD was associated with a decreased use of alkylating agents and as a result, the side effects associated with these agents were reduced. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Post-Transplant Lymphoproliferative Disorder after Liver Transplant in the Pediatric Population: A Systematic Review

Background: Post-transplant lymphoproliferative disease (PTLD), a group of lymphoid disorders ranging from indolent polyclonal proliferation to aggressive lymphomas is a known complication following solid organ transplantation. The aim is to study the characteristics, predictive factors, management, and outcomes of PTLD among pediatric groups after liver transplantation in particular. Methods: Following the PRISMA guideline, we performed a comprehensive literature search on PubMed, Cochrane Library, Embase, and clinicaltrials.gov from the past ten years on May 04, 2020. We used the MeSH terms of organ transplantation and lymphoproliferative disorders. Initial search revealed 1741 articles. We excluded all case reports, case series, pre-clinical trials, review articles, and meta-analysis. We found five retrospectives observational, one observational cohort study, and one multicenter cohort in the pediatric population. We extracted the data for baseline characteristics, the reason for transplantation, recipient &amp; donor EBV status, immunosuppression used, type &amp; stage of PTLD, organ system involved, duration between transplant and PTLD diagnosis, treatment, response to therapy, adverse effects of therapy and mortality. Results: We included seven retrospective observational studies with a total (n) number of 3116 post-liver transplant pediatric patients, out of which 135 (4.33%) patients who developed PTLD as a complication of transplantation were studied. The male to female ratio was 41: 55 with the gender of 6 patients unknown. In five studies, with 118 PTLD patients, 34 recipients and 24 donors were positive for EBV at the time of liver transplantation. In addition to EBV, CMV status of patients in 5 studies showed 11/25 (44%) PTLD patients positive for CMV at the time of transplant. Post-transplant immunosuppression was achieved among these seven cohorts with cyclosporine, tacrolimus, OKT3, mycophenolate mofetil, prednisone, and basiliximab. The diagnosis was made via biopsy, showing all histopathological types including early lesions 14/46 (30.4%), polymorphic 13/46 (28.3%), monomorphic 18/46 (39.1%), and classic Hodgkin's lymphoma PTLD 1/46 (2.1%). Diffuse large B-cell lymphoma was the most common subtype in 6/18 (33.3%) of samples with monomorphic PTLD. Hsu, et al. in their study showed a five-year survival rate of 33.3% for St. Jude's classification stage IV lymphoma compared to 88.9% for stage I-III. The median age for 36 patients from three studies at the diagnosis of PTLD was 39.6 months (range 24-48 months). The median duration from transplantation to the diagnosis of PTLD was 13.48 months (range 8-24 months) in 54 patients from four studies. PTLD treatment was achieved with a combination of reduction or withdrawal of the immunosuppressive drugs with antiviral prophylaxis, chemotherapy, irradiation &amp; the use of monoclonal antibodies in a total of 57 PTLD patients for which post-transplant immunosuppression data was available. Study by Hsu, et al. reported that 5/16 (31.3%) patients had acute graft rejection and 2 had a chronic rejection in a group of 16 PTLD patients undergoing treatment for PTLD with a reduction in immunosuppressive therapy. The overall mortality in patients who developed PTLD was 15/54 (27.8%) in four of the studies. Conclusions: Pre-transplant EBV-naive status in patients was associated with a higher incidence of PTLD. Advanced stage (Stage IV) lymphoma was associated with poor survival outcomes. Monomorphic histopathology may be most commonly associated with PTLD post-liver transplant. The main approach for the treatment of PTLD is the reduction or complete withdrawal of immunosuppressive drugs, administration of antiviral drugs (ganciclovir/valganciclovir),and lymphoma treatment with chemotherapy or irradiation, and monoclonal antibody therapy such as rituximab. Management of PTLD with reduction or withdrawal of post-transplant immunosuppressive drugs in one cohort was associated with an increased risk of graft rejection. Thus immunosuppressive therapy maintaining a fine balance between the risk of graft rejection and risk of developing PTLD may be associated with better patient outcomes post-liver transplant. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Post-Transplant Lymphoproliferative Disorder after Renal Transplant in the Pediatric Population: A Systematic Review

Background: Post-transplant lymphoproliferative disease (PTLD), is one of the major complications after organ transplantation. The aim of this study is to study the incidence, various risk factors especially EBV status, histopathological types, management, and outcomes of PTLD following kidney transplantation in the pediatric groups. Methods: Following the PRISMA guideline, we performed a comprehensive literature search on PubMed, Cochrane Library, Embase, and clinicaltrials.gov from the past ten years on May 04, 2020. We used the MeSH terms of organ transplantation and lymphoproliferative disorders. The initial search revealed 1741 articles. We excluded all case reports, case series, pre-clinical trials, review articles, and meta-analysis. We found five retrospectives observational, one retrospective questionnaire survey, one prospective observational, and one prospective trial study. We extracted the data for baseline characteristics, the reason for transplantation, recipient &amp; donor EBV status, immunosuppression used, type &amp; stage of PTLD, organ system involved, duration between transplant and PTLD diagnosis, treatment, response to therapy, adverse effects of therapy and mortality. Results: We included eight studies with a total (n) number of 1713 post-kidney transplant pediatric patients, out of which 148 (8.63%) patients who developed PTLD as a complication of transplantation were studied(table 1). Among the 148 patients diagnosed with PTLD, 96 (64.86%) were males, 49 (33.1%) female participants and 3 (2.2%) were unknown. 34/148 (22.97%) PTLD recipients were EBV (+), 86 (58.1%) EBV (-) and 28 (18.9%) unknown at the time of transplant. EBV status for donors was known in only 2 studies, showing 7/99 (7.1%) to be EBV (+) at the time of transplant. Höcker et al. have shown that antiviral prophylaxis with ganciclovir/valganciclovir in the first year post-renal transplant reduces the risk of EBV viremia. Post-transplant immunosuppressive drugs included tacrolimus, mycophenolate mofetil, azathioprine, sirolimus, cyclosporine, IL-2R antagonist, methylprednisolone, basiliximab, daclizumab, anti-thymocyte globulin/anti-lymphocyte globulin, OKT3. In some cohorts, rituximab and antiviral prophylaxis with ganciclovir or valganciclovir were also used in some patients. The median time from transplant to the diagnosis of PTLD from five studies with 125 patients was 16 months (0.9m-186m). Longmore et al. reported a bimodal distribution curve, with 50% presenting with early PTLD, i.e. after a median duration of 313 days and 50% presenting late after a median duration of 8 years. The histopathological types of PTLD were diagnosed via biopsy samples, showing predominance with polymorphic type 48 (32.4%), followed by monomorphic type 45 (30.4%), early lesion 4 (2.7%), Kaposi like PTLD 1 (0.67%) and Hodgkin lymphoma 1 (0.67%). The histological testing results from two of the studies also showed that 18/19 (94.7%) of diagnosed PTLD samples were EBV positive. PTLD was managed with reduction or cessation of the immunosuppressive drugs, anti-CD20 antibodies, chemotherapy for lymphoma, and in some cases mTOR inhibitors, intravenous immunoglobulins, and surgical resection. Data from 5 studies show the mortality rate of 12/51 (23.5%) among PTLD groups. The survival rate from 2 studies was 100% among 17 PTLD patients and 1 study showed a 5-year survival rate of 85% among 92 PTLD patients. Cleper et al. in their study concluded that the type of PTLD might have a significant effect on the outcome, as ¾ (75%) deaths in the PTLD group were attributed to anaplastic T-cell type. Conclusions: Our analysis shows the EBV infection is closely associated with a higher risk of PTLD development. Recipients' EBV seronegativity and positive EBV status of the donor have been shown to increase post-transplant EBV infection risk which is associated with a higher risk of PTLD development. Furthermore, our study shows that PTLD may occur in less than a month to more than 15 years of renal transplant. The polymorphic type was the most common and Hodgkin lymphoma-type, the least commonly reported PTLD type. The main therapeutic approach is the reduction or cessation of immunosuppression. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Post-Transplant Lymphoproliferative Disorder after Liver Transplant: A Systematic Review

Background: Post-transplant lymphoproliferative disease (PTLD), a group of lymphoid disorders ranging from indolent polyclonal proliferation to aggressive lymphomas is a known complication following solid organ transplantation. The aim is to study the incidence, characteristics, predictive factors, management, and outcomes of PTLD after liver transplantation in particular. Methods: Following the PRISMA guideline, we performed a comprehensive literature search on PubMed, Cochrane Library, Embase, and clinicaltrials.gov from the past ten years on May 04, 2020. We used the MeSH terms of organ transplantation and lymphoproliferative disorders. The initial search revealed 1741 articles. We excluded all case reports, case series, pre-clinical trials, review articles, and meta-analysis. We found fifteen studies including retrospective observational and cohort studies. We extracted the data for baseline characteristics, the reason for transplantation, recipient &amp; donor EBV status, immunosuppression used, type &amp; stage of PTLD, organ system involved, duration between transplant and PTLD diagnosis, treatment, response to therapy, adverse effects of therapy and mortality. Results: We included 15 studies with a total (n) of 10706 post-liver transplant patients. 294 (2.74%) patients developed PTLD as a complication, out of which 104 (35.3%) were males, 106 (36%) females, and 84 unknowns. Table 1. The incidence of PTLD in the pediatric group was 135/3116 (4.3%) whereas in the adult population it was 115/7545 (1.5%). Data from eleven studies show that out of 202 participants, 67 recipients were positive, 39 negative, and 18 donors positive for EBV infection at the time of transplant. Data on the EBV serostatus for the remaining 106 recipients was not known at the time of transplant. Data from two studies showed that 25/29 patients who later developed PTLD were seronegative for EBV prior to the transplant and 26/29 were reported to undergo seroconversion partly due to transplantation with EBV positive donors (7/13). Post-transplant immunosuppression was achieved with cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, sirolimus, prednisone, OKT3 for acute cellular rejection and induction with monoclonal antibodies. Data from four studies conclude the median age at the time of PTLD diagnosis is 47.6 months in the pediatric population while 54 years in adults, overall ranging from 1 year to 73 years. Ten studies show the overall median duration from organ transplant to the diagnosis of PTLD is 23.5 months. The median duration for the pediatric population was 11.6 months from the data collected from 55 patients whereas five studies with 166 adult liver transplant recipients showed a median duration of 35.5 months. Histopathological types were diagnosed via biopsy samples, with monomorphic in 76 (25.8%), early lesions in 22 (7.4%), polymorphic in 19 (6.4%), and classic Hodgkin lymphoma like PTLD in 8 (2.7%) of the samples. Among the monomorphic type, Diffuse Large B-Cell Lymphoma (DLBCL) was the most commonly reported i.e. 10/50 (20%) of patients with monomorphic type in two studies. Treatment of PTLD consisted of reduction or cessation of the post-transplant immunosuppressive drugs, anti-CD20 antibody (rituximab), antiviral treatment with ganciclovir, and lymphoma treated with chemotherapy, radiotherapy, and surgical resection. Data from eight studies show a mortality rate of 61/214 (28.5%) with Huang, et al. reporting ¾(75%) of total deaths due to PTLD progression. Two studies report an overall survival rate of 26/32 (81.3%) and five-year survival of 15/41 (36.6%). Conclusions: Our analysis shows the incidence of PTLD after liver transplant is low with no significant gender predominance but a difference in the incidence was observed with significantly higher rates in the pediatric group as compared to the adult population. The most common biopsy proved histopathological type was monomorphic, with the least common type being Hodgkin lymphoma like PTLD. Among the monomorphic, DLBCL was the most common subtype. After liver transplantation, the development of PTLD is observed earlier in pediatric patients in comparison to adult recipients. EBV naive patients prior to liver transplantation are at higher risk for seroconversion post-transplant if transplanted with EBV positive donors and hence at increased risk of PTLD development. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

PRO33 COST BURDEN OF POST-TRANSPLANT LYMPHOPROLIFERATIVE DISEASE (PTLD) FOLLOWING KIDNEY TRANSPLANTS IN MEDICARE-ELIGIBLE PATIENTS BY SURVIVAL STATUS

Post-transplant lymphoproliferative disease (PTLD) is an ultra-rare disease that is a type of lymphoma following solid organ transplant. This study assessed cost burden of PTLD following kidney transplant, by survival status. Using United States Renal Data System data, we identified 2007-2016 Medicare-covered kidney transplant recipients who were diagnosed with PTLD. A per person per year (PPPY) Medicare cost was computed in the two years following PTLD diagnosis and stratified by survival status. Among the 83,828 Medicare-covered kidney transplant recipients, 364 (0.43%) patients with PTLD, while Medicare-eligible, were identified and analyzed. PTLD patients were 67% male, with an average age of 56 years at transplant (SD: 18 years), and age 58 years at PTLD diagnosis (SD: 19 years). Patients aged 0-17 years at transplant comprised of 6% of the PTLD population. Median time from transplant to PTLD diagnosis was 1.25 years (IQR: 0.67-2.70 years). A total of 222 patients (61%) were alive 2 years after PTLD diagnosis. Post-PTLD costs were $476K PPPY for those who died within 2 years of PTLD diagnosis and $78K PPPY for those who remained alive 2 years after PTLD, more than a 6-fold difference. The majority of post-PTLD costs were for inpatient stays: 69% among those who died within 2 years of PTLD diagnosis and 50% among those who remained alive. Of the patients who died within 2 years post-PTLD, 66% died within 6 months and costs were highest among these patients. Costs in PTLD patients following a kidney transplant are considerable. In the two year after PTLD diagnosis, the cost burden for PTLD patients who died within 2 years of diagnosis was over six times higher than PTLD patients who survived.