Basiliximab, a monoclonal antibody which targets activated T lymphocytes, was not related to PTLD risk in our study, as previously reported.4,27 Several studies have suggested that higher tacrolimus levels are associated with higher risk for PTLD, as well as others have reported that the net state of immunosuppression, rather Letermovir than any individual agent, increases the risk for PTLD.28,29,30 In our study, all patients received tacrolimus for maintenance immunosuppression, and we found that a higher pre-EV tacrolimus level in the PTLD group compared with the EV only group was a risk factor for PTLD. Regular monitoring of EBV viral load and early recognition of recipients at high risk of PTLD have been identified as clinical priorities in recent years.31 Previous studies have shown that elevated levels of EBV DNA and persistent high EBV loads are risk factors for PTLD,12,20,32 but no obvious cut-off point of EBV viral weight for the prediction of PTLD development has been determined. months); however, two experienced neutropenia and two developed infection requiring hospital admission. Conclusion In pediatric KT recipients, higher tacrolimus levels were associated with a higher incidence of PTLD. Conversely, those who received preemptive RTX for EV did not develop PTLD. mutation). After confirming that this patients did not have active contamination or neutropenia, a single dose of RTX therapy of 375 mg/m2 body surface area was administered. Statistical analysis To determine statistical differences between groups, we used the chi-square test or Fischer’s exact test for categorical variables and the value 0.2 for multivariate Cox regression analysis. Letermovir A value 0.05 was considered statistically significant. The statistical analysis was performed using IBM SPSS Statistics version 22.0 (IBM cooperation, Armonk, NY, USA). Ethics statement The study was approved by the Institutional Review Table (IRB) of our center (IRB No. H-1312-068-541). The informed consent requirement was waived by the board. RESULTS During the study period, 199 children underwent kidney transplantation in our center. Of these, 46 (23.1%) had viremia defined as an EBV weight greater than 1,000 copies/mL in whole blood for 2 consecutive assessments during a median follow-up period of 5.3 years (Fig. 1). Viremia of all patients (EBV 1,000 copies/mL) was first detected at a median of 6.7 months (range, 0.4C47.8 months) after kidney transplantation. The diagnosis of PTLD was made in seven patients (PTLD group) at a median of 8.2 months (2.8C98.9 months) after transplantation. The other 39 patients had EV only (EV only group). Open in a separate window Fig. 1 Distribution of patients with kidney transplantation by EBV status and PTLD.EBV = Epstein-Barr computer virus, PTLD = NES post-transplant lymphoproliferative disease, RTX = rituximab. Clinical course of PTLD Patients with PTLD presented with fever, lymph node enlargement, or gastrointestinal symptoms such as abdominal pain, vomiting, and diarrhea (Table 1). Any gastrointestinal symptoms and/or lymph node enlargement raised suspicion for PTLD and prompted the clinician to perform further work-up to rule out PTLD. The majority of patients (n = 4) experienced gastrointestinal organ involvement, including small bowel and intraperitoneal lymph nodes. There was no extranodal PTLD. Pathologic diagnosis of PTLD revealed one case of early lesion, two cases of polymorphic PTLD, one case of Burkitt lymphoma, and three cases of diffuse large B-cell lymphoma. Upon diagnosis of PTLD, immunosuppressive medications were reduced, and RTX and/or chemotherapy were administered as appropriate. All patients achieved total remission of PTLD after treatments. While one patient lost her allograft kidney due to complications of chemotherapy, six patients retained renal function after follow-up for 2.5C10.5 years. Table 1 Characteristics of patients with post-transplant lymphoproliferative disease mutation. Risk factors for PTLD Table 2 shows the comparison of clinical variables between the PTLD and EV only group by univariate analysis. There were no significant differences between the two groups in terms of sex, age at transplantation, donor type, interval between transplantation, and first appearance of EV. Even though peak median EBV titer was higher in the PTLD group (152,987 EBV copies/mL whole blood) than the EV only group (17,305 copies/mL whole blood), there was no statistical significance. There were also no significant differences between groups in terms of median EBV viral weight and EV-free period after kidney transplant. At the time of transplantation, six Letermovir patients (85.7%) in the PTLD group and 14 patients (35.9%) in the EV only group were seronegative for EBV (= 0.009). Data of donor EBV status before transplantation were available only in Letermovir a few cases, with no statistically significant difference observed between the groups. Table 2 Characteristics of patients value= 0.039). Maintenance immunosuppression regimen or history of rejection was not significantly different between the two groups. Six Letermovir patients were treated with pre-emptive RTX, none of whom developed PTLD, while the quantity of RTX-treated patients was too small to be statistically significant. The Cox proportional-hazard model was used to identify factors associated with an increased risk of developing PTLD after EV (Table 3). Values of 8.9 ng/mL for tacrolimus level and 35,900 copies/L for peak EBV titer were decided as cutoff values based on the receiver operating characteristic curve analysis. The areas under curve of tacrolimus and peak EBV titer were 0.745 (95% confidence interval [CI].