#4585 post-transplantation lymphoproliferative disorder: comparison of risk and prognostic factors between kidney and other organ transplant recipients

Abstract Background and Aims Post-transplantation lymphoproliferative disorder (PTLD) is a potentially fatal complication of transplantation, pathogenesis of which remains to be fully understood. In solid organ transplant recipients, the risk of disease development is associated with graft type and is lowest for kidney (KTR), intermediate for liver (LTR) and high for lung (LngTR) transplant recipients. The aim of this study was to investigate the factors contributing to the development and treatment outcomes of PTLD and compare their impact on the populations of KTRs, LTRs and LngTRs. Method In this retrospective cohort study we have included all KTRs, LTRs and LngTRs diagnosed with PTLD at four transplantation centers in Poland between 2002 and 2022. The following data were collected from the patients’ medical records: immunosuppression (IS), viral infections, PTLD type, treatment and outcomes. Mann-Whitney U-test was used to assess the differences in group composition, and univariate Cox regression was used to determine the impact of variables upon PTLD time of onset and patient survival. p-values below 0.05 were considered statistically significant. Results We identified 31 KTRs, 31 LTRs and 5 LngTRs who fulfilled the inclusion criteria. Among the patients of the transplantation center leading this study, PTLD was diagnosed in 22 (0.82%) out of 2699 KTRs and 29 (2.03%) out of 1386 LTRs. Two thirds of the patients were male, the median age at first transplantation was 39 years and the median age at PTLD diagnosis was 48 years. KTRs and LTRs significantly differed in IS treatment: more KTRs used steroids (GCS, p = 0.042) and cyclosporin (CsA, p = 0.001), more LTRs used tacrolimus (TAC, p<0.001) and anti-CD25 induction (p = 0.003). KTRs developed PTLD later than LTRs (141 months after transplantation vs 53 months, p = 0.004) and LngTRs (5 months after transplantation, p = 0.001). Monomorphic PTLD was the most frequent in KTRs (80.6%, p = 0.032). Initial IS treatment reduction was used in 91% of all patients. The groups did not significantly differ in the type of PTLD treatment. TAC had the opposite effect on PTLD time of onset in KTRs (HR = 2.92, 95%CI 1.35-6.34, p = 0.007) and LTRs (HR = 0.18, 95%CI 0.04-0.89, p = 0.036). At the end of the observation period 16.7% of KTRs, 51.6% of LTRs and 80% of LngTRs were alive. Complete remission was achieved in 48.4% of KTRs, 61.3% of LTRs and 80% of LngTRs. KTRs had the highest rate of loss to follow up at 41.4%. Patient survival was longer in patients who were treated with anti-CD20 monotherapy (HR = 0.28, 95%CI 0.08-0.96, p = 0.042) and surgery (HR = 0.33, 95%CI 0.12-0.91, p = 0.031). Conclusion KTRs develop PTLD significantly later than LTRs and LngTRs, and disease onset is associated with TAC use. Low KTR survival rate is related to the high rate of loss to follow up (e.g. loss of graft function and return to hemodialysis). Surgical treatment, used mainly in focal PTLD improves patients’ survival. The positive effect of anti-CD20 monotherapy on patients’ survival reflects the efficacy of current stratified treatment regimens for PTLD.