Post-transplant Lymphoproliferative Disorders (PTLD) in Kidney Transplant

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Background: PTLD are serious complications in solid organ (SO) and allogeneic hematopoietic stem cell transplants (T), ranging from benign proliferations to malignant lymphomas. PTLD accounts for 21% of cancers in SOT. Risk factors include Epstein-Barr virus (EBV) serostatus, recipient age, organ type, immunosuppression (IS), and genetic predispositions. Most PTLD originate from EBV-infected B cells proliferation due to IS but some 30-40% are not EBV-related. IS reduction (ISR) for immune function restoring, and chemotherapy (CT) is the treatment. We report our single center experience about incidence, risk factors, and treatment outcomes of PTLD in kidney transplant (KT) patients (pts). Methods: Between January 1, 1969, and August 31, 2023, 3024 adult pts underwent KT. Pts with a confirmed PTLD diagnosis (biopsy/clinical suspicion) were included in the study and PTLD cases classified according to the WHO criteria. KT pts without PTLD transplanted in the same period served as control. All the relevant clinical data before and after PTLD diagnosis were collected. End of follow-up was the last outpatient visit, death, or dialysis. After ISR, chemotherapy was coordinated with hematologists. Results: Monomorphic PTLD was diagnosed in 26 pts (0.8%):18 B-cell non-Hodgkin Lymphoma (nHL) (68%), 3 T-cell nHL, and 4 multiple myelomas. No early/polymorphic PTLD were detected. PTLD was diagnosed with a median (m) of 121 months (mos) after Tx (IQR 88-165). M-observation time was 187 mos (IQR 93-326). PTLD was EBV-related in 52% of cases. At diagnosis m-plasma creatinine was1.6 mg/dl (IQR 1.2-1.9) and m-proteinuria 0.3 g/24 hours (IQR 0.1-0.5). ISR was done in all but the 3 pts with a smoldering myeloma. In 24% of cases calcineurin inhibitor (CNI) was withdrawn, halved in 16%, discontinued in 8%. mTOR replaced CNI in 24% of pts. Steroid therapy was given at doses prescribed for CT. Pts survival was 44%. Twenty pts (75%) died for PTLD or its complications. Pts m-survival time was 12 mos (IQR 3-145), 77% of pts died with a m-creatinine of 1.9 mg/dl. Conclusion: In our series PTLD frequency of 0.8% and a mortality of 50% at one year are lower than literature rates. One and 5-year survival rate are 52% and 32% for monomorphic PTLD. Molecular-targeted drugs and immunomodulators may enable international multicenter studies to improve PTLD unfavorable prognosis.

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