Post-transplant lymphoproliferative disorders in adult transplant recipients: Preliminary results of the multicenter italian FIL_PTLD study

Abstract

Abstract Background: Post-transplant lymphoproliferative disorders (PTLDs) are rare lymphomas that arise as complications of solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT), with a cumulative incidence of approximately 1% at 10 years. The Fondazione Italiana Linfomi (FIL) initiated the multicenter, observational, retrospective FIL_PTLD cohort study to assess PTLD management across Italian hematology centers. Primary objectives include the characterization of clinical features and survival outcomes, as well as the identification of prognostic factors affecting disease progression and mortality. Methods: Adult patients diagnosed with PTLD between January 2011 and December 2021 were retrospectively included. As of this preliminary analysis, 217 patients have been enrolled across 15 centers. Overall survival (OS) was measured from PTLD diagnosis, estimated using Kaplan-Meier method, and compared across groups with Cox model. Results: The median time from transplantation (SOT or HSCT) to PTLD diagnosis was 7.7 years, with shorter latency (p<0.001) observed in EBV-positive cases (2.0 years, range 0.58-11.58) compared to EBV-negative cases (8.25 years, range 5.08-14.75). Early-onset PTLD (within 2 years post-transplant) occurred in 24.0% of patients, while 76.0% had late-onset disease. Most cases followed SOT (92.1%), including kidney (37.5%), liver (36.0%), heart (19.0%), and lung (5.0%) transplants. Only 7.8% occurred after HSCT and 2.5% after combined transplants. The predominant histological subtype was monomorphic PTLD (90.8%), with diffuse large B-cell lymphoma in 68.2%, Burkitt lymphoma in 8.3%, lymphoplasmacytic lymphoma in 2.3%, marginal zone lymphoma in 4.6%, and classical Hodgkin lymphoma in 2.8%. Serum LDH was elevated in 58.6% of cases. Ann Arbor stage at diagnosis was advanced (stage III–IV) in 63.9% of patients. EBV-encoded RNA (EBER) status was available for 147 patients: 44.2% were EBV-positive, with 41.5% diagnosed early and 58.5% late post-transplant. Extranodal involvement was observed in 58.1% of cases, including central nervous system disease in 6.3%. Treatment consisted of immunosuppression reduction alone (11.4%), rituximab monotherapy (44.0%), chemoimmunotherapy (32.0%), chemotherapy alone (6.3%), other approaches (2.2%; surgery or steroids), or no treatment (3.4%). Overall response rates included complete response in 52.1%, partial response in 17.9%, stable disease in 11.4%, and progressive disease in 18.6%. With a median follow-up of 86 months (interquartile range: 52–128), 5-year and 10-year overall survival (OS) rates were 58% (95% CI, 50–66) and 51% (95% CI, 42–59), respectively. Multivariable analysis with Cox model identified age (HR per 1-y 1.02; p = .018), advanced stage (HR 2.61; p = .004), and ECOG performance status ≥2 (HR 2.23; p = .005) as independent predictors of inferior OS. EBER positivity (HR 1.65; p = .105), elevated LDH (HR 1.50; p = .157), and extranodal localization (HR 1.46; p = .277) were not significantly associated with survival. Conclusion: PTLD in adults predominantly arises after SOT and frequently presents in the late-onset form. Treatment approaches were heterogeneous across centers. Advanced age, poor performance status, and advanced stage at diagnosis were associated with worse overall survival.