POST TRANSPLANT LYMPHOPROLIFERATIVE DISORDERS: AN INTERNATIONAL REGISTRY STUDY (THE PLATO STUDY)

Post-transplant lymphoproliferative disorders (PTLD) comprise a spectrum of rare lymphoid disorders that are one of the most serious complications after solid organ transplant (SOT) or hematologic stem cell transplant (HSCT). The incidence has increased in recent years, and could be explained by increase of transplant rates, including also the haploidentical transplant. T cell immunosuppression and Epstein Barr virus (EBV) status have an important role in the its development. Treatment of PTLD varies considerably according to subtype, ranging from reduction in immunosuppression (RIS) to rituximab, with or without chemotherapy for high-risk or RIS-refractory cases, considering that Diffuse large B cell lymphoma (DLBCL) is the most frequent subtype. Due to its rarity, available data result from retrospective series related to major organ transplant centers. However, there is a lack of hematological community data which could be crucial to better definition of the clinical characteristics of PTLD patients, analysis of treatment outcomes, investigation of the optimal therapy approaches, and also further scientific questions for future studies. Our work aims to improve our knowledge about PTLD universally, describing the clinical-epidemiological profile and therapeutic strategies, as well as its clinical outcomes. PLATO study regards from a retrospective international registry focused on patients > 18 years old, diagnosed with PTLDs in rituximab era, specifically from 2004 to 2024.The primary endpoint was an analysis of patient’s characteristics and first-line regimes. The study was approved by the IRB of the Coordinating center on 31/07/2024. From November 2024 to July 2025, 134 PTLDs patients were registered at 12 sites in 9 different countries (Brazil, Croatia, Italy, Poland, Romania, Turkey, Argentina, Mexico, Uruguay). Median age at diagnosis was 49.6 yo (range 18 – 77yo), with 64% (86) of male. The median time from transplant (both SOT or HSCT) to PTLD diagnosis was around 45 months. Almost 92% (124/134) of PTLDs arises after SOT and only 8% (10 pts) after ASCT, mostly kidney (49.5%) and liver (35%) transplant, of note only 8 in combined transplant. The most common PTLD subtype was monomorphic (78%), with 87% of patients with CD20 positive, and the majority was DLBCL. Data on EBER positivity was available on 94 patients, with 68% of patients with EBER positive on immunohistochemistry. The majority had advanced stage, but without B symptoms and extranodal organ involvement in 72% of cases. Considering treatment decision, RIS was indicated in 69 % (93 pts), rituximab with or without chemotherapy was performed in 76% (102 pts). The ORR was 91% (all evaluable response), 78% achieved CR after 1st line, and 69% did not relapse. Among patients with known EBER status and response to treatment, ORR was not different between EBER positive and negative. In an exploratory multivariable model, age; transplant type and treatment regime, EBR was not an independently associated. The PLATO study is the first-ever global patient registry of PTLDs. The results of this first analysis regarding to epidemiologic profile was concordant with historically data. In our data, the EBER status was not independently risk, and maybe the viral status alone may be insufficient to predict early treatment benefit, but the proportion of missing EBER data was high and it could impacted in results. We expect to improve these results continue with the PLATO collaborate study.