Post-Transplant Lymphoproliferative Disorders (PTLD) in a Referral Center

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Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare and potentially life-threatening complication of solid organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (HSCT), affecting up to 10-20% of recipients. Prognosis is highly variable, and several prognostic factors have been identified. Real-life experience is needed to better understand this rare entity. Methods: We retrospectively collected data on all PTLD cases following SOT and HSCT diagnosed at Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy, between 2007 and 2023. All patients were ≥18 years old at the time of diagnosis, with diagnosis of destructive PTLD occurrence from 2007 to 2023, and received active treatment for PTLD. Results: A total of 46 PTLDpatients (pts) were included: 8 (17%) after lung, 19 (41%) after liver, 16 (35%) after kidney transplant (Tx), and 3 (7%) after HSCT. Within a cohort of 2171 transplanted pts, the incidence of PTLD was 0.17 per 100 patient-years for kidney, 0.18 for lung, 0.22 for liver, and 0.07 for bone marrow tx. The median age at PTLD diagnosis was 47 years (range 18-79), with 35 (76%) having advanced-stage disease, 13 out of 43 (30%) with an ECOG score ≥ 2, and 15 out of 43 (35%) presenting with B symptoms. Increased LDH levels were observed in 26 out of 37 (70%) cases. PTLD-IPI scores of 2-3 were found in 17 out of 37 (46%) cases. Histologically, DLBCL was the most common subtype (78%) and 3 (7%) polymorphic PTLD. The median time from Tx to PTLD diagnosis was 64 months (mos) (range 2-378) in the overall population, varying from 3 (range 2-56) for lungs to 111 mos (range 2-241) for kidneys. Twelve (26%) cases occurred within the first year (early-onset) after Tx. EBV positivity was detected in 17 out of 39 (43%) pts with available information, with the highest rates in lung Tx (75%) and HSCT (100%). At diagnosis, pts were receiving a median of 2 immunosuppressants (IS) (range 0-3): 21 (47%) were receiving prednisone, 45 (98%) a calcineurin inhibitor, and 21 (47%) mofetil mycophenolate. IS were reduced in all pts, with 2 pts requiring no further therapy. Nine (20%) pts received single-agent rituximab, all of whom experienced progressive disease. Two pts were treated with RIS and concomitant excisional surgery. Chemo/chemo-immunotherapy was administered to 42 (91%) pts (upfront in 37 pts due to disease burden). The overall response rate was 70%, with a complete response (CR) in 55%. No graft rejection was reported. With a median follow-up of 20 mos (1-161), 22 (48%) pts relapsed or progressed, with a median progression-free survival of 25 mos (1-161). At the time of analysis, 22 (48%) pts had died (82% from lymphoma): 4 lung, 10 liver, 9 kidney and no HSCT Tx pts were alive. The median overall survival (OS) was 66 mos (1-161). Higher mortality rates were associated with PTLDs after HSCT (HR 10, 95% CI 2.7-42.5) and after lung Tx (HR 15, 95% CI 0.5-4.5), with a median OS of 2 mos (1-8) and 22 months (1-104), respectively. Increased LDH (HR 7.3, 95% CI 1.7-31.8), ECOG ≥ 2 (HR 4.5, 95% CI 1.9-10.8), B symptoms (HR 3.5, 95% CI 1.4-8.3), early-onset PTLD (HR 3.1, 95% CI 1.2-7.5), and single-agent rituximab treatment (HR 2.6, 95% CI 0.9-6.8) were significantly associated with worse survival. PTLD-IPI was a strong predictor of OS (HR 2.5, 95% CI 1.4-4.5). At multivariate analysis, only increased LDH, EBV positivity, and age >60 years maintained a prognostic role. Conclusions: We found that HSCT and lung Tx were more frequently EBV positive, of early-onset and associated with worse prognosis. Beside age and LDH, EBV positivity emerged as significant prognostic factor.

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