A Single-Center Analysis of Pathologic and Clinical Features, Treatment, and Outcomes in Post-Transplant Lymphoproliferative Disorder (PTLD)

PTLD is a rare heterogenous group of lymphoproliferative diseases arising from chronic immunosuppression after solid organ or allogeneic stem cell transplantation (allo-SCT). Treatment of PTLD involves a sequential approach with immunosuppression reduction and chemoimmunotherapy.

This is a retrospective single-center observational analysis of adult patients from 2011-2024 with biopsy-proven PTLD. We describe demographics, pathologic, clinical characteristics, immunosuppressive regimen, treatment, response and rejection rates. Kaplan Meier method was used to assess progression free survival (PFS), overall survival (OS), and disease specific survival (DSS).

We included 60 patients with median age of 62 (range 31-83); 65% were male. Patients underwent transplantation of kidney (32%), liver (32%), heart (14%), lung (10%), pancreas (2%), allo-SCT (10%), and 17% underwent multiple transplantations. Histologic subtypes included hyperplasia (2%), polymorphic (5%), and monomorphic (93%). Monomorphic subtypes most commonly included DLBCL (66%), HGBCL (7%), CHL (7%), MZL (5%). At diagnosis 45% were EBV+ on IHC. Out of 45 (70%) patients with extranodal disease, GI tract, liver, and CNS were involved in 47%, 29%, and 13% respectively. At diagnosis, 80% were on multiple immunosuppressive medications, which included prednisone (48%), cyclosporine (17%), tacrolimus (80%), mycophenolate (47%), azathioprine (18%), sirolimus (3%), everolimus (2%), belatacept (3%). For frontline treatment, 3% were treated with immunosuppression reduction alone, 15% with rituximab, 72% with chemoimmunotherapy, 2% with radiation, and 7% untreated or passed before treatment initiated. Of those receiving chemoimmunotherapy upfront, majority received R-CHOP (53%), R-EPOCH (19%), R-CVP (5%), and 2% each of Pola-RCHP, R-CEOP, and BV-AVD. Median follow-up was 39 months. ORR was 91%. CRR was 80%. Relapse rate was 12%. The 4-year PFS, OS, and DSS were 40% (95% CI, 25-54), 43% (95% CI, 27-57), and 71% (95% CI, 52-84%) respectively. In solid organ transplant patients, 15% experienced graft rejection after PTLD diagnosis. Out of these, 38% were lung, 25% kidney, 25% liver, and 13% pancreas.

Here we present a large real-world analysis of PTLD patients at a single-center. Our cohort had higher rates of frontline treatment with chemoimmunotherapy compared to prior studies (where ~40% were treated upfront with rituximab and ~55% with chemoimmunotherapy). This cohort achieved high ORR and CRR and comparable PFS and OS. However further investigation is needed to explore high-risk features and the molecular landscape of PTLD to risk-stratify and optimize the treatment approach in these patients.