PRIMARY CENTRAL NERVOUS SYSTEM POST‐TRANSPLANT LYMPHOPROLIFERATIVE DISORDER (CNS‐PTLD): A 20 YEARS RETROSPECTIVE SINGLE CENTER EXPERIENCE

Abstract

Introduction: Post-transplant lymphoproliferative disorder (PTLD) represent immunosuppression-related lymphoid or plasmacytic proliferation that occur in the setting of solid organ or hematopoietic cell transplantation. Primary central nervous system involvement of PTLD (CNS-PTLD) is a rare manifestation, present in 10-15% of all cases. Prior studies demonstrated that CNS-PTLD was associated with renal transplantation, EBV virus reactivation, large B cell lymphoma morphology and the use of mycophenolate mofetil. We present a single center retrospective analysis of CNS-PTLD patient outcomes over a 20-year period. Methods: We performed a retrospective chart review of patients with CNS-PTLD (defined as primary CNS lymphoma involvement at diagnosis) at the Princess Margaret Cancer Centre from 2000-2020. Patient and disease characteristics, responses, and survival outcomes were collected from the Lymphoma database and electronic patient records with REB approval. Results: Out of 183 PTLD patients we identified a total of 14 patients (7.6%) with CNS-PTLD were identified, all after solid organ transplant, 57% were female, median age at diagnosis 47 years [21-73], 64% had a renal transplant. Median time from transplant to PTLD was 113 months [4.3-337.3]. Thirty-six percent presented with an ECOG ≥ 2, 50% had an IPI score ≥ 3 and 86% had received mycophenolate mofetil as immunosuppression. Most patients were EBV positive (92%), monomorphic (92%), diffuse Large B Cell Lymphoma (71%), non-germinal center subtype (80%), with a median proliferation index of 70% [50-80]. Treatment of CNS-PTLD was heterogenous. All had immunosuppression reduction, 21% of the patients received radiation alone, 58% chemo-radiation (72% of them with rituximab), 21% chemotherapy alone (33% of them with rituximab), 35% of all treated patients had methotrexate containing regimens. Twenty-nine percent received further lines of therapy (n=4) and 1 patient underwent autologous transplantation. ORR to first line therapy was 50% (CR 21%, PR 29%), 1 patient had stable disease and 29% (n=6) had progressive disease (n=4) or died before response assessment (n=2). Of the four patients receiving salvage therapy, one achieved a CR, two a PR and one was not evaluable for response. 7 deaths occurred, the majority within 3 months of diagnosis (n=5), most from disease progression (n=4), all presenting an ECOG ≥2 at diagnosis. Median overall survival was 75.7 months. Conclusions: Our cohort demonstrated that CNS involvement occurs late after transplantation, frequently associated with EBV + monomorphic DLBCL subtype. In line with literature, mycophenolate mofetil use was observed in the majority of cases. Despite the aggressive nature of CNS-PTLD, half of our cohort patients were able to tolerate their initial treatment, achieved sustained response and a prolonged survival.