Clinical Outcomes of Post-Transplant Lymphoproliferative Disease (PTLD): Role of Radiation Therapy in Improvement of Disease Response

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Post-transplant lymphoproliferative disease (PTLD) is a rare disease complicating solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT). Management of PTLD includes immunosuppression reduction, systemic therapy, surgery and radiation therapy (RT). Data regarding the efficacy and outcomes of radiation therapy in treatment of PTLD is limited. Here, we report our institution's experience with the treatment of PTLD including RT outcomes.We retrospectively reviewed patients with biopsy proven PTLD who were treated at our institution. After obtaining Institutional Review Board approval, patient demographics, disease characteristics, treatment modalities and follow-up data were recorded. Disease response before and after RT use was assessed per response evaluation criteria in solid tumors (RECIST) 1.1 including complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan Meier method. Cox Proportional Hazards models were utilized to determine variables associated with OS.We identified and reviewed medical records of 48 patients with PTLD. Median follow up was 38 months. The median age was 58 (range:10-81). The majority were white (79%) and male (56%). 50% of the cohort were SOT recipients, 44% were HCT recipients and 6% underwent combined transplants. The most common site of PTLD was CNS (29%). Monomorphic PTLD was the most common histological type with EBV positivity in 75% of patients. Median time from SOT-to-PTLD was 77 months (range:5-322) and HCT-to-PTLD was 5 months (range: 2-46). Systemic therapy was the most commonly used modality in 92% of patients. The most commonly used regimen was Rituximab monotherapy. Surgery was employed in 10% of patients. RT was utilized after induction therapy in 37.5%. The most common treated site was the brain (61%). Overall response of the entire cohort was 87% (58% CR and 29% PR), 6% achieved SD and 7% had PD. Among the RT cohort, 55% achieved CR, 33% achieved PR and 12% had SD. Local control rate was 100%. Of 21 patients who did not respond completely to induction therapy, 6 patients with initial PR achieved CR, 1 patient with initial SD achieved CR, 1 patient with initial PD achieved CR, and 2 patients with initial PD achieved PR and SD, respectively, after RT receipt. The median RT dose was 3,600 cGy (range: 2400-4600). 3- and 5-year PFS were 90% and 85%, respectively, while 3- and 5-year OS were 70% and 55%, respectively. Cox hazards modeling confirmed that HCT receipt was associated with better OS on multivariate analysis (HR 0.26, 95% CI 0.008- 0.671, P = 0.007).RT provides excellent local control and improves overall disease response of PTLD. Further optimization and standardization of combined modality paradigms are needed to improve clinical outcomes of this rare entity.