Introduction: Posttransplant lymphoproliferative disorder (PTLD) is a rare but serious complication that can occur following solid organ transplant and hematopoietic stem cell transplant (HSCT). It is associated with prolonged immunosuppression and is often driven by Epstein-Barr virus reactivation. Over the past two decades, an increasing incidence of PTLD has been observed, coinciding with a rise in transplantations, older recipient age, and evolving immunosuppressive regimens. This study aims to describe the demographics, clinical characteristics, including transplant type, immunosuppressive regimen, and histologic subtype, and survival outcomes among adults diagnosed with PTLD.

Methods: Data were analyzed for patients ≥18 years old with a diagnosis of PTLD in the United States (US), as reported in the TriNetX database between 1993 and 2025. Sociodemographic and disease characteristics were studied. Overall survival (OS) was assessed using Kaplan-Meier analysis. OS comparisons were performed between subgroups, including sex, age, race and ethnicity, year of diagnosis, and transplanted organ.

Results: A total of 2674 patients were identified. Median age at diagnosis was 57 years, and 60.2% were male. Racial and ethnic distribution was predominantly non-Hispanic White (65.6%), followed by non-Hispanic Black (11.7%), Hispanic (8.7%), non-Hispanic Asian/Native Hawaiian/Other Pacific Islander (4.9%), non-Hispanic other/unknown race (9.2%). Most patients resided in the South (32.7%) or Northeast (32.6%) of the US, with fewer in the Midwest (18.7%) and West (15.7%).

Most commonly received transplants were kidney (30.1%), liver (15.9%), and HSCT (8.6%), followed by heart (7.7%), lung (5.2%), and pancreas (0.4%). Notably, 19.6% underwent multiple transplants. At diagnosis, the most common immunosuppressant was tacrolimus (45.0%). Other agents included prednisone (6.2%), cyclosporine (5.8%), sirolimus (5.8%), dexamethasone (4.8%), azathioprine (3.1%), methylprednisolone (1.9%), everolimus (0.7%), ibrutinib (0.6%), ruxolitinib (0.6%), mycophenolate (0.3%), basiliximab (0.2%), and thymoglobulin (0.1%).

Extranodal, bone marrow, and CNS involvement were present in 29.5%, 1.9%, and 1.8% of cases, respectively. Among cases with known histology, B-cell PTLD was most common (67.3%), followed by T-cell PTLD (5.7%), Hodgkin lymphoma (4.4%), and others (22.6%).

At last follow-up, 910 patients (34.0%) had died. Median time from diagnosis to end of follow-up was 1137.5 days; 1429.5 days for survivors and 615.5 days for those who died.

Survival time varied significantly across age quartiles at diagnosis, defined as 18-39, 40-56, 57-65, and ≥66 years. Kaplan-Meier analysis demonstrated a clear separation of survival curves, with median OS of 254, 185, 82, and 61 months from youngest to oldest quartile, respectively (p<0.0001).

Survival outcomes were also analyzed based on year of diagnosis quartiles: 1993-2015, 2016-2018, 2019-2020, and 2021-2025. Kaplan-Meier analysis showed significantly improved survival rates for patients diagnosed more recently (p<0.0001).

No statistically significant differences were noted in OS across sex, racial and ethnic groups, or US region of residence.

Survival outcomes varied notably by type of transplanted organ. Those who received lung transplants had the poorest median OS at 1583 days, while kidney and liver transplant recipients demonstrated comparatively better outcomes, with median OS of 5057 days and 3560 days, respectively. Median OS for heart transplant recipients was 2730 days, and for those who underwent HSCT, 2643 days.

Regarding treatment, only 10 patients received bispecific antibodies (glofitamab, epcoritamab, or mosunetuzumab) and only 23 patients received CAR-T therapy.

Conclusion: This study represents one of the largest real-world analyses of PTLD in adult patients in the US, utilizing the TriNetX dataset spanning over three decades. Improvement in OS in more recent years likely reflects advancements in monitoring and early intervention, as well as earlier diagnosis. Statistically significant differences in OS based on transplanted organ highlight important disparities and suggest a need for further investigation into organ-specific risk factors, surveillance strategies, and treatment approaches. These findings underscore the importance of continued efforts to optimize PTLD prevention, particularly for high-risk transplant populations.

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2025
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