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Original Research Open Access

Reduced Intensity Therapy for Primary Central Nervous System Post-Transplant Lymphoproliferative Disorders is Associated with Preserved Survival Outcomes: A Twenty-Year Single-Institutional Experience 

  • 1Department of Medicine, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA
  • 2Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA
  • 3Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA
  • 4Department of Pharmacy, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA
  • 5Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine & Public Health, Madison, WI; UW Health Transplant Center, USA
  • 6Department of Human Oncology, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA
  • 7Division of Hematology, Medical Oncology and Palliative Care, UW, Madison, WI, USA
+ Affiliations - Affiliations

Corresponding Author

Julie E. Chang, jholderchang@gmail.com

Received Date: June 11, 2025

Accepted Date: July 28, 2025

Abstract

Primary central nervous system post-transplant lymphoproliferative disorders (PCNS-PTLD) are rare complications of transplantation. Due to PCNS-PTLD’s scarcity, optimal treatments, risk factors, and outcomes are poorly characterized. By retrospective analysis of 20 patients treated at the University of Wisconsin between the years 2000–2022, we aimed to describe patient/disease characteristics, therapies received, and survival outcomes of PCNS-PTLD. Three separate clinical and pathological databases were reviewed to identify cases, with all patients having at least 2 years of long-term follow-up. Kaplan Meier survival curves were generated for cohorts treated from 2000–2010 (Cohort 1) and 2011–2022 (Cohort 2), with univariate and multivariable analysis performed for baseline variables associated with progression-free (PFS) and overall survival (OS). The median PFS was 59.2 months (95% confidence interval [CI], 36.0–78.9 months) and the median OS was 71.2 months (95% CI, 47.6–91.6 months). Univariate analysis of patient sex, age, time to PTLD diagnosis, transplant type, transplant indication, time to treatment, therapy type, and baseline lactate dehydrogenase (LDH) showed that only lower LDH was associated with improved PFS (p=0.008) and OS (p=0.008). Over 2 decades, treatment practices had dramatically shifted from the frequent use of high-dose/intrathecal methotrexate and whole brain radiation in 75% of patients in Cohort 1, to use of first-line rituximab in 83% of patients in Cohort 2. Despite these key changes, there was no significant difference in OS or PFS between decades. Our findings support the use of less toxic therapies such as rituximab for PCNS-PTLD and encourage further investigation to optimize therapeutic approaches. 

Keywords

Post-transplant lymphoproliferative disorder, Immune suppression, Solid organ transplant, Lymphoma, Rituximab, Methotrexate, Brain radiotherapy

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