Abstract: FR-PO1285
Safe Delivery of High-Dose Methotrexate to a Patient with Primary Central Nervous System Post-Transplant Lymphoproliferative Disorder and ESRD on RRT
Session Information
- Onconephrology: Diagnostic Dilemmas, Therapy-Related Toxicities, and Clinical Cases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1600 Onconephrology
Authors
- Villanueva, Denise Nicole De Leon, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, New York, United States
- Augustine, Elaine, NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, New York, United States
- Galvelis, Tyler R., NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, New York, United States
- Orjuela, Manuela A., Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States
- Lattanza, Brittany, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States
Introduction
High-dose methotrexate (HD-MTX) is a key chemotherapeutic agent in the treatment of primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD). Because it is predominantly renally cleared and is also nephrotoxic, its use in patients with significant renal impairment is associated with an increased risk of delayed clearance and severe systemic toxicity. Given these, there is limited data on its use in patients with end-stage renal disease on renal replacement therapy (ESRD on RRT), highlighting an important clinical challenge.
Case Description
We present a 19-year-old female with heart transplant complicated by disseminated Strongyloidiasis and multiorgan failure, including ESRD on RRT, who presented with headaches, hypersomnolence and visual disturbances and was diagnosed with EBV-positive diffuse large B-cell PCNS-PTLD of the left caudate nucleus. A novel protocol to safely administer HD-MTX was developed by a multidisciplinary team including pediatric nephrology, oncology, clinical pharmacy, critical care and transplant cardiology.
Because HD-MTX elimination is prolonged and pharmacokinetically variable in ESRD, the patient was transitioned from intermittent hemodialysis to continuous renal replacement therapy (CRRT) right before infusion and continued until MTX clearance was acceptable (defined as a level <0.1 umol/L). HD-MTX was dose-reduced by 50% and CRRT clearance was prescribed at 2000-3500 ml/1.73m2/hr (estimated GFR 33-58 ml/min/1.73 m2). Continuous venovenous hemodiafiltration modality was used to maximize HD-MTX clearance given that approximately 50% of the drug is protein bound. Real-time MTX pharmacokinetic monitoring and timed leucovorin rescue were done.
The patient successfully tolerated five cycles of HD-MTX on CRRT, with radiographic and clinical improvement and no dose-limiting toxicities.
Discussion
To our knowledge, this report highlights the first successful HD-MTX administration to an adolescent patient with pre-existing ESRD using CRRT. This case demonstrates how CRRT can play a critical role in optimizing the delivery and expanding the use of nephrotoxic medications including some chemotherapeutic agents in patients with ESRD. Further studies are warranted to develop standardized guidelines on how CRRT can be utilized for this vulnerable cohort.