HIGH-DOSE INTRAVENOUS METHOTREXATE WITH HIGH-FLUX HAEMODIALYSIS IN TREATMENT OF POST-TRANSPLANT, CENTRAL NERVOUS SYSTEM LYMPHOMA WITH END-STAGE KIDNEY DISEASE

E VAUGHAN1, J YEUNG2, C BROWN2,S CHADBAN1, N THIAGARAJAH2, J SAUNDERS1

1Renal Department Royal Prince Alfred Hospital, Sydney, NSW; 2Institute of Haematology, Royal Prince Alfred Hospital, Sydney, NSW

Background: High-dose intravenous methotrexate (HD-MTX) is an integral part in primary central nervous system (CNS) lymphoma treatment. Predominant renal excretion of methotrexate limits its use in patients with end-stage kidney disease (ESKD). We report a case of post-transplant CNS lymphoma treated with methotrexate and extended hours high-flux haemodialysis.

Case Report: A 41-year-old man with a cadaveric renal transplant of 26 years for reflux nephropathy, presented with headache and absence seizures despite previously well-controlled epilepsy. He had chronic allograft nephropathy on weaning triple therapy immunosuppression. Multi-focal lesions found on cerebral magnetic resonance imaging (MRI) were biopsied to confirm monomorphic post-transplant lymphoproliferative disorder (PTLD) without metastatic disease. Transition to haemodialysis was complicated by increased clearance of anti-epileptic drugs (AEDs) leading to partial seizures. Whole brain radiotherapy (WBRT) was undertaken for initial control, followed by three cycles of dose-escalated methotrexate. This was followed by eight-hour high cut-off haemodialysis, and leucovorin rescue with close monitoring of methotrexate levels and increased dose of AEDs. Follow-up MRI, and neurological PET-CT confirmed remission 6 weeks post-treatment.

Methotrexate is primarily cleared in the urine, which limits its use in ESKD due to nephrotoxicity and myelosuppression. In conjunction with high-flux haemodialysis, HD-MTX ranging from 1 to 9.5g/m2 has been scarcely described for solid organ and haematological malignancies. Confounding management issues included the associated clearance of AEDs with extended-hours haemodialysis. This was managed with intra-dialytic drug dosing and up-titration. Adequate clearance of methotrexate occurred despite increased dosing. Residual renal function may have contributed to prompt drug clearance.

Conclusions: For CNS lymphoma, HD-MTX with high-flux haemodialysis should be considered a viable option in candidates with ESKD without other contraindications.

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