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MANAGEMENT of toxic MTX concentrations

LEUCOVORIN rescue


For more than 30 years,
leucovorin rescue has been a cornerstone
of HDMTX treatment.1


  • Limited effectiveness in the presence of high-circulating MTX concentrations (>10 mmol/L for 48 hours or longer)2
  • Excessive doses may impact the MTX efficacy at the next HDMTX course2
  • Leucovorin rescue is essential, but it does not clear MTX from the body

DIALYSIS-based methods


Haemofiltration, high-flux haemodialysis, charcoal
haemoperfusion or haemofiltration, peritoneal
dialysis, exchange transfusion, plasma exchange.2


  • Limited Effectiveness 3
  • Success rates highly variable3
  • Repeated cycles may be required due to rebound effect1,4
  • Methods not readily available outside of major medical centres3
  • Risks associated with the insertion of vascularaccess devices, transfusion of blood products, electrolyte imbalances3

Abbreviations: HDMTX, high dose methotrexate; MTX, methotrexate.


Patients who have one or more of the following risk factors may experience delayed MTX clearance1,2,5:

  • Nephrotoxic comedication (NSAIDs,PPIs,etc)
  • BMI >=25 kg/m2
  • Renal insufficiency priot to HDMTX (i.e. CrCl < 60 mL/min)
  • Prior toxicity with HDMTX
  • Adult and elderly patients, as many as 60% of whom may have some degree of renal disfunction
  • Third spacing (pleural effusions, ascites, intracranial fluid)
  • Volume depletion due to vomiting, diarrhea, or other factors
  • Polyuria
  • Urine pH<7

BMI, body mass index; CrCl, creatinine clearance; NSAID, nonsteroidal anti-inflammatory drug; PPI, proton pump inhibitor.