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P15 Eculizumab treatment for a paediatric stem cell transplant (sct) patient diagnosed with transplant-associated thrombotic microangiopathy (tma)
  1. Lumb Poonam
  1. Imperial College Healthcare NHS Trust


Background TMA is a life threatening complication with a high mortality rate in SCT patients.1 The pathophysiology involves damage of the endothelial lining via over activation of the complement system which forms part of the innate immune system.2 Complications include; kidney damage, pulmonary hypertension and possible multi organ failure.1 Eculizumab is an agent that exhibits activity by inhibiting the complement system however dosing and effects in the paediatric population are lacking.1,2 An 18 year old patient was admitted to the paediatric SCT unit for a sibling haploidentical SCT. On day +48 she developed worsening acute kidney injury, hypertension and confusion. She was diagnosed with TMA confirmed via fragments on the blood film, blood in the urinalysis and an elevated lactate dehydrogenase (LDH).

Summary of the problem encountered The use of eculizumab is limited in paediatric centres. Furthermore there is limited dosing and monitoring information available for paediatric patients for the unlicensed indication of TMA. The urgent nature of the request of this medication due to the rapid deterioration of the patient meant there was no time to submit a non- formulary drug application or develop local protocol guidance. However when presented with a drug request for an unfamiliar drug several # had to be taken to ensure the safe and effective use of this drug.

Pharmacy contributions The first step involved determining an appropriate dosing regimen. A literature search was conducted alongside the attending consultant to determine this. Consequently the pharmaceutical company was contacted requesting a supply of the drug and required paperwork completed including a certificate of vaccination form. The next step involved calculating the total anticipated treatment cost as eculizumab is an extremely expensive drug. As this was non formulary and off label, the attending consultant took clinical responsibility and approval was sought from the Chief of Service and Chief Pharmacist. A prescription and administration proforma was designed which also included monitoring information and pre-medication required. Monitoring parameters to determine clinical efficacy were closely observed, this mainly included LDH and CH50 levels.

Outcome The patient clinically improved and eculizumab was stopped on day +222, the treatment course was longer than originally anticipated however CH50 levels were suppressed to <25%.

Lessons learned Although unlicensed eculizumab was effective against TMA complications experienced post SCT. This is however a high cost drug with complex monitoring requirements, also requiring a vast amount of support from pharmacy services.

Procedures are underway to develop local guidance for its use and also individual funding requests to be completed before treatment in order to gain funding for individual cases for this off label condition.


  1. Jodele S, Fakuda T, Vinks A, et al. Eculizumab therapy in children with severe hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Biol Blood Marrow Transplant2014;20:518–525.

  2. Jodele S, Fakuda T, Mizuno K, et al. Variable eculizumab clearance requires pharmacodynamic monitoring to optimise therapy for thrombotic microangiopathy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant2016;22:307–315.

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