Backgound Aggressive systemic mastocytosis is a very rare life-threatening diagnosis whereby mast cells accumulate in internal tissues and organs. There are limited case reports of this condition, particularly in children, and is associated with poor prognosis.

Situation We present a case report of a child who was diagnosed as a neonate with cutaneous mastocytosis and subsequently developed massive hepatosplenomegaly, cytopenia and failure to thrive. Genetic testing was carried out, confirming somatic changes in the KIT proto-oncogene receptor tyrosine kinase, which controls important cellular processes. Her twin was unaffected. Treatment goal was to reduce disease burden and if clinically fit enough, to proceed with allogenic stem cell transplantation.

Contribution of the Pharmacy Team This case presented numerous pharmaceutical challenges. Drug reactions can be severe and life-threatening resulting in anaphylaxis. Therefore, management of paediatric systemic mastocytosis includes strict avoidance of triggers of histamine; including: drugs, infection, allergens and physical stimuli. The pharmacy team advised on the most appropriate analgesia, infection prophylaxis, anti-mediator therapy and mast-cell targeted treatment options.

First line therapy for adult patients with this condition is midostaurin. This is formulated as a 25mg capsule, which is the only licensed preparation. Due to the rarity of this condition in paediatrics, only case reports were available. Suggested initial dosing of 30mg/m² twice daily would provide a dose of 7.8mg twice daily in a 4kg infant. The manufacturer was contacted to request supply of an alternative formulation if available on a compassionate access basis to meet the clinical need to this patient. Initially the manufacturer was unable to support this request in a timely manner which led us to pursue second line therapy with cladrabine.

Pharmacist advised on cladrabine dosing based on chemotherapy protocols, liaised with procurement to source drug and facilitated set up of drug using electronic prescribing system, supported consultant to prescribe and nursing staff to administer drug.

Without the contribution of the pharmacy team, it is likely that this patient would not have received treatment in a timely manner and drugs may have been inadvertently prescribed and administered that could trigger histamine release.

Outcome Patient received three cycles of cladribine using doses described in LCH-IV protocol. Hepato-splenomegaly was reduced and counts normalised. There was no visible improvement of skin lesions. The manufacturer of midostaurin responded several weeks later granting the supply of a trial stock liquid formulation on a compassionate basis.

Lessons Learnt Medicines governance around compassionate access schemes are lengthy and therefore second line treatment was required. Consideration of most appropriate analgesia and infection prophylaxis was researched and prescribed for patient.