INFANTILE AGGRESSIVE SYSTEMIC MASTOCYTOSIS TREATED WITH ORAL MIDOSTAURIN

Abstract

<h3>Introduction</h3> Systemic mastocytosis accounts for less than 10% of all pediatric mastocytosis cases. Midostaurin, a cytoreductive multi-kinase inhibitor, is approved for use in adult systemic mastocytosis. There are no FDA-approved cytoreductive therapies for pediatric patients. <h3>Case Description</h3> A 3-month-old male presented with diffuse pruritic patches and hepatosplenomegaly, in the setting of a markedly elevated tryptase of 187 ng/mL (<11.4mg/mL). Bone marrow biopsy showed multifocal mast cell infiltrates with a subset being spindle shaped. Mast cells immunostaining was positive for tryptase, CD117, CD2 and CD30. Skin biopsy revealed superficial dermal mast cell infiltration. Serum KITD816V mutation was positive. There were no cytopenias. The patient was started on a regimen of H1 and H2 antihistamines and oral cromolyn. Three months later, he presented with fever and progressive hepatosplenomegaly. Labs were notable for: increased tryptase (234 ng/mL), anemia (hemoglobin 9.3 g/dL), mild thrombocytopenia (133 k/uL)<i>,</i> elevated prothromobin time (15.9 sec [11.7-14.7 sec]) and low albumin (2.7 g/dL [2.9-5.5g/dL]). Local IRB approval and FDA emergency expanded use was obtained for oral midostaurin 30mg/m² every 12 hours with weekly monitoring of CBC and tryptase. Within 3 weeks of starting, the tryptase declined to 129 ng/mL and the patient had near complete resolution of head and neck lesions with reduction in hepatosplenomegaly. <h3>Discussion</h3> To our knowledge this is the second case of infantile systemic mastocytosis where oral midostaurin rapidly decreased serum tryptase and improved clinical symptoms without notable adverse effects. This treatment will be continued until normalization of serum tryptase unless adverse effects develop.