PC2183: Systemic Mastocytosis in an Adolescent Undergoing Treatment for Acute Myeloid Leukemia

Introduction: Pediatric hematologic malignancies are defined by the abnormal clonal proliferation of a distinct cell. In the case of acute myeloid leukemia (AML), this clonally derived cell is of myeloid origin. What has been rarely described is a concurrent clonal population of mast cells. This represents a unique challenge as mast cells do not respond to traditional chemotherapeutics used to treat AML and the significance of this population is not well described in the literature. We describe an adolescent male with acute myeloid leukemia (AML) who was found to have a concurrent mast cell population at diagnosis that progressed through the course of AML treatment.

Case Description: A previously healthy 17-year-old male presented with fever, headache, malaise and fatigue; he was tachycardic with pallor and an enlarged left supraclavicular lymph node. Initial laboratory evaluation revealed pancytopenia with blast cells evident on the peripheral smear. Diagnostic evaluation determined that he had AML with a t(8:21) translocation and D816V c-kit and NPM1 mutations with evidence of CNS disease. Additionally, his initial bone marrow biopsy demonstrated a concurrent mast cell population of 6.5% of uncertain significance. He was treated for his AML per the Children’s Oncology Group protocol AAML1831. His treatment course was complicated by multiple infections, including fungal lung disease and an episode of anaphylaxis after treatment with amphotericin B. His AML was found to be in remission after Induction I, and remains as such now two months post-therapy. Over the course of treatment, his bone marrow mast cell population progressed and further evaluation revealed that these cells possess both the t(8;21) translation and the D618V c-kit mutation, meeting the diagnostic criteria for systemic mastocytosis. Serum tryptase levels were followed during the course of his treatment, with peak of 205 mcg/L. Currently post–treatment, his tryptase level is hovering between 36.6 and 46.1 mcg/L and his mast cell population persists.

Discussion: This patient’s systemic mastocytosis remains of unclear etiology. The original leukemic myeloid clone and mast cell populations both possessed the same c-KIT mutation and t(8;21) translocation but from whence the mutation originated – the myeloid lineage, the mast cell lineage, or both – is uncertain. During the course of his AML treatment, treatment for his systemic mastocytosis was considered but was deferred as it can pose increased mortality risk in conjunction with AML treatment. Now that his AML is in remission his mast cell population is decreasing and his tryptase is improving. The best course of treatment for this is unclear, as is his risk for relapse and ultimate prognosis.

Conclusion: AML remains a difficult disease to treat in the adolescent population with overall survival of only 57%. Concurrent Systemic Mastocytosis presents an even larger treatment challenge with little guidance on best practice approaches.