Researchers presented the case study of a patient with advanced systemic mastocytosis who was diagnosed with high-risk acute myeloid leukemia in Clinical Case Reports. 

A 69-year-old man presented with neutrophilic leukocytosis (leukocyte count, 16.380 cells/μL) and maculopapular cutaneous lesions. A skin biopsy confirmed cutaneous mastocytosis.

Bone marrow histology demonstrated the presence of aggregates with more than 15 atypical mast cells with CD117+, CD34-, CD25+, and tryptase+; these were focally collagen (grade 2-3) and consensual to reticulin fibrosis. Peripheral blood demonstrated a cKITD816V mutation. His baseline serum tryptase levels were highly elevated at 184 μg/dL. The patient was also found to have osteopenia and diffuse osteosclerosis with micro-osteolysis at the skull as seen on computed tomography (CT) scans. 

“The further presence of more than 90% neutrophils in peripheral blood together with predominant maturing granulopoiesis in the bone marrow histological sample was suggestive of a concomitant chronic neutrophilic leukemia (CNL),” the authors of the report wrote. 

Read more about systemic mastocytosis etiology 

The patient was diagnosed as having indolent systemic mastocytosis with myeloproliferative neoplasm/myelodysplastic syndromes overlap. He was initiated on H1/H2 antagonists, vitamin D supplementation, and hydroxyurea, which allowed him to maintain moderate leukocytosis and a decrease in serum tryptase levels (73 μg/dL) for 4 years. 

A follow-up histological bone marrow analysis 3 years later demonstrated increased mast cell infiltration (30%-35%) with a neoplastic immunophenotype. In addition, he had less than 5% of CD34+ blasts. An abdomen ultrasound showed liver steatosis and mild splenomegaly. His physicians revised his diagnosis to smoldering systemic mastocytosis. 

One year later, he presented with weakness, a weight loss of 3 kg in 2 months, and malaise. Peripheral blood flow cytometry confirmed the evolution of the disease to acute myeloid leukemia as evidenced by 23% blasts with a CD33+, HLA-DR+, CD34+, and CD117+ immunophenotype. Hepatosplenomegaly was more pronounced and his serum tryptase shot up to more than 200 μg/dL. He was treated with a decitabine-venetoclax combination as first-line therapy. Midostaurin was prescribed as first-line therapy for his aggressive systemic mastocytosis. 

The patient underwent 4 cycles of chemotherapy, which decreased his serum tryptase levels. However, he developed grade 4 neutropenia and died from septic shock secondary to aplasia. 

“Even a strong combination of decitabine-venetoclax-midostaurin has a transient effect on acute myeloid leukemia and a mitigated effect on systemic mastocytosis,” the authors wrote. “Larger series are required to identify the best therapeutic strategy.”


Fazio M, Vetro C, Markovic U, et al. A case of high-risk AML in a patient with advanced systemic mastocytosisClin Case Rep. Published online July 17, 2023. doi:10.1002/ccr3.7134