The patterns of organ damage in advanced systemic mastocytosis (SM) are associated with the type of disease, prior treatment, and mutation profile, according to a new study published in the journal Clinical Lymphoma Myeloma and Leukemia.

These findings can help clinicians decide which patients with advanced SM to enroll in clinical trials, the authors said. There are different subtypes of advanced SM, and the pattern of organ damage for each subtype is not well defined.

To describe the pattern of organ damage at initial presentation and at the time of enrollment in a clinical trial, and to evaluate clinicopathologic and molecular correlates of organ damage in advanced SM, a team of researchers led by Jason Gotlib, MD, MS, from the Stanford University School of Medicine analyzed 240 patients with the disease. Of these, 37 (15%) had aggressive SM, 165 (69%) had SM with an associated hematologic neoplasm, and 38 (16%) had mast cell leukemia. 

Patients with mast cell leukemia were more likely to need transfusions. They also had the largest liver and spleen volumes based on imaging data.

Read more about the subtypes of SM

When the researchers compared patients with SM with an associated hematologic neoplasm to patients with the other 2 types of SM, they found that the patients with an associated hematologic neoplasm had higher absolute neutrophil and monocyte counts. They also had mutations in the SRSF2, ASXL1, or RUNX1 gene. 

Patients with advanced SM or mast cell leukemia, on the other hand, had higher levels of tryptase and bone marrow mast cell burden. 

Finally, patients who had been treated with midostaurin had a larger bone marrow mast cell burden compared to those who had never received the drug. However, these patients less often met World Health Organization (WHO) criteria for liver damage and malabsorption. 

The researchers also reported that patients with at least 1 mutation in the SRSF2, ASXL1, or RUNX1 gene had lower median hemoglobin and platelet counts and higher direct bilirubin, alkaline phosphatase, and spleen volumes compared to those with the KIT D816V variant. They also showed more WHO-defined cytopenias and were more likely to meet the WHO criteria for hypersplenism.

Reference

Liang E, Perkins C, Lu R, et al. MPN-352 clinicopathologic and molecular correlates of organ damage across the spectrum of advanced systemic mastocytosis. Clin Lymphoma Myeloma Leuk. 2022;22 Suppl 2:S334. doi:10.1016/S2152-2650(22)01453-7