Mutations in systemic mastocytosis (SM) may have more prognostic value than abnormal karyotype, according to a study published in the American Journal of Hematology.

SM is divided into 5 morphological categories by the World Health Organization: indolent SM (ISM), smoldering SM, SM with an associated hematological neoplasm (SM-AHN), aggressive SM (ASM), and mast cell leukemia (MCL). The prognostic value of mutations in SM, including ASXL1, RUNX1, and SRSF2, has been shown in previous studies, but the prognostic relevance and incidence of cytogenetic abnormalities have not been adequately studied.

In this retrospective study, researchers collected and analyzed cytogenetic data from 348 patients with SM (age range: 18-88 years; 53% male), of whom 129 patients were further screened for adverse mutations. Of the patients, 142 had ISM, 155 had SM-AHN, 49 had ASM, 2 had MCL, and none had smoldering SM. Mutations were detected in 30 patients. Abnormal karyotypes were found in 53 patients, with incidences of 6% and 22% for ISM and advanced SM (comprising SM-AHN, ASM, and MCL; P <.001), respectively.

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Statistical analysis showed signification correlations between abnormal karyotype and male sex (P =.002), age greater than 60 years (P =.04), thrombocytopenia (P <.001), and anemia (P <.001). No significant association was found between abnormal karyotype and presence of adverse mutations, but abnormal karyotype was correlated with inferior survival (hazard ratio [HR] 3.0).

The prognostic relevance of abnormal karyotype was further clarified by category-specific analysis, especially in SM-AHN (HR = 1.8). Though karyotype also had prognostic value in ASM (HR = 4.9) but not in ISM or MCL, the researchers cautioned that the sample sizes of patients with ASM, ISM, or MCL were too small to draw definitive conclusions. Furthermore, multivariable analysis of patients with SM associated with a myeloid malignancy showed that the prognostic value of karyotype was overpowered by that of adverse mutations; abnormal karyotype and adverse mutations had a HR of 1.8 and 3.1, respectively.

The incidence of cytogenetic abnormalities in patients with SM was less than 10% in ISM and ASM but may have been greater than 25% for patients with SM-AHN, according to the researchers. They concluded, “The current study confirms the infrequent occurrence of cytogenetic abnormalities…although the additional observation regarding prognostic relevance requires validation in a larger study.”


1. Shah S, Pardanani, Elala YC, et al. Cytogenetic abnormalities in systemic mastocytosis: WHO subcategory-specific incidence and prognostic impact among 348 informative cases [published online August 28, 2018]. Am J Hematol. doi: 10.1002/ajh.25265