MARS: Mutation-Adjusted Risk Score for Advanced Systemic Mastocytosis.

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Advanced systemic mastocytosis (AdvSM) is a rare hematologic neoplasm with significant morbidity and mortality.
• Accurate prognostic tools are crucial for effective treatment stratification and patient management.

Purpose of the Study:

• To develop and validate a risk score integrating clinical and mutation characteristics for patients with AdvSM.
• To improve the prediction of overall survival (OS) and leukemia-free survival (LFS) in AdvSM.

Main Methods:

• A Cox multivariable model was used to identify predictors of OS in 383 AdvSM patients from a German registry and international centers.
• Key variables included age, anemia, thrombocytopenia, and high molecular risk gene mutations (SRSF2, ASXL1, RUNX1).
• The mutation-adjusted risk score (MARS) was developed and validated in an independent cohort.

Main Results:

• The MARS identified three risk categories: low, intermediate, and high, with significantly different median OS (not reached, 3.9 years, 1.9 years, respectively).
• The MARS was independent of the WHO classification and accurately predicted LFS (P < .001).
• Leukemic transformation occurred in 16% of patients during a median follow-up of 2.2 years.

Conclusions:

• The MARS is a validated, five-parameter prognostic score for AdvSM.
• It effectively stratifies patients into distinct risk groups, independent of WHO classification.
• The MARS can potentially improve up-front treatment decisions for patients with AdvSM.