Somatic mutations and the efficacy of immunosuppressive therapy in severe/very severe aplastic anemia and transfusion-dependent nonsevere aplastic anemia.

This study aimed to assess the prevalence of somatic mutations (SMs) in severe/very severe aplastic anemia (V/SAA) and transfusion-dependent nonsevere aplastic anemia (TD-NSAA) prior to immunosuppressive therapy (IST) and their impact on treatment efficacy. Next-generation sequencing was used to analyze 114 hematopoiesis-related genes at disease onset in 312 patients. SMs were detected in 17.9% of cases, involving 25 genes, most commonly DNMT3A (14, 20.9%) and BCOR (9, 13.4%). SMs were more frequent in patients over 40 years old, predominantly with a single mutation of low variant allele frequency (< 20%). Patients with SM were older and had lower lymphocyte counts. SMs did not significantly influence hematologic responses at 3, 6, or 12 months, relapse, progression, death, survival, or failure-free survival (p > 0.05). Grouping patients by mutated genes revealed no significant differences in IST efficacy, though Group I (PIGA or BCOR/BCORL1) showed higher hematologic response rates in patients over 40 years of age. The cumulative incidence of clonal evolution was higher in Group II (DNMT3A, TET2, ASXL1, FAT1, or RUNX1), though not statistically significant. SMs in V/SAA and TD-NSAA were infrequent and did not affect IST outcomes or treatment decisions. However, the higher clonal evolution incidence in certain mutations warrants further research.