Somatic Mutations and Mutation Burden Predict Treatment Response and Survival in Adult Acquired Pure Red Cell Aplasia

Immunosuppressive therapy (IST) is the standard treatment for acquired pure red cell aplasia (aPRCA), but predictors of treatment response and long-term prognosis remain unclear. The clinical significance of somatic mutations in aPRCA is not fully understood. We retrospectively analyzed 69 adult aPRCA patients who underwent targeted next-generation sequencing of 69 genes associated with clonal hematopoiesis and myeloid neoplasms. Somatic mutations, T-cell receptor (TCR) gene rearrangements, treatment response at 6 months, overall survival (OS), and progression-free survival (PFS) were evaluated. Somatic mutations were detected in 62.3% of patients, mainly in epigenetic regulators like DNMT3A and TET2. Although mutations did not predict 6-month response to IST, higher mutation burden was associated with worse treatment outcomes (p = 0.01). TP53 and DNMT3A mutations were linked to shorter OS and PFS. Survival worsened with increasing mutation numbers, while mutations in TET2, ASXL1, GATA2, and STAT3 had no significant effect. TCR gene rearrangements were common in large granular lymphocyte leukemia-associated aPRCA but did not affect treatment response or survival. Somatic mutations are common in aPRCA and reflect clonal hematopoiesis. Mutation burden is a key determinant of IST response, while TP53 and DNMT3A mutations signal poorer long-term outcomes. Mutational profiling may improve risk stratification and guide personalized management.