Hematopoietic stem cell transplantation and immunosuppressive therapy: implications of clonal haematopoiesis

Aplastic anemia (AA) is a life-threatening bone marrow failure syndrome. The advent of next-generation sequencing (NGS) has shed light on the link between somatic mutations (SM) and the efficacy of immunosuppressive therapy (IST) in AA patients. However, the relationship between SM and hematopoietic stem cell transplantation (HSCT) has not been extensively explored. In this retrospective analysis, we examined 166 AA patients who received HSCT or IST at our institution between May 2019 and December 2023. NGS was conducted on 66 genes within bone marrow cells to investigate the correlation between SM and the prognosis and therapeutic response in AA patients, as well as to assess the impact of mutation types on HSCT outcomes. Clinical data were gathered from 166 AA patients, comprising 84 males and 82 females, with a median age of 32 years (ranging from 9 to 75 years). In our study, a total of 151 somatic mutations were identified across 84 patients (50.6%), with 42 patients (25.3%) presenting a single mutation and 26 patients (15.7%) harboring two mutations. The top five genes with the highest mutation frequency were BCOR/BCORL1 (12.6%), ASXL1 (8.6%), TET2 (6.6%), CEBPA (5.3%), and GATA2 (4.6%). We stratified patients into SM and No-SM groups based on the presence of mutations and further divided them into HSCT and IST groups to assess the influence of mutation types on treatment response and survival within and between these groups. The findings were as follows: 1.Patients in the HSCT group exhibited a higher treatment response (OR 85.9% vs. 68.4%, p < 0.05), although there was no significant difference in survival. 2.Patients with favorable mutations, such as PIGA and BCOR/BCORL1, experienced significantly improved response and survival compared to those with unfavorable mutations like ASXL1, DNMT3A, and TET2 (OR 93.7% vs. 72%, p < 0.05) (3-year OS 93.7% vs. 80%, p > 0.05). 3.The HSCT-Favorable group demonstrated superior response rates (OR 100% vs. 67.7%, p < 0.05) and longer survival (3-year OS 100% vs. 67.7%, p < 0.05) compared to the IST-Favorable group. This study underscores that AA patients carrying favorable mutations, particularly BCOR/BCORL1, tend to have a more robust response and better prognosis than those without mutations or those with unfavorable mutations, such as ASXL1/DNMT3A. These findings are especially pertinent to HSCT, highlighting the importance of NGS prior to initiating treatment.