Survival characteristics of myelodysplastic syndrome with U2AF1-mutation and the clinical efficacy of arsenic-containing traditional Chinese medicine compound prescription

To explore the clinical characteristics of myelodysplastic syndrome (MDS) with U2 small nuclear RNA cofactor 1 (U2AF1) mutation in different age groups, as well as the efficacy and prognosis of an arsenic-containing traditional Chinese medicine (TCM) compound prescription (Qinghuang Capsules combined with Bushen Yijing Formula).

A retrospective analysis was conducted on the clinical data of patients with MDS who were hospitalized in the Hematology Department Ward of Xiyuan Hospital, China Academy of Chinese Medical Sciences, and received arsenic-containing TCM compound treatment from November 30, 2020, to September 30, 2023. Stratified by age, the U2AF1 mutation and wild-type groups aged < 65 years and ≥ 65 years were compared in terms of sex, TCM syndrome, World Health Organization classification, MDS Revised International Prognostic Score System (IPSS-R) score, blood routine indicators, serum lactate dehydrogenase content, nephroblastoma 1 (WT1) expression level, bone marrow puncture and biopsy indicators, and chromosomal prognostic grades, et al. Furthermore, the efficacy of arsenic-containing TCM compound were compared in the U2AF1 mutation and wild-type groups among different age groups, as well as the influence of age on the survival prognosis of MDS patients with U2AF1 mutation.

A total of 201 patients with MDS were included. 104 patients were under 65 years old, among whom 20 had U2AF1 mutation, and 84 had wild-type. Ninety-seven patients were aged 65 years or older, among whom 19 patients had the U2AF1 mutation and 78 had the wild-type. Among patients aged < 65 years, the U2AF1 mutation group had a higher proportion of male patients and very low-risk/low-risk patients with an IPSS-R score ≤ 3 (P < 0.05), a lower mean corpuscular volume (MCV) (P < 0.05), and a relatively higher proportion of peripheral blood cell line 1 reduction than the wild-type group (P < 0.05). Among patients aged ≥ 65 years, the MCV in the U2AF1 mutation group was lower (P < 0.05), and the expression level of the bone marrow WT1 gene and the proportion of patients with reticular fiber grade 4 were relatively higher than in the wild-type group (P < 0.05). The total effective rate of the arsenic-containing TCM compound for patients with U2AF1 mutation was 61.5% (24/39), and the total response rate was 30.8% (12/39). The total effective rate for the wild-type patients was 67.9% (110/162), and the total response rate was 29.6% (48/162). No significant difference was observed in the total effective and response rates. Kaplan-Meier survival analysis of 39 patients with U2AF1 mutation revealed that the median overall survival(mOS) of patients older than 65 years had not been reached. The 1-, 2-, and 3-year survival rates were 93.8%, 84.4%, and 84.4%, respectively. The mOS of the patients aged ≥ 65 years was 35 months (95% confidence interval [CI]: 7.559-62.441), and the 1-, 2-, and 3-year survival rates were 66.2%, 58.9%, and 29.4%, respectively. The mOS of patients in the aged ≥ 65 years group was significantly lower than that in the aged < 65 years group (P < 0.05), and no significant difference was observed in median progression-free survival between the two groups.

The U2AF1 mutation is closely associated with the clinical characteristics of MDS. However, age and the presence of U2AF1 mutation have no significant effect on the total effective and response rates of arsenic-containing TCM compound. Age is a significant factor influencing the prognosis of patients with MDS with U2AF1 mutation. Patients aged 65 years or older have a shorter survival time than those younger than 65 years.