Apolipoprotein-a Is a Potential Prognosis Biomarker for Severe Aplastic Anemia Patients Treated with ATG-Based Immunosuppressive Therapy: A Single-Center Retrospective Study

Aplastic anemia (AA) is a bone marrow failure disorder characterized by pancytopenia with a risk of hemorrhage and infection. AA can be further divided into severe AA (SAA) and non-severe AA (NSAA) based on the severity of the disease. Anti-thymoglobulin (ATG)-based immunosuppressive therapy (IST) is the standard first-line management for SAA and very severe AA (VSAA) patients not eligible for hematopoietic stem cell transplantation (HSCT). Several studies identified the influencing factors on response and survival, including patient age, disease severity, absolute reticulocyte count and the interval between diagnosis and treatment. However, the prognosis cannot be improved if the patient exhibits poor response indicators when ATG-based IST is the only appropriate method. Adipocytes occupy the bone marrow of SAA, but the function of these cells is not yet clarified. Herein, we conducted this study aimed to explore the serum lipid changes during the ATG-based IST and identify the putative indicators that may predict the prognosis, thereby implying them as potential therapeutic target.

A total of 61 newly diagnosed SAA/VSAA patients aged between 10 and 60 years who received ATG-based IST were enrolled, and divided into IST-response (IST-R, n=40) and IST-non-response (IST-NR, n=21) groups based on the 9-month response effect. Differences were observed in blood lipids level, immunoglobulins and complements among groups after ATG-based IST. Significantly higher serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), apolipoprotein A (Apo-A) levels were detected in the IST-NR group than the IST-R group pretreatment (all P<0.05). After ATG-treatment, the Apo-A levels increased in the IST-R group while decreased drastically in the IST-NR group (Fig. A-F). Both groups showed decreased IgA after 3 months after IST, and the level in the IST-R group was much lower than that in the IST-NR group (P<0.05) (Fig. G-K). In order to predict the 9-month response early, we conducted a correlation analysis and found that the 9-month IST response had a moderate negative correlation with IgA level at 3 months (Spearman's r=-0.516, P=0.006) and a negative correlation to pretreatment Apo-A (Spearman's r=-0.380, P=0.004). Considering the dramatic changes between the IST-R and IST-NR groups, enrolled patients were respectively divided into two subgroup based on the cutoff value of Apo-A and IgA by receiver operating characteristic (ROC), and found that patients with lower Apo-A (<1.205 g/L) level pretreatment had a better event-free survival (EFS) (P=0.008)，but no differences were observed on OS (Fig. L-M). The patients with IgA level ≥1.72 g/L showed poorer EFS compared to those with IgA <1.72 g/L, although no statistically significant difference was noted (Fig. N-O).

In conclusion, the current study found that serum Apo-A is a potential prognosis biomarker for the newly diagnosed <60-year-old SAA/VSAA patients who received ATG-based IST, and the level of 3-month IgA can also be an indicator for 9-month IST response.

No relevant conflicts of interest to declare.