The efficacy of immunosuppressive therapy with or without thrombopoietin receptor agonist in elderly patients with severe aplastic anemia.

Abstract

Old individuals are at a high risk of developing aplastic anemia, and immunosuppressive therapy (IST) based on anti-human T-lymphocyte immunoglobulin (ATG) and cyclosporine (CsA) is recommended for treating severe aplastic anemia (SAA). Adding the thrombopoietin receptor agonist (TPO-RA) to IST could improve hematologic responses in patients with SAA; however, limited data exist for elder patients. Here, we report on the efficacy and prognostic factors associated with porcine ATG and CsA with or without TPO-RA as first-line therapy in elderly patients with SAA. Porcine ATG was administered intravenously at a dose of 20 mg/kg/d for 5 days. CsA was administered orally, maintaining plasma trough concentrations of 150-250 µg/L. Eltrombopag was administered at a dose of 75-150 mg/day, and hetrombopag was administered orally at a dose of 15 mg/day. One hundred and twenty-eight SAA patients, with a median age of 63 (60-73) years old, were included in this study, including 44 very severe aplastic anemia (VSAA) patients. All patients completed the porcine ATG treatment, and mild serum sicknesses were observed. Ten patients (2 SAA patients and 8 VSAA patients) died within 3 months of ATG initiation (early death), with severe infections being the main cause of death. Sixty-nine patients achieved a hematologic response at 6 months, with an overall response (OR) rate of 53.9%. The complete hematologic response (CR) rate at 6 months was 18.0%. The addition of TPO-RA to IST did not improve the OR and CR rates; nonetheless, early death was significantly lower (0%) in patients receiving TPO-RA compared to those not receiving TPO-RA (12%). Patients were followed up for a median of 28 (0.1-117) months. The OR rate at the last follow-up was 62.5%, while the CR rate was 36.7%. One patient progressed to myelodysplastic syndrome, one to leukemia, one to hemolytic paroxysmal nocturnal hemoglobinuria, and five developed clonal chromosomal abnormalities. The 2-year overall survival rate and failure-free survival rate were 86.0% (95% CI: 78.1-91.3%) and 70.5% (95% CI: 61.3-77.9%), respectively. A baseline neutrophil count of < 0.05 × 10⁹/L was identified as an independent prognostic factor for early death. Age younger than 65 years, a baseline reticulocyte count of ≥ 7 × 10⁹/L, and the absence of fever before and within 3 months following ATG treatment were independent predictors for hematologic response at 6 months. In conclusion, treatment with porcine ATG and CsA was safe and effective in elderly patients with SAA. An extremely low baseline neutrophil count indicated a high risk of early death.