Thrombopoietin receptor agonists combined with intensive immunosuppressive therapy improve outcomes in elderly patients with severe aplastic anemia: A single-center retrospective study

Abstract Introduction: Intensive immunosuppressive therapy (IST) has significantly improved the prognosis of elderly patients with severe aplastic anemia (SAA) who are ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, approximately 30% of patients fail to respond to initial IST, and 10%–20% of responders experience relapse. Despite extensive research on SAA treatment efficacy, the potential benefit of combining thrombopoietin receptor agonists (TPO-RAs) with IST in elderly patients remains unclear. This study aimed to evaluate the impact of TPO-RA combined with IST on this population. Methods: We conducted a retrospective, single-center analysis of 32 elderly patients (aged ≥ 60 years) diagnosed with SAA or very severe aplastic anemia (VSAA) at Peking University Institute of Hematology between August 2014 and July 2025. Patients with congenital hematopoietic failure, myelodysplastic syndrome (MDS), or paroxysmal nocturnal hemoglobinuria (PNH) were excluded. Of the cohort, 25 received IST plus Hetrombopag (HPAG), including 13 with SAA and 12 with VSAA. The remaining 7 patients received ATG+CsA alone, including 6 with SAA and 1 with VSAA. Baseline characteristics, including age, gender, disease severity, and laboratory parameters, were comparable between groups. The median follow-up duration was 540 days (range: 19–2106 days). Results: A total of 32 elderly patients (13 males and 19 females) were included in this study. The cohort had a median age of 66 years (range: 61–78 years). The median time from diagnosis to treatment was comparable between the IST+HPAG group (31 days; range: 11–70 days) and the IST-alone group (30 days; range: 14–49 days). No significant differences were observed between the two groups in terms of age, sex, disease severity, neutrophil count, platelet count, reticulocyte count, ferritin levels, or PNH c lone presence. At 3 months, the cumulative response rates were 52.4% in the IST+HPAG group and 42.9% in the IST-alone group. By 6 months, the response rates had increased to 73.3% and 71.4%, with complete remission (CR) rates of 26.7% and 14.3%, respectively. At 12 months, the cumulative response rates had further improved to 92.9% and 85.7%, with CR rates of 35.7% and 33.3%, respectively. The 12-month overall survival (OS) rate was 83.3% (95% CI: 64.2%–92.7%). Univariate analysis of treatment response at 12 months revealed that higher Charlson Comorbidity Index (CCI) scores (P = 0.005) and longer time from diagnosis to treatment (P = 0.005) were associated with poorer response. However, no significant correlations were found with sex, pretreatment infection, neutropenia, or age. During follow-up, 5 patients died: 2 within 1 month, 2 within 2 months, and 1 due to COVID-19 infection at 4 months. Additionally, 1 patient relapsed after 3 years and 1 after 5 years, 1 progressed to MDS, and 1 remained alive despite treatment failure with alternative immunosuppressive therapy at 1 year. Conclusions: The addition of TPO-RA to IST demonstrated superior efficacy compared to IST alone in elderly patients with SAA or VSAA, yielding higher remission rates and improved clinical outcomes while maintaining favorable tolerability. These results underscore the potential of TPO-RA combination therapy in this patient population and warrant further investigation. Keywords: Severe aplastic anemia, thrombopoietin receptor agonists, immunosuppressive therapy, elderly patients