Editor’s Note: The 13th Ludaopei Hematology Academic Conference, jointly organized by the Beijing Health Promotion Association and the Hongmian Tumor and Rare Disease Public Welfare Foundation, and hosted by the Beijing Ludaopei Hematology Research Institute, was held in Beijing on August 22–23, 2025. This high-level academic event brought together world-leading hematology experts to focus on hematopoietic stem cell transplantation, cellular therapy, and precision treatment of hematologic malignancies, providing a deep and comprehensive learning experience for more than a thousand participants. During the meeting, Professor Bing Han delivered an insightful lecture on “The Application of Thrombopoietin Receptor Agonists (TPO-RA) in Aplastic Anemia (AA).” Hematology Frontier summarized the key points to offer practical guidance and theoretical insights for optimizing clinical management strategies.
Guideline Recommendations and Treatment Principles
According to the Chinese Guidelines for the Diagnosis and Treatment of Aplastic Anemia (2022 Edition), the combination of immunosuppressive therapy (IST) with a thrombopoietin receptor agonist (TPO-RA) is now established as the first-line treatment for AA. For patients with severe aplastic anemia (SAA) or transfusion-dependent non-severe AA (TD-NSAA) who are ineligible for HSCT, the recommended first-line regimen is IST (ATG/ALG + CsA) combined with TPO-RA. For non-transfusion-dependent NSAA (NTD-NSAA), CsA combined with TPO-RA is recommended.
Patients receiving IST plus TPO-RA require regular follow-up to evaluate efficacy and adverse events. Key monitoring parameters include hematopoiesis, immune status, clonal evolution, and organ function.
Classes and Applications of Thrombopoietic Agents
Thrombopoietic agents include small-molecule nonpeptide TPO-RAs, peptide mimetics, and recombinant human TPO (rhTPO). Eltrombopag, romiplostim, and hetrombopag have been approved globally for AA treatment. In China, hetrombopag was approved in 2021 and eltrombopag in 2023 for SAA refractory to IST. Avatrombopag and lusutrombopag are not yet approved for AA worldwide.
Research on IST + TPO-RA as First-Line Therapy
Eltrombopag combined with IST has demonstrated significant benefits, including higher response rates, earlier hematologic recovery, and prolonged EFS and DFS. The RACE trial and EBMT-SAAWP follow-up confirmed improved outcomes with no significant increase in clonal evolution risk. Chinese studies further explored dose-response relationships, pharmacogenomic influences, and showed that combining eltrombopag with IST narrows the outcome gap between adult and pediatric patients.
Hetrombopag and Avatrombopag
Hetrombopag combined with IST significantly improves CR and ORR rates in SAA patients, as shown in multicenter Chinese phase III trials. Avatrombopag has also shown promising results, with ORR around 65% and CR of 35% in treatment-naïve SAA. Real-world data suggest significant benefit in elderly TD-NSAA patients.
Management of Refractory TD-NSAA
For transfusion-dependent NSAA patients refractory to IST, options include confirming diagnosis, alternative immunosuppressants, TPO-RAs, and HSCT for eligible younger patients. Studies show eltrombopag, hetrombopag, and avatrombopag remain effective and provide multilineage responses in this setting.
Switching Between TPO-RAs
For patients unresponsive to eltrombopag, high-dose romiplostim (20 μg/kg/week) has been shown to achieve hematologic responses in 70–76% of cases, with many achieving transfusion independence.
Early Mortality After IST
A study from Peking Union Medical College Hospital found that early mortality after IST in SAA/VSAA was 8.2%, mostly due to infection and intracranial hemorrhage. Risk factors include very severe AA, lymphocytes ≤0.5×10⁹/L, platelets ≤5×10⁹/L, and absence of antifungal prophylaxis.
Conclusion
The TPO-RA era has transformed the management of AA. IST + TPO-RA is the preferred first-line regimen for transplant-ineligible SAA and TD-NSAA patients. Multiple TPO-RAs offer robust efficacy and safety across various patient populations, including the elderly and refractory cases, broadening treatment options and improving outcomes.
Expert Profile
Professor Bing Han is Chief Physician and Doctoral Supervisor at the Department of Hematology, Peking Union Medical College Hospital, Head of the Red Cell Disorders Group, and core member of the International PNH Interest Group (IPIG). He serves in multiple national and international hematology committees, contributing extensively to the advancement of AA and red cell disorder research.
