Thrombopoietin Receptor Agonist Added to Standard Immunosuppressive Therapy for Hepatitis-Associated Aplastic Anemia

Background: Hepatitis-associated aplastic anemia (HAAA) is a rare variant of severe aplastic anemia (SAA) characterized with a syndrome of bone marrow failure that traditionally occurs within 6 months of an acute attack of hepatitis. HAAA is potentially lethal if left untreated. Management includes immunosuppression with antithymocyte globulin and cyclosporine and allogeneic hematopoietic stem cell transplantation. Addition of thrombopoietin receptor agonist (TPO-RA) improves both the overall response rate and complete response rate of SAA patients. Here, we tried to investigate the effect and adverse events of TPO-RA added to standard immunosuppressive therapy for HAAA.

Methods: A total of 17 HAAA patients who received ATG, cyclosporine and TPO-RA as first-line treatment between April 2019 and January 2024 were enrolled. 6 patients were SAA and 11 patients were very severe aplastic anemia (VSAA) according to the criteria of the International Aplastic Anemia Study Group. All TPO-RAs were added within 1 months after ATG initiation at dose of their standard administration respectively.

Results: Of all the patients, 8 received avatrombopag (2 with SAA and 6 with VSAA), 5 received eltrombopag (1 with SAA and 4 with VSAA), and 4 received hatrombopag (3 with SAA and 1 with VSAA). The median neutrophil count was 0.23 (range 0.01-0.78) ×10⁹/L, median reticulocyte count was 11 (range 1-40) ×10⁹/L, and median platelet count was 5 (range 1-12) ×10⁹/L. All patients achieved the end-point of 3 months and 16 patients achieved the end-point of 6 months. The rate of complete response was 11.8% and rate of overall response was 52.9% at 3 months. The rate of complete response at 6 months was 41.2% and rate of overall response was 70.6%. The overall response rate of patients treated with avatrombopag, eltrombopag and hatrombopag were 37.5% vs 40% vs 100%, and 62.5% vs 60% vs 100% at 3, 6 months after IST, respectively. The overall response rate at 3 months and 6 months were both higher than historical results of standard IST (ATG and cyclosporine, 34.1% at 3 months and 56.1% at 6 months). All TPO-RAs were safe, and there was no drug-related liver dysfunction. No patient discontinued TPO-RA due to adverse events.

Conclusions: In conclusion, the addition of TPO-RA to IST was safe and associated with higher overall response rate among patients with HAAA.

No relevant conflicts of interest to declare.