Anti-Human T Lymphocyte Porcine Immunoglobulin Combined with Cyclosporine As First-Line Immunosuppressive Therapy for Severe Aplastic Anemia in China: A Large Single-Center, 10-Year Retrospective Study

Abstract

Immunosuppressive therapy (IST) based on antithymoglobin (ATG) and cyclosporin (CsA) is the first-line treatment for severe aplastic anemia (SAA) patients who are ineligible for transplantation. Horse ATG is recommended as the standard preparation for first-line immune suppression in SAA, but it has been unavailable in China since the year 2000. The anti-human T lymphocyte porcine immunoglobulin (p-ATG, provided by Yujin Bio-Pharma Wuhan CNBG Co., Ltd., Wuhan, China) was made available in 1983 and approved for the treatment of aplastic anemia by the Sino Food and Drug Administration in 2004. It is a commonly used ATG preparation in IST for SAA in China since 2009. To date, only a few small retrospective cohort studies reported that p-ATG combined with cyclosporine (CsA) is a useful immunosuppressive regimen for SAA in China. This study retrospectively analyzed the data of 1023 consecutive patients diagnosed with SAA that aimed to evaluate the early hematologic response and long-term outcomes of this large cohort of patients with SAA who received p-ATG plus CsA as first-line therapy from 2010 to 2019. Patients received p-ATG for 5 consecutive days (day 1-5), at a dose of 20 mg/kg/day. And CsA was administered orally from day 1 of p-ATG treatment at two separate doses starting from 3 to 5 mg/kg/day and adjusted to maintain the trough concentration at 150-250 ng/ml and the peak concentration at 800-1000 ng/ml. One thousand twenty-three aplastic anemia were included in this study, with a median age of 24 (4-75) years, with 500 males and 473 females. The median follow-up was 57.2 months (3 days-137.5 months). Twenty-nine patients died within 3 months after IST, with an early death rate of 2.8% (29/1023); the median death time was 0.9 (0.1-2.9) months. The overall hematologic response rate (ORR) was 40.6% (415/1023) at 3 months, including 5.9% (60/1023) of patients with CR. The ORR was 53.2% (544/1023) at 6 months, including 13.5% with CR. Of the 395 patients who did not respond at 6 months, 26.1% (103/395) had an overall response at 12 months without any rescue treatment (10 had a CR, 93 had a PR). By the last follow-up, 9.2% (64/697) of the patients had experienced a relapse. The 5-year cumulative incidence of relapse was 9.0% [95% confidence interval (CI), 4.2 to 16.0%]. The 5-year cumulative incidence of clonal evolution was 4.5% (95% CI, 1.4 to 10.6%). The 5-year cumulative incidence of hPNH was 4.7% (95% CI, 1.2 to 12.4%). In patients with PNH clones at diagnosis, the 5-year cumulative incidence of hPNH was 22.5% (95% CI, 10.1 to 37.8%). The 5-year OS rate was 83.7% (95% CI, 81.1 to 86.0%). The 5-year event-free survival rate was 50.4% (95% CI, 47.1 to 53.5%). In conclusion, p-ATG combined with CsA for the treatment of AA is effective and safe, and p-ATG can be used as an alternative ATG preparation for the standard IST regimen in areas where h-ATG is not available.