Interim Results of a Multi-Center Observational Study of Current Treatment Patterns for Patients with Severe Aplastic Anemia (SAA), Very Severe Aplastic Anemia (VSAA) and Transfusion-Dependent Non-Severe Aplastic Anemia (TD-NSAA) in China
Authors: Zhang Feng-Kui , Zhu Xiao-Fan , He Hai-Long , Wang Shun-Qing , Tang Jing-Yan , Zhou Dao-Bin , Zhang Dong-Hua , Zhou Yu-Hong , Wu De-pei , Li Wei , Xia Ling-Hui , Zhu Huan-Ling , Liu Feng , Shi Hong-Xia , Zhang Xi , Zhou Fang , Hu Jian-Da , Fang Jian-Pei , Chen Xie-Qun , Ye Tie-Zhen , Liang Ying-Min , Jin Jie 
Published: October 2019

Abstract
Background
In China, the incidence of aplastic anemia (AA) is about 0.74/105, with 0.14/105 of severe aplastic anemia (SAA). Most of these SAA patients are treated in big medical centers or traditional Chinese medicine (TCM) hospitals, which could stand for the current practices in China. Despite the China Aplastic Anemia Consensus, published in 2010, recommended that the immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT) were the standard treatment for SAA, very severe aplastic anemia (VSAA) and transfusion-dependent non-severe aplastic anemia (TD-NSAA), the current treatment options for patients with these diseases are diverse, including antithymocyte globulin (ATG)/antilymphocyte globulin (ALG) + cyclosporin A (CsA), CSA + androgen, CSA or androgen alone, only supportive care, TCM, etc. This national disease registry study aimed to describe the current clinical practice and treatment patterns for SAA, VSAA and TD-NSAA patients in China and understand their IST patterns as well as the supportive care measures.
Methods
In this prospective, multi-center, observational study, adult or pediatric patients diagnosed as acquired aplastic anemia within 3 months and met the guideline criteria of SAA, VSAA or TD-NSAA were enrolled from October 2012 to April 2014. All enrolled patients will be followed at least for one year. Each subject will be visited every 3 months in the first year and every 6 months from the second year until the patients withdraw the ICF or study close. The main evaluation criteria is the treatment patterns of SAA, VSAA and TD-NSAA which will be specified as: IST (ATG + CsA, CsA + androgen, CsA and others), HSCT, TCM, androgen, supportive care and others. The response of SAA/VSAA and TD-NSAA after each treatment, and serious adverse events, will also be evaluated by the investigators. An interim analysis is planned when all patients have been enrolled (target N=350) and will focus on their baseline characteristics and first treatment choice. This study was sponsored by Sanofi.
Results
A total of 352 patients were enrolled at 29 sites in China (SAA 221 pts; VSAA 84 pts; TD-NSAA 47 pts). The median age was 21 years (range, 0-84) and 65.1% were adults. 51.7% were male and 71.6% had ECOG PS <2. The vast majority of enrolled patients (344/352 pts, 97.7%) had no previous AA-related history. The most common onset symptom at baseline was anemia (92.9%), followed by hemorrhage (72.2%), infection (56.8%) and others (3.4%). TD-NSAA patients had less infections than SAA or VSAA patients (25.5% vs. 57.9%/71.4%). Cytogenetic abnormality were detected in 6.1% of the 245 patients who received cytogenetic test at baseline. The analysis of the primary endpoint showed 74.1% and 4.3% of the total patients received IST and HSCT at baseline, respectively. Among the patients with IST treatment, the standard ATG + CsA treatment was only applied in 26.4% of them (SAA 25.5%; VSAA 42.4%; TD-NSAA 5.4%). The other IST regimens were CsA + androgen (31.0%), CsA (31.4%) and others (11.1%). Three different brands of ATG/ALG were used in patients with IST: Rabbit ATG (75.0%), ATG-Fresenius (2.1%) and ALG-Porcine (22.9%). TCM therapy were applied in 12.8% of the total patients and were more common in SAA/VSAA patients (15.8% & 10.7%, respectively) than in TD-NSAA patients (2.1%). 2.8% of the patients received androgen therapy alone at baseline. 8 patients (2.3%) had switched their treatment pattern within 3 months before the enrolment because of unsatisfying efficacy (5 pts) or personal reasons (3 pts). Supportive care was applied in 95.7% of the total patients. The supportive care measures included blood transfusion (97.9%), antibiotics (64.1%), hematopoietic growth factors (58.8%), protective isolation (46.6%), iron chelators (0.3%) and others (2.7%). When the study initiated, the first treatment choice for all patients were IST (74.1%), HSCT (3.4%) and others (22.4%). There were no substantial difference of the first treatment pattern among SAA, VSAA and TD-NSAA groups.
Conclusions
Chinese AA patients received diverse treatments in real life clinical practice. Based on this interim analysis, 74.1% of the SAA, VSAA and TD-NSAA patients in China received IST. But only 26.4% of them received the standard ATG + CsA therapy. TCM therapy still played a role in the treatment, especially for SAA and VSAA patients in China. Final results including efficacy and safety profiles will be reported later.

Disclosures
Off Label Use: Anti-thymocyte globulin-Fresenius is used as an immunosuppressive therapy for the treatment of aplastic anemia.