Clinical analysis on efficacy of rabbit anti-thymocyte globulin combined with cyclosporine in treatment of 128 children with aplastic anemia

Objective To evaluate efficacy, complications and influencing factors of children with aplastic anemia(AA)who were receiving rabbit anti-thymocyte globulin (rATG) combined with cyclosporine for immunosuppressive therapy (IST), and to explore optimal therapy for different clinical types of AA according to severity. Methods From 1st January 2006 to 1st February 2017, a total of 128 children who were diagnosed as AA by peripheral blood routine and bone marrow morphology and/or bone marrow pathology, and accepted rATG combined with cyclosporine in Department of Pediatric, Sun Yat-sen Memorial Hospital, Sun Yat-sen University. According to the clinical classification of the disease, the subjects were divided into non-severe aplastic anemia (NSAA) group (n=22), severe aplastic anemia (SAA) group (n=63), and very severe aplastic anemia (VSAA) group (n=43). The clinical data of the patients were retrospectively analyzed. The efficacy of the patients at 3, 6, 9 and 12 months after treatment and at the end of follow-up among 3 groups were evaluated by chi-square test. The treatment-related adverse reactions and prognosis were observed. Univariate analysis of different influencing factors, such as age, absolute value of neutrophils, platelet count, and reticulocyte were performed using the chi-square test. Statistically significant factors in the univariate analysis were included in the Cox proportional hazard regression model for multivariate analysis. Survival analysis was performed using the Kaplan-Meier method. The procedure of this study was accordance with the requirement of the revised World Medical Association Declaration of Helsinki in 2013. Informed consent was obtained from all guardians of participants. Results ① Of the 128 patients, 121 cases were evaluable, 5 cases were lost to follow-up, and 2 cases were early death. The complete remission (CR) rates at 3, 6, 9, and 12 months after treatment and at the end of follow-up were 5.0% (6/121), 14.9% (18/121), 16.5%(20/121), 28.9% (35/121) and 51.2% (62/121), respectively. The overall response rates were 33.9% (41/121), 38.9% (47/121), 49.6% (60/121), 62.8% (76/121) and 65.3% (79/121) , respectively. The response rates at 3 and 6 months after treatment in the NSAA group were 63.6% (14/22) and 68.2% (15/22), which were significantly higher than those of 30.5% (18/59) and 39.0% (23/59) in SAA group, 22.5% (9/40) and 22.5% (9/40) in VSAA group, the former were statistically different from the latter two (χ2=11.416, 13.297, P=0.001, 0.05). ④ The lymphocyte count 0.05). Conclusions The treatment of rATG combined with cyclosporine in children with SAA and VSAA has a higher response rate and a lower incidence of serious complications, which can be used as first-line treatment in the absence of appropriate donors. The lymphocyte count<1.5×109/L, platelet count≥20×109/L, and decreased CD3+ CD4+ cell ratio might be predictors of good response to rATG combined with cyclosporine in the treatment of children with AA. Key words: Anemia, aplastic; Immunosuppressive agents; Child; Rabbit anti-thymocyte globulin