Li Hongmin, Fu Lingling, Yang Bixi, Chen Hui, Ma Jie, Wu Runhui
Department of Hematology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Hematologic Disease Laboratory, Hematology Center, Beijing, China.
Front Med (Lausanne). 2022 Mar 7;9:805197. doi: 10.3389/fmed.2022.805197. eCollection 2022.
The management of children with non-severe aplastic anemia (NSAA) is undefined and the efficacies and benefits of immunosuppressive therapy remain inconsistent. The study aimed to investigate the efficacy of Cyclosporine (CsA) monotherapy for pediatric NSAA.
Clinical data of children with NSAA who had been treated with CsA monotherapy at the outpatient department of Beijing Children's Hospital, Capital Medical University, National Children's Medical Center from January 2017 to March 2021 was collected retrospectively. Patients who had been treated <1 years until the end of follow-up were excluded. Transfusion-independent NSAA was further divided into moderate NSAA and mild NSAA according to the degree of cytopenia. Progression was defined as the development of transfusion-dependent AA or SAA and relapse was considered when treatment failed after initial response.
A total of 95 pediatric patients with NSAA were enrolled in this study with 49 (51.6%) patients confirmed as mild NSAA, 38 (40%) as moderate NSAA and 8 (8.4%) as transfusion-dependent NSAA. The median treatment time of CsA was 22 (12-44) months. The overall response rate (ORR) was 57.9%, with 30.5% CR and 27.4% PR. Unexpectedly, patients with mild NSAA acquired lowest ORR (46.9%), then patients with moderate NSAA (63.2%), while 8 patients who were transfusion-dependent all had an active response to CsA. The granulocyte and megakaryocyte response was 46.9 and 55.8% respectively, while the erythrocyte response rate was as low as 22.5%. Univariate analyses revealed that patients with lower platelet count and higher interleukin 10 level predict an active response to CsA while higher level of fetal hemoglobin (HbF) tended to be a negative factor. Data of Treg cells before and after 1 year's treatment was available in a total number of 40 patients. Paired comparison found that the percentage of Treg cells in CD4+ T cells was decreased after 1 year's treatment of CsA (6.78 ± 2.72 vs. 5.23 ± 2.06, = 0.001),both in responders and non-responders. The degree of decline in Treg cells between two distinctive response groups had no significant difference (>0.05). With a median follow-up time of 22 months, 10.9% of responders relapsed and maintained NSAA while 27.5% of non-responders progressed to SAA or became transfusion-dependent. The overall progression rate was 11.6%.
CsA monotherapy had heterogeneous effects in the treatment of children NSAA Treatment approaches should be hierarchical and individual in clinical. Patients with lower platelet count and higher interleukin 10 level predicted an active response to CsA. While higher level of fetal hemoglobin (HbF) tended to be a negative factor. The percentage of Treg cells in CD4+ T cells was decreased broadly after treatment.
非重度再生障碍性贫血（NSAA）患儿的治疗方法尚不明确，免疫抑制治疗的疗效和益处仍不一致。本研究旨在探讨环孢素（CsA）单药治疗小儿NSAA的疗效。
回顾性收集2017年1月至2021年3月在首都医科大学附属北京儿童医院、国家儿童医学中心门诊接受CsA单药治疗的NSAA患儿的临床资料。排除随访结束时治疗时间<1年的患者。根据血细胞减少程度，将非输血依赖型NSAA进一步分为中度NSAA和轻度NSAA。疾病进展定义为出现输血依赖型再生障碍性贫血（AA）或重型再生障碍性贫血（SAA），初始缓解后治疗失败则视为复发。
本研究共纳入95例小儿NSAA患者，其中49例（51.6%）确诊为轻度NSAA,38例（40%）为中度NSAA,8例（8.4%）为输血依赖型NSAA。CsA的中位治疗时间为22（12 - 44）个月。总缓解率（ORR）为57.9%，完全缓解（CR）率为30.5%，部分缓解（PR）率为27.4%。出乎意料的是，轻度NSAA患者的ORR最低（46.9%），其次是中度NSAA患者（63.2%），而8例输血依赖型患者对CsA均有积极反应。粒细胞和巨核细胞缓解率分别为46.9%和55.8%，而红细胞缓解率低至22.5%。单因素分析显示，血小板计数较低和白细胞介素10水平较高的患者对CsA有积极反应，而胎儿血红蛋白（HbF）水平较高往往是一个负面因素。共有40例患者提供了治疗1年后调节性T细胞（Treg）的数据。配对比较发现，CsA治疗1年后，无论是缓解者还是未缓解者，CD4+T细胞中Treg细胞的百分比均下降（6.78±2.72 vs.5.23±2.06，P = 0.001）。两个不同缓解组之间Treg细胞的下降程度无显著差异（P>0.05）。中位随访时间为22个月，10.9%的缓解者复发并维持NSAA，而27.5%的未缓解者进展为SAA或变为输血依赖型。总进展率为11.6%。
CsA单药治疗小儿NSAA的效果存在异质性，临床治疗方法应分级个体化。血小板计数较低和白细胞介素10水平较高的患者对CsA有积极反应。而胎儿血红蛋白（HbF）水平较高往往是一个负面因素。治疗后CD4+T细胞中Treg细胞的百分比普遍下降。
