Chen Chun, Fang Jian-pei, Huang Shao-liang, Zhong Feng-yi
Department of Pediatrics, The Second Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Zhonghua Er Ke Za Zhi. 2006 Nov;44(11):841-4.
Aplastic anemia is characterized by bone marrow failure and marked reduction of white blood cells, red blood cells and platelets in peripheral blood. Clinical studies have shown that immunosuppressive therapy greatly prolonged the long-term survival of some patients with aplastic anemia. But in severe aplastic anemia (SAA) patients whose ANC was < 0.5 x 10(9)/L, platelets were < 20 x 10(9)/L, very low bone marrow proliferation and high death rate were observed. The present study aimed to evaluate the efficacy of immunosuppressive treatments with cyclosporine A (CSA) alone or CSA combined with antithymocyte globin (ATG) in children with acquired SAA.
Fifty-four cases with SAA were treated with immunosuppressive agents mentioned above in our department from Jan. 1997 to June 2003, 31 of the cases had treated with CSA combined with ATG. There were 18 cases with SAA type I and 13 cases with SAA type II in CSA combined with ATG group, and 13 cases had very severe aplastic anemia. The other 23 cases were treated with CSA alone (CSA group), 10 of these cases had SAA-I and 13 had SAA-II, and 5 cases had very severe aplastic anemia. The responsive rate, relapse, adverse reactions and event free survival (EFS) were compared between CSA combined with ATG group and CSA group.
The proportions of patients with different types of the disease and severity were comparable between the two groups. The responsive time of the CSA combined with ATG group and CSA group was 2.5 months and 3.5 months, respectively (P < 0.05), the responsive rate in two groups was 81% (25/31) and 52% (12/23), respectively (chi(2) = 4.962, P < 0.05). In 37 cases who were responsive to therapy, the relapse rate was 8% (2/25) and 50% (6/12) respectively (chi(C)(2) = 6.143, P < 0.05). There were no significant differences in adverse reactions to the immunosuppressive agents. All cases were followed-up for more than 1 year, and the event-free survival over one year in these two groups was 81% (25/31) and 52% (12/23), respectively. Forty-seven cases were followed-up for more than two years, and the event-free survival was 74% (20/27) and 50% (10/20), respectively (P < 0.01). Twelve cases were followed-up for over 5 years. There were no secondary tumor, myelodysplastic syndrome and other colony diseases.
The immunosuppressive therapies for acquired severe aplastic anemia in childhood were effective. The effect of CSA combined with ATG was better than that of CSA alone, and the relapse rate was lower with the combined treatment. However, the long-term effect needs longer follow-up studies to evaluate.
再生障碍性贫血的特征是骨髓衰竭以及外周血中白细胞、红细胞和血小板显著减少。临床研究表明，免疫抑制疗法可大大延长部分再生障碍性贫血患者的长期生存期。但在中性粒细胞绝对值（ANC）<0.5×10⁹/L、血小板<20×10⁹/L的重型再生障碍性贫血（SAA）患者中，观察到骨髓增殖极低且死亡率高。本研究旨在评估单独使用环孢素A（CSA）或CSA联合抗胸腺细胞球蛋白（ATG）对获得性SAA儿童进行免疫抑制治疗的疗效。
1997年1月至2003年6月，我科使用上述免疫抑制剂治疗54例SAA患者，其中31例接受CSA联合ATG治疗。CSA联合ATG组中，I型SAA 18例，II型SAA 13例，13例为极重型再生障碍性贫血。另外23例单独接受CSA治疗（CSA组），其中SAA-I 10例，SAA-II 13例，5例为极重型再生障碍性贫血。比较CSA联合ATG组与CSA组的缓解率、复发率、不良反应及无事件生存期（EFS）。
两组不同疾病类型及严重程度的患者比例具有可比性。CSA联合ATG组与CSA组的缓解时间分别为2.5个月和3.5个月（P<0.05），两组缓解率分别为81%（25/31）和52%（12/23）（χ²=4.962，P<0.05）。在37例对治疗有反应的患者中，复发率分别为8%（2/25）和50%（6/12）（校正χ²=6.143，P<0.05）。免疫抑制剂的不良反应无显著差异。所有病例均随访1年以上，两组1年无事件生存率分别为81%（25/31）和52%（12/23）。47例随访2年以上，无事件生存率分别为74%（20/27）和50%（10/20）（P<0.01）。12例随访5年以上。未出现继发性肿瘤、骨髓增生异常综合征及其他克隆性疾病。
儿童获得性重型再生障碍性贫血的免疫抑制治疗有效。CSA联合ATG的疗效优于单独使用CSA，联合治疗的复发率较低。然而，长期疗效需要更长时间的随访研究来评估。
