Agarwal M B, Jijina Farah, Shah Sandip, Malhotra Pankaj, Damodar Sharat, Ross Cecil
Hematology Centre, Ghamat Lodge, 2nd Floor, Above ING Vaishya Bank, 804 A, Dr. B. Ambedkar Road, Dadar TT, Mumbai, India.
Department of Haematology, Seth GS Medical College & KEM Hospital, Ernest Borges Road, Parel, Mumbai, India.
Indian J Hematol Blood Transfus. 2015 Jun;31(2):174-9. doi: 10.1007/s12288-014-0423-z. Epub 2014 Jul 16.
To confirm the safety and efficacy of an indigenous equine antithymocyte globulin (eATG) along with cyclosporine in Indian subjects with acquired aplastic anaemia. Subjects >2 years old with acquired aplastic anaemia were enrolled at six hospitals between April 2011 and February 2013, after approval from respective Ethics Committees. Equine ATG at a dose of 40 mg/kg/day was infused for 4 days. Efficacy analysis defined a priori, was in subjects, who had completed eATG treatment and followed-up on day 90 and/or 180. Complete response (CR) was defined as-transfusion independent, haemoglobin ≥11 g/dL, absolute neutrophil count (ANC) >1.5 10(9)/L and platelet ≥150 10(9)/L; partial response (PR) was transfusion independent, haemoglobin ≥8 g/dL, ANC >0.5 10(9)/L and platelet ≥20 10(9)/L; non responders were transfusion dependent. Lymphocyte subsets (CD 2, 3, 4 and 8) in the blood were tested on days 0 (pre eATG infusion), 3, 5, 7, 14 and 21 after eATG. Of the 30 subjects (two children <12 years old) enrolled, 19 completed day 90 and 18 completed day 180 visit. Of the remaining 11 subjects, two died on days 12 and 45 due to septicaemia and pneumonia, one was withdrawn after the first dose of eATG due to jaundice and eight were lost to follow-up. The median age was 30 (9-58) years and weight was 57 (26-84) kg. On day 90, 12 of 30 subjects responded (CR 1, PR 11) and 15 of 30 (CR 2, PR 13) on day 180. The most common adverse event was fever related to eATG infusion. There were two serious adverse events (acute renal failure, febrile neutropenia) and both recovered with treatment. There were no unusual adverse events noted during the study period. Blood T lymphocytes showed a mean decrease of 91 % from baseline that recovered by day 21. We conclude that eATG is safe and in combination with cyclosporine showed overall response in 50 % of enrolled subjects. The trial was registered with the clinical trial registry-india (Registration no. CTRI/2012/03/002498).
为证实国产马抗胸腺细胞球蛋白（eATG）联合环孢素用于印度获得性再生障碍性贫血患者的安全性和有效性。2011年4月至2013年2月期间，经各伦理委员会批准，6家医院纳入了年龄大于2岁的获得性再生障碍性贫血患者。以40mg/kg/天的剂量静脉输注马抗胸腺细胞球蛋白，共4天。预先定义的疗效分析针对已完成eATG治疗并在第90天和/或第180天进行随访的患者。完全缓解（CR）定义为：无需输血，血红蛋白≥11g/dL，绝对中性粒细胞计数（ANC）>1.5×10⁹/L，血小板≥150×10⁹/L；部分缓解（PR）定义为：无需输血，血红蛋白≥8g/dL，ANC>0.5×10⁹/L，血小板≥20×10⁹/L；未缓解者依赖输血。在eATG治疗前第0天、治疗后第3、5、7、14和21天检测血液中的淋巴细胞亚群（CD2、3、4和8）。在纳入的30例患者（2例年龄<12岁儿童）中，19例完成了第90天随访，18例完成了第180天随访。其余11例患者中，2例因败血症和肺炎分别于第12天和第45天死亡，1例因黄疸在首次输注eATG后退出，8例失访。中位年龄为30（9 - 58）岁，体重为57（26 - 84）kg。第90天时，30例患者中有12例缓解（CR 1例，PR 11例）；第180天时，30例中有15例缓解（CR 2例，PR 13例）。最常见的不良事件是与eATG输注相关的发热。发生了2例严重不良事件（急性肾衰竭、发热性中性粒细胞减少症），均经治疗后康复。研究期间未发现异常不良事件。血液T淋巴细胞较基线平均减少91%，至第21天恢复。我们得出结论，eATG是安全的，与环孢素联合使用使50%的入组患者获得了总体缓解。该试验已在印度临床试验注册中心注册（注册号CTRI/2012/03/002498）。
