PROSPECTIVE STUDY TO DETERMINE THE EFFICACY AND SAFETY OF AZATHIOPRINE

这项研究的目的是确定硫唑嘌呤是否降低了儿童心脏手术时接受带瓣同种异体心脏移植的同种免疫反应。19名患者参加了这项研究，但有6名患者因各种原因退出了研究。在随机接受硫唑嘌呤治疗的那组患者中，有4名患者无法评估。一名患者在手术后24小时内死于低心输出量；一名患者因静脉穿刺法难以获得血液而应患者要求退出；两名患者被负责的外科医生撤回，一名患者是因为静脉注射抗生素反应的革兰氏阳性菌血症，一名患者是因为艰难梭菌阳性粪便。对照组中，1例患者术后4周死于低心输出量，1例患者因静脉穿刺术取血困难而退出。在目前登记的或已完成研究的13名患者中，6名接受硫唑嘌呤治疗，7名为对照组。到目前为止，治疗组和对照组在术后一个月或三个月的群体反应性抗体水平没有显著差异。接受硫唑嘌呤治疗的患者在三个月后需要减少剂量，因为肝脏转氨酶轻度升高和轻度中性粒细胞减少。减少剂量后，各项实验室指标均恢复正常。这项研究将确定更多的患者，直到有足够的人数可用来使研究人员能够确定该疗法是否降低了PRA的滴度。

The objective of this study is to determine if azathioprine reduces the alloimmune response in children who receive valved allografts at the time of pediatric heart surgery. Nineteen patients have been enrolled in this study, but six withdrew for various reasons. In the group randomized to receive azathioprine, four patients became inevaluable. One patient died within 24 hours of surgery from low cardiac output; one patient withdrew at the patient's request because of difficulty in obtaining blood by venipuncture; two patients were withdrawn by the responsible surgeon, one because of gram-positive bacteremia that responded to intravenous antibiotics, and one because of Clostridium difficile-positive stools. In the control groups, one patient died four weeks after surgery from low cardiac output, and one patient withdrew because of difficulty in obtaining blood by venipuncture. Of the thirteen patients currently enrolled, or who have completed the study, six were treated with azathioprine and seven were in the control group. To date, there is no significant difference in the level of panel-reactive antibodies between the treated group and the control group at the one-month point or at three months after surgery. Patients treated with azathioprine required dose reductions after three months because of mild liver elevations in transaminases and mild neutropenia. All laboratory values returned to normal after dose reduction. Additional patients will be ascertained for this study until a sufficient number are available to have statistical power enabling the investigators to determine if the therapy decreases the titer of PRA or not.