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心脏移植后排斥反应的预防性治疗。兔抗胸腺细胞球蛋白与OKT3的比较。

Prophylactic therapy for rejection after cardiac transplantation. A comparison of rabbit antithymocyte globulin and OKT3.

作者信息

Kirklin J K, Bourge R C, White-Williams C, Naftel D C, Thomas F T, Thomas J M, Phillips M G

机构信息

University of Alabama, Department of Surgery, Birmingham 35294.

出版信息

J Thorac Cardiovasc Surg. 1990 Apr;99(4):716-24.

PMID:2108282
Abstract

The value of prophylactic monoclonal or polyclonal antibody therapy early after cardiac transplantation is controversial. Between Jan. 1, 1987, and July 1, 1988, 32 consecutive patients underwent cardiac transplantation (cyclosporine, azathioprine, and prednisone maintenance therapy) with either early prophylactic rabbit antithymocyte globulin (n = 17) or monoclonal OKT3 (Ortho Diagnostic Systems, Inc., Raritan, N.J.) (10 days) (n = 15). Follow-up was through Sept. 1, 1988, for morbid events and through Jan. 1, 1989, for survival. All patients (100%) survived the study period (follow-up of 6 to 24 months). The efficacy of rabbit antithymocyte globulin and OKT3 prophylaxis was similar regarding median time (days) to first rejection (16 versus 21 days, p = 0.5), number of rejection episodes during first 2 months (1.5 versus 1.3 days, p = 0.8), and freedom from rejection at 2 months (18% versus 27%, p = 0.8). Early infections were slightly less common in the rabbit antithymocyte globulin group than the OKT3 group (median time to first infection: 318 versus 250 days, p = 0.5; freedom from rejection at 2 months: 82% versus 64%, p = 0.21), although differences were likely due to chance. Cytomegalovirus syndrome was common, with one case of cytomegalovirus pneumonia. T-cell markers during OKT3 treatment did not predict subsequent rejection (within 2 weeks after OKT3) as assessed by mean T3-lymphocyte count during OKT3 use (p = 0.3) or T3-lymphocyte count during the last 3 days of OKT3 use (p = 0.4). Inferences: (1) Prophylactic rabbit antithymocyte globulin or OKT3 with triple-drug immunosuppression yields excellent intermediate survival after heart transplantation. (2) These protocols for rabbit antithymocyte globulin and OKT3 provide similar protection against early rejection with a relatively low risk of early infection. (3) T-cell markers do not predict early rejection after OKT3.

摘要

心脏移植术后早期预防性使用单克隆或多克隆抗体治疗的价值存在争议。在1987年1月1日至1988年7月1日期间,32例连续接受心脏移植的患者(采用环孢素、硫唑嘌呤和泼尼松维持治疗),其中17例早期预防性使用兔抗胸腺细胞球蛋白,15例早期预防性使用单克隆OKT3(Ortho诊断系统公司,新泽西州拉里坦)(使用10天)。随访至1988年9月1日观察发病情况,至1989年1月1日观察生存情况。所有患者(100%)均度过研究期(随访6至24个月)。兔抗胸腺细胞球蛋白和OKT3预防在首次排斥反应的中位时间(天)(16天对21天,p = 0.5)、前2个月内排斥反应发作次数(1.5次对1.3次,p = 0.8)以及2个月时无排斥反应率(18%对27%,p = 0.8)方面疗效相似。早期感染在兔抗胸腺细胞球蛋白组比OKT3组略少见(首次感染的中位时间:318天对250天,p = 0.5;2个月时无感染率:82%对64%,p = 0.21),不过差异可能是偶然因素所致。巨细胞病毒综合征常见,有1例巨细胞病毒肺炎。OKT3治疗期间的T细胞标志物不能预测随后的排斥反应(OKT3使用后2周内),通过OKT3使用期间的平均T3淋巴细胞计数评估(p = 0.3)或OKT3使用最后3天的T3淋巴细胞计数评估(p = 0.4)。结论:(1)在三联免疫抑制治疗基础上,预防性使用兔抗胸腺细胞球蛋白或OKT3可使心脏移植术后获得良好的中期生存率。(2)这些兔抗胸腺细胞球蛋白和OKT3方案在预防早期排斥反应方面提供相似的保护,且早期感染风险相对较低。(3)OKT3治疗后T细胞标志物不能预测早期排斥反应。

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