巴利昔单抗作为免疫诱导剂预防国人心脏移植术后早期急性排斥反应的疗效和安全性的观察

The safety and efficacy of basiliximab as induction agent in preventing early acute rejection in Chinese cardiac transplantation receipts

目的观察国人心脏移植用巴利昔单抗作为免疫诱导剂与传统的三联免疫抑制剂合用的耐受性和预防术后早期急性排斥反应的效果。方法心脏移植患者47例,男38例,女9例,平均年龄(44.9±13.4)岁,包括扩张型心肌病20例(42.5%),缺血性心肌病12例(25.5%),致右室心律失常性心肌病8例(17.0%),肥厚型心肌病2例(4.2%),心脏肿瘤2例(4.2%),瓣膜性心肌病1例(2.1%),高血压心脏病1例(2.1%),巨细胞性心肌炎1例(2.1%)。术前淋巴细胞群体反应抗体(PRA)>10%者4例,交叉配型均<5%。用巴利昔单抗诱导治疗20mg×2次。三联免疫抑制剂用法:术中给予甲基强的松龙500mg×2次,术后125mg每8h1次;拔除气管插管后给予强的松1mg.kg-1.d-1,以后每3天减量10mg,至总量10mg/d维持。环孢素A(CsA)于术后血肌酐<150μmol/L开始服用,剂量3～6mg.kg-1.d-1,分2次服用,血药谷值浓度维持在180～300ng/ml。术后3周作1次心内膜活检。霉酚酸酯(MMF)1.0～2.0mg/d,分2次服用。急性排斥反应分级按照国际心肺移植协会(ISHLT)的标准。巨细胞病毒感染的监测用PP65抗原血症试验,EB病毒感染用ELISA方法查抗体。结果47例患者全部存活。急性排斥反应分级结果:0级30(63.8%)人,ⅠA级11(23.4%)人,ⅠB级3(6.3%)人,Ⅱ级3(6.3%)人。MMF平均剂量(1.2±0.3)g/d。CsA于术后平均(3.4±2.1)d开始服用,平均累积剂量(4.1±1.2)mg.kg-1.d-1,平均谷值浓度(237.0±76.2)ng/ml。术后1个月内感染5人,但无巨细胞病毒和EB病毒感染。结论国人心脏移植用巴利昔单抗作为免疫诱导剂与传统的三联免疫抑制剂合用的耐受性良好,预防术后早期急性排斥反应有效。

Objective To investigate the safety and efficacy of basiliximab as induction agent in preventing early acute rejection post heart transplantation. Methods Basiliximab （20 mg, iv ） was administered one hour before and 4 days post operation to patients （ n = 47） underwent heart transplantation between June 2004 and Feb 2005 in our department. Intravenous methylprednisolone （500 mg at operation beginning and repeated immediately post operation, followed by 125 mg every 8 hours for the first day）. Prednison was then initiated at 1 mg·kg^-1·d^-1 tapered 10 mg every 3 days to 10 mg/d. Mycophenolate mofetil （MMF, 0. 5-1.0 g twice daily） was also administered post intubation, oral Cyclosporine A （CsA, 3 to 6 mg·kg^-1·d^-1 ） was prescribed after transplantation if serum creatinine was 〈 150 μmol/L. The dose of CsA was individually adjusted to achieve a target serum concentration of 180-300 ng/ml. Endomyocardial biopsies were performed 3 weeks （ 19.7 ±9. 6） d post heart transplantation. Biopsy specimens were graded according to the standardized criteria of the International Society for Heart and Lung Transplantation （ISHLT）. Echocardiograms were routinely performed weekly within the first 3 weeks post-operation. Results All 47 consecutive patients[ mean age （ 44. 9 ± 13.4 ） years, range 13-63 years, 38 men ] survived the operation and the underlying diseases was idiopathic cardiomyopathy （42. 5% ）, ischemic heart disease （25.5%）, arrhythmogenic fight ventricular cardiomyopathy （ 17. 0% ）, hypertrophic cardiomyopathy （4. 2% ） , heart tumor （4. 25% ） ,valve heart disease （2. 1% ） , hypertensive cardiomyopathy （2. 1% ） and giant cell myocarditis （2. 1% ）. There were 4 patients with pre-operation PRA 〉 10% and CDC was less than 5% in all patients. The grades of the acute rejection in biopsy specimens were as follow： Grade （G） 0 in30 （63.8%）,G ⅠA in 11（23.4%）,G ⅠB in 3 （6.3%） and GⅡ in3 （6.3%） patients. The average dose of MMF was （ 1.2 ± 0. 3 ） g/d. The initial time of receiving CsA was （ 3.4 ± 2. 1 ） day post operation. The average cumulative dose of CsA was （4. 1 ± 1.2） mg·kg^-1·d^-1 before endomyocardial biopsy. The average serum concentration of CsA was （237.0 ± 76.2） ng/ml. Left ventricular ejection fraction assessed by echocardiogram was normal in all patients within the first 3 weeks. Five patients suffered from respiratory infections and recovered post antibiotic and symptomatic therapies. Conclusion Basiliximab as induction agent in combination with conventional triple immunosuppressive therapy is safe and effective in preventing acute rejection in Chinese cardiac transplantation receipts.