Hamour Iman M, Lyster Haifa S, Burke Margaret M, Rose Marlene L, Banner Nicholas R
Cardiology and Transplantation Unit, The Royal Brompton and Harefield NHS Trust, Harefield Hospital, Harefield, Middlesex, UK.
Transplantation. 2007 Mar 15;83(5):570-6. doi: 10.1097/01.tp.0000253883.52525.7c.
Mycophenolate mofetil (MMF) provides superior prophylaxis against acute rejection when compared with azathioprine (AZA) in heart and renal transplantation. However, it remains unclear whether this results in improved survival or reduced morbidity after heart transplantation.
In a sequential study, 240 cardiac transplant patients were treated with either MMF (n=119) or AZA (n=121) both in combination with cyclosporine and corticosteroids after rabbit antithymocyte globulin induction.
By protocol lower cyclosporine levels were targeted in the MMF group during the first year (e.g. 203+/-52 ng/mL MMF vs. 236+/-59 ng/mL AZA, P=0.0006 at 6 months). Patient survival at 1 year (82% MMF vs. 79% AZA, P=0.55) and at 3 years was similar in both groups. The cumulative probability of receiving antirejection treatment within 1 year was lower in the MMF group, as was biopsy-proven acute rejection with International Society of Heart and Lung Transplantation grade > or =3A (24% vs. 35%, P=0.03). The MMF group also had fewer episodes requiring cytolytic therapy (6% vs. 13%, P=0.04) and more patients had steroids withdrawn by 1 year (66% vs. 32%, P<0.001). Renal function was better in the MMF group with lower creatinine levels at 1 year (133+/-45 vs. 155+/-46 micromol/L, P=0.0004). Calculated creatinine clearance (Cockcroft and Gault formula) at 1 year was also better (MMF 74+/-32 mL/min vs. AZA 62+/-24 mL/min, P=0.004).
Our results suggest that immunosuppression with MMF rather than AZA may allow lower cyclosporine levels, better renal function, and increased steroid weaning at 1 year while also achieving better control of acute rejection.
与硫唑嘌呤(AZA)相比,霉酚酸酯(MMF)在心脏和肾移植中对急性排斥反应的预防效果更佳。然而,心脏移植后其是否能提高生存率或降低发病率仍不明确。
在一项序贯研究中,240例心脏移植患者在接受兔抗胸腺细胞球蛋白诱导治疗后,分别接受MMF(n = 119)或AZA(n = 121)治疗,并联合环孢素和皮质类固醇。
根据方案,MMF组在第一年的目标是较低的环孢素水平(例如,MMF组6个月时为203±52 ng/mL,AZA组为236±59 ng/mL,P = 0.0006)。两组在1年(MMF组82%,AZA组79%,P = 0.55)和3年时的患者生存率相似。MMF组在1年内接受抗排斥治疗的累积概率较低,经活检证实的国际心肺移植学会分级≥3A的急性排斥反应也较少(24%对35%,P = 0.03)。MMF组需要细胞溶解治疗的发作次数也较少(6%对13%,P = 0.04),到1年时有更多患者停用了类固醇(66%对32%,P<0.001)。MMF组的肾功能更好,1年时肌酐水平更低(133±45对155±46 μmol/L,P = 0.0004)。1年时计算的肌酐清除率(Cockcroft和Gault公式)也更好(MMF组74±32 mL/min,AZA组62±24 mL/min,P = 0.004)。
我们的结果表明,与AZA相比,使用MMF进行免疫抑制可能在1年时允许更低的环孢素水平、更好的肾功能、增加类固醇撤药,同时也能更好地控制急性排斥反应。