社團法人臺灣臨床藥學會

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【綜合評述】心臟移植接受者抗體性排斥之治療
Antibody-Mediated Rejection in Heart Transplantation Recipients
抗體性排斥、心臟移植、Anti-CD20 單株抗體、Antibody-Mediated Rejection, Heart Transplantation, Rituximab
呂友敏You-Min Lu1 、張忠毅Chung-Yi Chang2 、常宏傳Hung-Chua Chang1 、黃劍銘Chien-Ming Huang1 、魏崢Jeng Wei*2
1振興醫院藥劑科 、2振興醫院心臟醫學中心
隨著免疫抑制劑的進步,細胞性排斥的預防與治療已有明顯成效,但抗體性排斥仍是未解決的問題,且會導致移植心臟的冠狀動脈血管病變,甚而造成移植心臟的損失。若能妥善處理抗體性排斥就可減少冠狀動脈血管病變的發生,進而改善心臟移植病人長期的存活率。臨床上,抗體性排斥較細胞性排斥更為嚴重,也較難治療,是預後不佳的指標,即便是無症狀的抗體性排斥也與冠狀動脈血管病變加速有關,且增加病人的死亡率,應謹慎處理。發生抗體性排斥包含許多複雜的步驟,針對這些過程可使用不同的作用機轉方式來治療,包含抑制T 細胞(例如antithymocyteglobulin)和B 細胞(例如rituximab)、阻斷殘餘抗體(例如intravenousimmunoglobulin)、清除漿細胞( 例如bortezomib) 及消除循環中的抗體 (doublefiltration plasmapheresis)。透過不同作用機轉藥品的併用會有較佳的治療效果。移植術後維持足量免疫抑制劑可預防抗體性排斥發生;一旦病人產生抗體性排斥,也有許多不同藥品可以使用,用藥期間有許多需監測的指標,才能在治療的同時減少副作用的發生。
 
With the developments of immunosuppressive agents in the recent years, there was significant progress in the treatments of cellular rejection after organ transplantation.However, antibody-mediated rejection (AMR) is still an unsolved issue, which may cause cardiac allograft vasculopathy (CAV) or even graft loss in the wake of heart transplants. Empirically, treating AMR in a proper way reduced the risk of CAV and further improved the long-term survival rate of heart transplant patients. AMR was more severe and hard-to-cure than cellular rejection. Clinically, patients with AMR showed poor prognosis. Even though AMR was asymptomatic, it still accelerated CAV and worsened the mortality rate of the aforementioned patients. The progression of AMR is comprised of complex steps. A potential combination of drugs could be directed against the targeted steps of the AMR progression. The treatment includes suppression of T cells (anti-thymocyte globulin) and B cells (rituximab), inhibition of residual antibodies (intravenous immunoglobulin), depletion of plasma cell (bortezomib) and elimination of circulating antibodies (double filtration plasmapheresis). After transplantation, immunosuppressive agents in sufficient dosage can prevent AMR.Once AMR occurs, there is the said combination of drugs pinpointing different AMR steps. Many parameters should be monitored to evaluate efficacy and prevent side effects earlier.
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