Pharmacologic Prevention of Acute Graft‐Versus‐Host Disease
Pharmacologic Prevention of Acute Graft‐Versus‐Host Disease
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DOI：
10.1002/9781118416426.ch81
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发表时间：
2009-03
期刊：
影响因子：
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通讯作者：
N. Chao;K. Sullivan
中科院分区：
文献类型：
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作者：
N. Chao;K. Sullivan
早期人类同种异体骨髓移植通常并发移植物抗宿主病（GVHD）。本章主要集中在最常用的药物免疫抑制或免疫调节GVHD。它讨论了发病机制，同种异体反应性，和预测因素作为目标的药物在预防GVHD。非特异性免疫抑制药物皮质类固醇已与其他免疫抑制剂联合用于预防GVHD，但最常用作治疗已建立的GVHD的一线治疗。在细胞水平，MTX通过抑制二氢叶酸还原酶（DHFR）发挥其细胞毒性作用。甲氨蝶呤（MTX）是1948年引入用于治疗急性白血病的叶酸拮抗剂氨基蝶呤的类似物。特异性T细胞免疫抑制药物环孢素（CSP）是一种由11个氨基酸组成的中性疏水性环状肽。他克莫司是一种从土壤真菌Streptomyces tsukubaensis中提取的大环内酯类抗生素，具有类似的选择性免疫抑制活性。
Early human transplants of allogeneic marrow were often complicated by graft‐versus‐host disease (GVHD). This chapter focuses primarily on the most frequently used drugs for immunosuppression or immunomodulation for GVHD. It discusses the pathogenesis, alloreactivity, and the predictive factors utilized as targets for agents in the prevention of GVHD. Non‐specific immunosuppressive drugs Corticosteroids have been combined with other immunosuppressants in prophylaxis against GVHD, but is most frequently used as front‐line therapy in the treatment of established GVHD. At the cellular level, MTX exerts its cytotoxic effect by inhibiting dihydrofolate reductase (DHFR). Methotrexate (MTX) is an analog of aminopterin, the folic acid antagonist introduced in 1948 for the treatment of acute leukemia. Specific T‐cell immunosuppressive drugs Cyclosporine (CSP) is a neutral hydrophobic cyclic peptide composed of 11 amino acids. Tacrolimus is a macrolide antibiotic extracted from the soil fungus Streptomyces tsukubaensis and exhibit a similar selective immunosuppressive activity.