Hobbs J R, Williamson S, Chambers J D, James D C, Joshi R, Shaw P, Hugh-Jones K
Tokai J Exp Clin Med. 1985 Jun;10(2-3):207-14.
Matched sibling transplants enjoy over 95% survival of the grafting procedure, but are only available for 1:5 patients. A sibling sharing one genetic haplotype is today our next choice of donor (67% survival) faring better than other relatives (50% survival), providing total body irradiation (of the thymus) has been avoided. The latter, without increasing the attack rate (64%) of GvHD more than doubles the deaths (57% as against 27%) attributable to it. Rejection is avoided by (a) suicide of host responders to donor buffy coat; (b) Cyclosporin-A; (c) displacement induction; (d) a higher dose of marrow. Prevention of GvHD is essential, using either Cyclosporin-A or removing donor T-cells from marrow prior to infusion or, probably better, both. Autoblast immunisation should be further explored. Tolerization seems an active process, easier in the very young, and nonirradiation of the thymus is believed important. An assay to assess tolerization (to guide cessation of immunosuppressive measures) is badly needed. Selection of a donor whose lymphocytes can deal with intracellular infections of the host's fibroblasts is now possible. The required increased immunosuppressive measures appear to increase the risk of leukemic relapse, and perhaps should be first improved in the more cost-effective fields of inborn error transplants.
匹配的同胞移植的移植手术成功率超过95%,但仅适用于五分之一的患者。拥有一个遗传单倍型相同的同胞如今是我们的第二选择供者(成功率为67%),其情况优于其他亲属(成功率为50%),前提是避免了(对胸腺的)全身照射。如果不进行全身照射,移植物抗宿主病(GvHD)的发生率(64%)不会增加,但由此导致的死亡人数(57%,而之前为27%)却增加了一倍多。可通过以下方法避免排斥反应:(a)宿主对供者血沉棕黄层的反应细胞自杀;(b)使用环孢菌素A;(c)置换诱导;(d)增加骨髓剂量。预防移植物抗宿主病至关重要,可使用环孢菌素A,或在输注前从骨髓中去除供者T细胞,或者可能两者并用效果更好。自体细胞免疫应进一步探索。耐受似乎是一个活跃的过程,在幼儿中更容易实现,并且认为不照射胸腺很重要。迫切需要一种评估耐受情况的检测方法(以指导免疫抑制措施的停止)。现在有可能选择其淋巴细胞能够应对宿主成纤维细胞胞内感染的供者。所需增加的免疫抑制措施似乎会增加白血病复发的风险,或许应该首先在更具成本效益的先天性代谢缺陷移植领域进行改进。