CAMPATH-1 antibodies in stem-cell transplantation.
CAMPATH-1 antibodies in stem-cell transplantation.
复制标题
干细胞移植中的 CAMPATH-1 抗体。
DOI：
10.1080/146532401753173981
复制
发表时间：
2001
期刊：
影响因子：
4.5
通讯作者：
H. Waldmann
中科院分区：
文献类型：
--
作者：
G. Hale;S. Cobbold;N. Novitzky;D. Bunjes;R. Willemze;H. Prentice;D. Milligan;S. Mackinnon;H. Waldmann
背景
CAMPATH-1 (CD52) Abs 已用于干细胞移植，以预防 GvHD 和移植物排斥。通过去除供体和受体的 T 淋巴细胞，可以有效预防这些并发症。然而，供体淋巴细胞可能有助于抗白血病作用，而淋巴细胞耗竭可能会加剧免疫重建问题。 GvHD 风险与宿主抗移植物反应、复发和感染之间存在良好的平衡。
方法
4264 名患者的临床结果报告给中央登记处，并通过单变量和多变量方法进行分析，以确定最佳方案。测试了各种淋巴细胞去除方案，使用 CAMPATH-1M (IgM) 加补体或 CAMPATH-1G (IgG2b) 离体治疗供体 BM，并使用 CAMPATH-1G 体内治疗受体。人源化抗体 CAMPATH-1H 最近取代了 CAMPATH-1G。召开了临床合作者会议来讨论结果并回顾各个中心的经验。
结果
人们的兴趣集中在使用动员的 PBSC 进行移植以及使用降低强度的预处理方案（“迷你”或“非对应清髓”移植）。这些方法在未来可能会变得越来越重要，并将允许移植手术用于相对年龄较大的患者。 CAMPATH-1G 或 CAMPATH-1H 的使用与 GvHD 或排斥反应的低发生率相关，尽管存在一些差异，可能与人源化抗体的半衰期较长有关。移植后 CYA 出现了意想不到且明显矛盾的效果——它似乎降低了 6 个月后死于感染的风险。尽管部分益处可以通过 GvHD 的减少来解释，但当 GvHD 或移植物排斥的患者被排除在分析之外时，效果仍然很明显。
讨论
CAMPATH-1H 似乎在预防移植物排斥和 GvHD 方面具有有用的作用，特别是对于这些并发症高风险的患者。它同样可以通过与输注的干细胞混合或在移植前施用于患者来使用。未来的研究将寻求了解 CYA 效应的机制并提高免疫重建的质量。
BACKGROUND
CAMPATH-1 (CD52) Abs have been used in stem-cell transplants for the prevention of GvHD and graft rejection. These complications can effectively be prevented by depletion of T lymphocytes from both donor and recipient. However, donor lymphocytes might contribute an anti-leukemia effect and lymphocyte depletion may exacerbate problems with immune reconstitution. There is a fine balance between the risks of GvHD and host-versus-graft reactions, relapse and infection.
METHODS
Clinical outcomes for 4264 patients were reported to a central registry and analyzed by univariate and multivariate methods to determine the superior protocols. Various protocols of lymphocyte depletion were tested, using either CAMPATH-1M (IgM) plus complement or CAMPATH-1G (IgG2b) to treat the donor BM ex vivo and CAMPATH-1G in vivo to treat the recipient. The humanized antibody CAMPATH-1H has recently replaced CAMPATH-1G. A meeting of the clinical collaborators was convened to discuss the results and to review the experiences of individual centers.
RESULTS
Interest focused on the use of mobilized PBSC for transplantation and on the use of reduced-intensity conditioning regimens ('mini' or 'non-Correspondence myeloablative' transplants). These approaches are likely to become increasingly important in the future and will allow transplant procedures to be used for relatively older patients. The use of CAMPATH-1G or CAMPATH-1H was associated with a low incidence of GvHD or rejection, though there were some differences that might be related to the longer half-life of the humanized antibody. An unexpected and apparently paradoxical effect of post-transplant CYA was observed - it appeared to reduce the risk of dying from infection after 6 months. Although part of the benefit could be explained by a reduction in GvHD, the effect was still evident when patients with GvHD or graft rejection were excluded from analysis.
DISCUSSION
CAMPATH-1H appears to have a useful role in the prevention of graft rejection and GvHD, particularly in patients who are at high risk of these complications. It can equally well be used by admixture with the infused stem cells, or by administration to the patient prior to the transplant. Future studies will seek to understand the mechanism of the CYA effect and to improve the quality of immune reconstitution.
影响因子：
20.3
作者：
Hale, G;Zhang, MJ;Waldmann, H
通讯作者：
Waldmann, H