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在非清髓性预处理时代,阿仑单抗(Campath-1H)用于治疗淋巴系统恶性肿瘤?

Alemtuzumab (Campath-1H) for treatment of lymphoid malignancies in the age of nonmyeloablative conditioning?

作者信息

Hale G, Slavin S, Goldman J M, Mackinnon S, Giralt S, Waldmann H

机构信息

Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.

出版信息

Bone Marrow Transplant. 2002 Dec;30(12):797-804. doi: 10.1038/sj.bmt.1703733.

Abstract

The anti-CD52 (Campath-1) monoclonal antibodies (Mabs) have a substantial history of use for controlling graft-versus-host disease in allogeneic bone marrow transplantation. Now, with the availability of a humanised form, alemtuzumab (Campath-1H), and the demonstration that this agent can reduce the tumour burden in B-CLL, a new niche may be found - as a potentially curative agent in which its tumour purging ability in vivo combines with its role as a conditioning agent in nonmyeloablative transplantation. Review of the literature shows that alemtuzumab has unique advantages as a method of depleting malignant lymphocytes, including those in patients resistant to conventional chemotherapy. Alemtuzumab can also be used in BMT for depletion of normal T and B lymphocytes of both the recipient and donor for prevention of graft rejection and GVHD. It allows good stem cell recovery with resultant rapid engraftment, has a low risk of EBV-triggered secondary malignancy and does not interfere with blood stem cell mobilisation. As a method of eliminating the malignant clone in B-CLL, alemtuzumab has shown remarkable efficacy in heavily pre-treated patients, a number of whom have progressed to autologous or allogeneic transplantation. Efficacy data are shown within the context of other transplantation data for B-CLL. These results indicate that the combination of tumour-depleting and immunosuppressive properties of alemtuzumab should be explored, with the hope of providing improved treatment options for elderly patients with advanced B-CLL or indolent lymphoma whose prognosis is too poor currently to allow treatment with traditional regimens of high-dose myeloablative chemotherapy.

摘要

抗CD52(Campath-1)单克隆抗体(Mabs)在控制异基因骨髓移植中的移植物抗宿主病方面有大量的使用历史。现在,随着人源化形式的阿仑单抗(Campath-1H)的出现,以及该药物可降低B细胞慢性淋巴细胞白血病(B-CLL)肿瘤负荷的证明,可能会发现一个新的应用领域——作为一种潜在的治愈性药物,其体内肿瘤清除能力与其在非清髓性移植中作为预处理药物的作用相结合。文献综述表明,阿仑单抗作为一种清除恶性淋巴细胞的方法具有独特优势,包括对传统化疗耐药患者的恶性淋巴细胞。阿仑单抗还可用于骨髓移植,以清除受者和供者的正常T和B淋巴细胞,预防移植物排斥和移植物抗宿主病。它能使干细胞良好恢复并迅速植入,EB病毒引发继发性恶性肿瘤的风险低,且不干扰血液干细胞动员。作为一种清除B-CLL中恶性克隆的方法,阿仑单抗在经过大量预处理的患者中显示出显著疗效,其中许多患者已进展至自体或异基因移植。疗效数据在B-CLL的其他移植数据背景下展示。这些结果表明,应探索阿仑单抗的肿瘤清除和免疫抑制特性的联合应用,以期为晚期B-CLL或惰性淋巴瘤老年患者提供更好的治疗选择,这些患者目前的预后太差,无法接受传统的大剂量清髓性化疗方案治疗。

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