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极低剂量阿仑单抗在急性白血病移植中的药代动力学和临床活性。

Pharmacokinetics and clinical activity of very low-dose alemtuzumab in transplantation for acute leukemia.

机构信息

Department of Internal Medicine, Hematology Division, BMT Unit, University Hospital of Patras, Rio/Patras, Greece.

出版信息

Bone Marrow Transplant. 2011 Oct;46(10):1363-8. doi: 10.1038/bmt.2010.308. Epub 2010 Dec 20.

DOI:10.1038/bmt.2010.308
PMID:21170091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3191504/
Abstract

The optimal dose of in vivo-administrated alemtuzumab in the allogeneic transplantation setting has not been defined. We report our experience on 37 patients with high-risk diseases, mainly acute leukemia (AML 23, ALL 10 patients), who underwent sibling (49%) or unrelated (51%) PBSCT (35 patients), and received a total dose of only 10-20 mg Campath-1H as part of the conditioning, and post-transplant CYA without MTX. The neutrophil and especially the platelet engraftment were rapid. There were only two grade III-IV acute GvHD cases, which occurred in unrelated transplants in the Campath-10 cohort. Chronic GvHD developed in six cases (17%) and was limited to skin in five of them. After a median follow-up of 371 days (59-1191), 70% patients are alive and in CR (Karnofsky 100%), and 11 died (TRM n=6, relapse n=5). From the five patients relapsed, three were at advanced stage at transplant and four underwent sibling HCT with the higher (20 mg) alemtuzumab dose. With the 10 mg alemtuzumab schedule (5 mg/day at days -2 and -1) we achieve at day of transplantation low but still lymphotoxic alemtuzumab serum concentrations (176 ng/mL), whereas levels declined fast thereafter, and at engraftment nearly no Campath antibody remained in the patient's serum.

摘要

在同种异体移植环境中,体内给予阿仑单抗的最佳剂量尚未确定。我们报告了 37 例高危疾病患者的经验,主要为急性白血病(AML23 例,ALL10 例),他们接受了同胞(49%)或无关供体(51%)PBSCT(35 例),并仅接受了 10-20mg 总量的 Campath-1H 作为预处理的一部分,以及移植后无 MTX 的 CYA。中性粒细胞特别是血小板植入迅速。仅发生了两例 III-IV 级急性移植物抗宿主病,这两例均发生在 Campath-10 队列的无关移植中。6 例(17%)发生慢性移植物抗宿主病,其中 5 例局限于皮肤。中位随访 371 天(59-1191 天)后,70%的患者存活且处于完全缓解状态(Karnofsky100%),11 例死亡(TRM 例 6,复发例 5)。在 5 例复发的患者中,3 例在移植时处于晚期,4 例接受了同胞 HCT,并使用了更高剂量(20mg)的阿仑单抗。采用 10mg 阿仑单抗方案(-2 天和-1 天每天 5mg),我们在移植当天达到了较低但仍具有淋巴毒性的阿仑单抗血清浓度(176ng/mL),此后水平迅速下降,在植入时患者血清中几乎没有 Campath 抗体残留。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c47/3191504/2142b09a6767/bmt2010308f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c47/3191504/2142b09a6767/bmt2010308f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c47/3191504/2142b09a6767/bmt2010308f1.jpg

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