Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation:: a phase 1/2 study
Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation:: a phase 1/2 study
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DOI：
10.1016/s0140-6736(02)09413-8
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发表时间：
2002-07-13
期刊：
影响因子：
168.9
通讯作者：
Cavazzana-Calvo, M
中科院分区：
文献类型：
--
作者：
André-Schmutz, I;Le Deist, F;Cavazzana-Calvo, M
异体造血干细胞移植（HSCT）是许多血液系统恶性肿瘤和遗传性疾病的治疗选择。当用于移植的干细胞来自人类白细胞抗原匹配的非相关供体，或来自部分不匹配的相关供体时，移植物的离体t细胞耗损可以防止移植物抗宿主病的发展，但反过来导致免疫重建的延迟和机会性感染和白血病复发发生率的一致增加。我们的目标是使用一种旨在消除同种异体激活的供体T细胞的离体程序，选择性地将导致移植物抗宿主病的同种异体T细胞耗尽的T细胞注入与细胞表面活化抗原CD25反应的免疫毒素。方法：我们进行了一项1/2期研究，在第15天至第47天之间，将1-8x10(5)个同种异体T细胞/kg输注到15名患有获得性或先天性造血系统疾病并在第0天接受造血干细胞移植的儿童患者中。评估移植物抗宿主病的发生和免疫重建时间。未给予移植物抗宿主病治疗。16例手术中有12例记录的残余抗宿主异体反应小于1%。其他免疫应答12例保存同种异体清除程序。没有出现严重（大于II级）移植物抗宿主病的病例。在三名持续病毒感染的患者中发现了早期t细胞扩增的证据。特别的抗病毒反应，如强的细胞溶解活性，被注意到。我们的研究结果表明，即使在单倍体相同的情况下，T细胞的体外选择性耗损引起移植物抗宿主病也是有效和可行的。
Background Allogeneic haemopoietic stem-cell transplantation (HSCT) is the treatment of choice for many haemological malignancies and inherited disorders. When stem cells for transplantation come from a human leucocyte antigen matched unrelated donor, or from a partly mismatched related donor, ex-vivo T-cell depletion of the graft can prevent development of graft-versus-host disease, but lead in turn to a delay in immune reconstitution and a concordant increase in incidence of opportunistic infections and leukaemic relapses. We aimed to infuse T cells selectively depleted in allogeneic T cells that cause graft-versus-host disease using an ex-vivo procedure designed to eliminate alloactivated donor T cells, with an immunotoxin that reacts with a cell surface activation antigen, CD25.Methods We did a phase 1/2 study, in which 1-8x10(5) allodepleted T cells/kg were infused between days 15 and 47 into 15 paediatric patients who had acquired or congenital haemopoietic disorders and who received HSCT on day 0. Occurrence of graft-versus-host disease and time to immune reconstitution were assessed. No treatment for graft-versus-host disease was given.Findings Less than 1% residual anti-host alloreactivity was recorded in 12 of 16 procedures. Other immune responses were preserved by the allodepletion procedure in 12 cases. No cases of severe (greater than grade II) graft-versus-host disease arose. Evidence for early T-cell expansion was shown in three patients with continuing viral infections. Specific antiviral responses, such as strong cytolytic activity, were noted.Interpretation Our results show that ex-vivo selective depletion of T cells that cause graft-versus-host disease is efficient and feasible, even in haploidentical settings.