Improving the outcome of bone marrow transplantation by using CD52 monoclonal antibodies to prevent graft-versus-host disease and graft rejection
Improving the outcome of bone marrow transplantation by using CD52 monoclonal antibodies to prevent graft-versus-host disease and graft rejection
复制标题
DOI：
10.1182/blood.v92.12.4581.424k22_4581_4590
复制
发表时间：
1998-12-15
期刊：
影响因子：
20.3
通讯作者：
Waldmann, H
中科院分区：
文献类型：
--
作者：
Hale, G;Zhang, MJ;Waldmann, H
移植物抗宿主病(GVHD)是异基因骨髓移植后死亡和发病的主要原因，但可以通过去除供者骨髓中的T淋巴细胞来避免。然而，T细胞耗尽会增加移植排斥反应的风险。这项研究使用CD52单抗清除供者和受者骨髓中的T细胞，以防止移植物抗宿主病和排斥反应。对70例首次缓解的急性髓细胞白血病(AML)患者进行了人类白细胞抗原相合同胞移植的研究。在移植物输注前，用IgM(CamPath-1M)在体外耗尽移植物，用免疫球蛋白(CamPath-1G)在体内耗尽受体。未给予转位后免疫抑制。结果与两个对照组进行了比较：(1)50名患者接受了体内使用CamPath-1M但没有使用CamPath-1G的骨髓；(2)向国际骨髓移植注册中心(IBMTR)报告的459名患者接受了非枯竭移植物和传统的环孢素A(CyA)和甲氨蝶呤(MTX)预防GVHD。治疗组急性移植物抗宿主病的发生率为4%，而环磷酰胺/甲氨蝶呤组的急性移植物抗宿主病发生率为35%(P<；.001)。治疗组慢性移植物抗宿主病的发生率也非常低(3%比36%；P<；.001)。移植物排斥反应的问题在历史悠久的CamPath-1M组中经常出现(31%)，但在治疗组(6%)中基本上得到了解决。因此，治疗组的移植相关死亡率(5年时为15%)低于CyA/MTX组(26%；P=0.04)。在白血病复发风险方面，治疗组(5年时为30%)与CyA/MTX组(29%)差异不大。治疗组6个月存活率(92%比78%)优于环磷酰胺/甲氨蝶呤(78%)，5年存活率(62%比58%)和无白血病存活率(60%比52%)差异无统计学意义。我们的结论是，只要采取措施确保植入，T细胞耗竭是预防GVHD的有效策略。使用Camath-1G来耗尽残留的宿主淋巴细胞是一种简单而实用的方法。至少在急性髓细胞白血病中，GVHD的有益减少可以在不增加复发风险的情况下实现。(C)1998年由美国血液病学会主办。
Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity after allogeneic bone marrow transprantation, but can be avoided by removing T lymphocytes from the donor bone marrow. However, T-cell depletion increases the risk of graft rejection. This study examined the use of CD52 monoclonal antibodies to eliminate T cells from both donor marrow and recipient to prevent both GVHD and rejection. Seventy patients receiving HLA-identical sibling transplants for acute myelogenous leukemia (AML) in first remission were studied. An IgM (CAMPATH-1M) was used for in vitro depletion of the graft and an IgG (CAMPATH-1G) for in vivo depletion of the recipient before graft infusion. No posttransprant immunosuppression was given. Results were compared with two control groups: (1) 50 patients who received bone marrow depleted with CAMPATH-1M, but no CAMPATH-1G in vivo; and (2) 459 patients reported to the international Bone Marrow Transplant Registry (IBMTR) who received nondepleted grafts and conventional GVHD prophylaxis with cyclosporin A (CyA) and methotrexate (MTX). The incidence of acute GVHD was 4% in the treatment group compared with 35% in the CyA/MTX group (P < .001). Chronic GVHD was also exceptionally low in the treatment group (3% v 36%; P < .001). The problem of graft rejection, which had been frequent in the historic CAMPATH-1M group (31%), was largely overcome in the treatment group (6%). Thus, transplant-related mortality of the treatment group (15% at 5 years) was lower than for the CyA/MTX group (26%; P = .04). There was little difference in the risk of leukemia relapse between the treatment group (30% at 5 years) and the CyA/MTX group (29%). Survival of the treatment group at 6 months was better than the CyA/MTX group (92% v 78%), although at 5 years the difference was not significant (62% v 58%) and neither was the difference in leukemia-free survival (60% v 52%). We conclude that T-cell depletion is a useful strategy to prevent GVHD, provided that measures are taken to ensure engraftment. Using CAMPATH-1G to deplete residual host lymphocytes is a simple and practical method to do this. At least in AML, the beneficial reduction in GVHD can be achieved without an increased risk of relapse. (C) 1998 by The American Society of Hematology.