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体外暴露于Campath-1G使T细胞耗竭可预防移植物抗宿主病。

T cell depletion by exposure to Campath-1G in vitro prevents graft-versus-host disease.

作者信息

Jacobs P, Wood L, Fullard L, Waldmann H, Hale G

机构信息

University of Cape Town Leukaemia Centre, Groote Schuur Hospital, S. Africa.

出版信息

Bone Marrow Transplant. 1994 Jun;13(6):763-9.

PMID:7920312
Abstract

Campath-1G is an immunosuppressive monoclonal antibody directed against human lymphocytes. Its effectiveness in preventing graft-versus-host disease (GVHD) by simple opsonisation of bone marrow T-cells has been studied in 36 consecutive allografts: in 17 for leukaemia, one for essential thrombocytosis and four for myeloma this was the sole means of GVHD prophylaxis. A further eight patients with aplastic anaemia received 3 months post-transplantation cyclosporin A (CsA) for this purpose whereas in the ninth and tenth the preparative regimen has been modified with this immunosuppressive agent now discontinued. Nucleated cells were harvested and after quantitative recovery of the mononuclear population on the Cobe 2997 separator they were exposed to 20 mg Campath-1G for 30 min at room temperature and then infused. Following standard conditioning, which included total lymphoid irradiation, the median days to reach 0.5 and 1.0 x 10(9)/l neutrophils were respectively 18 (range 9-34) and 28 (range 10-59); to 25 and 100 x 10(9)/l platelets the corresponding times were 17 days (range 5-32 days) and 27 days (range 13-127 days). In all, the day 14 trephine biopsy showed engraftment. At median follow-up of 20 months (range 5-44 months) only one patient has developed possible grade I cutaneous GVHD that responded promptly to corticosteroids: no chronic GVHD or CMV pneumonitis has been encountered. Of those with haematological malignancy transplanted in remission only two with acute leukaemia have relapsed. In aplastic anaemia graft loss initially occurred but this has been overcome by adding Campath-1G in vivo and omitting CsA.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

Campath-1G是一种针对人类淋巴细胞的免疫抑制性单克隆抗体。通过对36例连续同种异体移植研究了其通过简单调理骨髓T细胞来预防移植物抗宿主病(GVHD)的有效性:其中17例用于白血病,1例用于原发性血小板增多症,4例用于骨髓瘤,这是预防GVHD的唯一手段。另外8例再生障碍性贫血患者移植后3个月为此接受环孢素A(CsA)治疗,而第9例和第10例患者的预处理方案已进行调整,目前已停用这种免疫抑制剂。采集有核细胞,在Cobe 2997分离器上定量回收单核细胞群体后,将其在室温下与20 mg Campath-1G接触30分钟,然后进行输注。在包括全身淋巴照射的标准预处理后,中性粒细胞达到0.5和1.0×10⁹/L的中位天数分别为18天(范围9 - 34天)和28天(范围10 - 59天);血小板达到25和100×10⁹/L的相应时间分别为17天(范围5 - 32天)和27天(范围13 - 127天)。总体而言,第14天的骨髓活检显示植入成功。在中位随访20个月(范围5 - 44个月)时,仅1例患者出现可能的I级皮肤GVHD,对皮质类固醇迅速产生反应:未遇到慢性GVHD或CMV肺炎。在缓解期移植的血液系统恶性肿瘤患者中,只有2例急性白血病患者复发。再生障碍性贫血患者最初出现移植失败,但通过在体内添加Campath-1G并省略CsA已克服此问题。(摘要截取自250字)

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