DONOR BONE MARROW AS A BIOLOGIC IMMUNOSUPPRESSIVE AGENT

供体骨髓作为生物免疫抑制剂

• 批准号: 2066411
• 负责人: ARNOLD G DIETHELM
• 金额: --
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2066411
• 关键词: bone marrow transplantation; cell mediated lymphocytolysis test; clinical trials; cooperative study; cryopreservation; genetic library; histocompatibility typing; homologous transplantation; human subject; human therapy evaluation; human tissue; immunosuppression; immunosuppressive antileukocyte serum; kidney transplantation; lymphocyte; mixed lymphocyte reaction test; polymerase chain reaction; postmortem; restriction fragment length polymorphism; southern blotting; statistics /biometry; transplantation immunology

Donor specific unresponsiveness to organ allografts remains an illusive goal in clinical cadaveric transplantation, as most successful experimental protocols for the production of antigen-specific immunosuppression require lengthy recipient pretreatment. The use of an induction course of anti-lymphocyte serum (ALS) beginning at the time of transplantation, followed by the transfusion to the recipient of donor specific bone marrow, has been shown to induce prolonged allograft survival in animals and is applicable in clinical cadaveric transplantation. Our preliminary data in humans suggests that the transfusion of cryopreserved cadaver bone marrow following a short course of ALS is safe and does not induce graft versus host disease or allograft rejection. Thus far, 57 patients have received cadaveric renal allografts and ALG followed by the transfusion of cryopreserved donor specific bone marrow. 54 patients have received the contralateral kidney and similar immunosuppression without the marrow transfusion and serve as controls. The median followup in both groups is 16 months, (range 2.5 to 33 months). The graft survival rate for the bone marrow group at 12 and 18 months is 90% (confidence limits (CL) 85-94) and 85% (CL78-90) respectively. In the control group the 12 and 18 month allograft survival rate was 71% (CL 63-78) and 67% (CL 58-74) respectively (p=0.007). Mixed lymphocyte culture analysis shows a trend to diminish donor specific responsiveness in the bone marrow group. Analysis of peripheral blood lymphocytes of marrow transfused patients indicate the persistence of chimerism in some patients at least one year following transfusion as demonstrated by polymerase chain reaction. We propose to expand this single center experience to a multicenter trial in which donor specific bone marrow will be transfused in a prospective randomized fashion to renal allograft recipients following an induction course of use of donor marrow transfusion may be adaptable to a variety of induction protocols.

供体特定的对器官同种异体移植的反应仍然是一种虚幻的 临床尸体移植的目标是最成功的实验 生产抗原特异性免疫抑制的方案需要 冗长的接受者预处理。 使用的归纳课程 抗淋巴细胞血清（ALS）从移植开始时， 然后输给供体特异性骨髓的接受者， 已证明可以诱导动物的长期同种异体移植存活，IS 适用于临床尸体移植。我们的初步数据 人类认为冷冻保存的尸体骨髓的输血 遵循短暂的ALS是安全的，并且不会引起移植 宿主疾病或同种异体移植排斥。 到目前为止，已有57名患者接受 尸体同种异体移植物和ALG随后输血 冷冻保存的供体特异性骨髓。 54例患者已收到 对侧肾脏和类似的免疫抑制，没有骨髓 输血并充当控制。 两组的中间跟进是 16个月（范围2.5至33个月）。 骨骼的移植生存率 12和18个月的骨髓组为90％（置信度限制（CL）85-94）和 分别为85％（CL78-90）。 在对照组中12个月和18个月 同种异体移植生存率分别为71％（CL 63-78）和67％（Cl 58-74） （p = 0.007）。混合淋巴细胞培养分析显示了趋势减少的趋势 骨髓组的供体特定响应能力。 分析 骨髓输血患者的外周血淋巴细胞表明 至少一年后，某些患者的嵌合持续存在 通过聚合酶链反应证明的输血。 我们建议 将这种单一中心体验扩展到捐助者的多中心试验 特定的骨髓将以前瞻性的随机方式输血 在捐助者使用过程后，肾脏同种异体移植者接受者 骨髓输血可能适应各种诱导方案。