TRANSFUSION TRIAL TO PREVENT PLATELET ALLOIMMUNIZATION

预防血小板同种免疫的输血试验

• 批准号: 3553357
• 负责人: K J Kao
• 金额: $ 7.08万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3553357
• 关键词: MHC class II antigen; acute leukemia; antibody neutralization test; antileukocyte isoantibody; blood donor; blood transfusion; erythrocytes; flow cytometry; histocompatibility; human subject; immunogenetics; immunohematology; leukocyte antigen typing; leukocyte depletion therapy; lymphocyte; neoplasm /cancer therapy; platelets; psoralens; radiobiology; ultraviolet radiation; western blottings

The primary objectives of this proposal are to evaluate the use of leukocyte-depleted blood products and/or 8-methoxypsoralen (8-MOP) & UV-A pre-treated random donor platelets (RDP) to prevent primary alloimmunization and to investigate the use of HLA- matched vs random single donor platelets and red cells to prevent broad sensitization among patients with prior alloimmunization. the distinction of patients with and without prior alloimmunization is critical because of their different immunological behavior in response to blood transfusions. Prior sensitization will be determined by conventional cytotoxicity and by flow cytometry. for the first objective, non-alloimmunized patients with newly diagnosed acute non-lymphocytic leukemia will be randomized into 3 treatment groups: 1) Group A will receive only leukocyte-depleted RDP and red cells. 2) Group B will receive only RDP with leukocytes inactivated by 8-MOP and UV-A and leukocyte-depleted red cells. 3) Group C will receive regular RDP and red cells as control. Special emphasis will be made on accurate quantitation of leukocytes that remain in the leukocyte- depleted products so that a potentially immunogenic threshold can be established. A novel method to achieve precise quantitation of low numbers of white cells in leukocyte depleted blood is described. Antibodies will be measured weekly by lymphocytotoxicity and flow cytometry. HLA or non-HLA specificity will be determined by neutralization of antibody with purified HLA antigens. For the second objective, patients with prior allosensitization will be randomized into 2 groups. 1) Group A will receive HLA matched single donor blood products. 2) Group B will receive random single donor blood products. Changes of antibody titers will be measured by flow cytometry and by panel lymphocytotoxic antibody reactivity. Retrospective crossmatches will be performed to determine if 10W level anti-donor antibodies consistently induce poor transfusion responses or acceptable increments can still occur in their presence. The results of the proposed studies will not only allow us to evaluate methods to prevent allosensitization but they will also further our understanding about the role of leukocytes in triggering humoral immune responses to HLA antigens.

该提案的主要目标是评估 去白细胞血液制品和/或 8-甲氧基补骨脂素 (8-MOP) 和 UV-A 预先处理的随机捐赠血小板（RDP）以预防原发性 同种免疫并研究 HLA 匹配与随机的使用 单一供体血小板和红细胞，以防止广泛致敏 既往接受过同种免疫的患者。患者的区别 没有事先同种异体免疫是至关重要的，因为它们不同 对输血反应的免疫行为。事先的 致敏作用将通过常规细胞毒性和流量来确定 细胞计数术。对于第一个目标，非同种免疫患者新 诊断为急性非淋巴细胞白血病的患者将被随机分为 3 组 治疗组： 1) A 组仅接受去白细胞 RDP 治疗， 红细胞。 2) B组仅接受白细胞灭活的RDP 通过 8-MOP 和 UV-A 以及白细胞耗尽的红细胞。 3）C组将 接受常规 RDP 和红细胞作为对照。将特别强调 对白细胞中残留的白细胞进行准确定量 耗尽的产品，以便潜在的免疫原性阈值可以 已确立的。一种实现低浓度精确定量的新方法 描述了去除白细胞的血液中白细胞的数量。 每周通过淋巴细胞毒性和流量测量抗体 细胞计数术。 HLA 或非 HLA 特异性将由以下因素确定 用纯化的 HLA 抗原中和抗体。对于第二个 客观而言，先前接受过异敏治疗的患者将被随机分为 2组。 1) A组将接受HLA匹配的单一供血者血液 产品。 2) B组将随机接受单一捐献者的血液制品。 抗体滴度的变化将通过流式细胞术和 小组淋巴细胞毒性抗体反应性。回顾性交叉匹配 将进行以确定是否有10W水平的抗供体抗体 持续诱导不良的输血反应或可接受的增量 在他们面前仍然可能发生。拟议研究的结果 不仅使我们能够评估防止异体过敏的方法 但它们也将进一步加深我们对白细胞作用的理解 触发针对 HLA 抗原的体液免疫反应。