TRANSFUSION TRIAL TO PREVENT PLATELET ALLOIMMUNIZATION

预防血小板同种免疫的输血试验

• 批准号: 2220687
• 负责人: K J Kao
• 金额: $ 17.47万
• 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 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2220687
• 关键词: acute myelogenous leukemia; blood banks; blood donor; clinical trials; cooperative study; histocompatibility antigens; human subject; human therapy evaluation; leukocyte depletion therapy; medical complication; patient care management; platelet transfusion; plateletpheresis; radiation immunosuppression

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.

本提案的主要目的是评估 去白细胞血液制品和/或8-甲氧基补骨脂素（8-MOP）和UV-A 预处理的随机供体血小板（RDP），以防止原发性 同种异体免疫，并调查使用HLA匹配与随机 单供体血小板和红细胞，以防止广泛的过敏， 既往同种免疫的患者。患者的区别 并且没有预先的同种免疫是至关重要的，因为它们的不同 对输血的免疫反应。之前 将通过常规细胞毒性和流式细胞仪测定致敏性。 细胞仪对于第一个目标，非同种免疫的患者， 将确诊的急性非淋巴细胞白血病患者随机分为3组， 治疗组：1）A组将仅接受白细胞去除的RDP， 红细胞2)组B将仅接受白细胞灭活的RDP 8-MOP和UV-A以及白细胞减少的红细胞。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精确定量， 耗尽的产品，以便可以将潜在的免疫原性阈值 确立了习一种新的方法，以实现精确定量的低 描述了白细胞去除血液中白色细胞的数量。 将每周通过淋巴细胞毒性和流量测量抗体 细胞仪HLA或非HLA特异性将通过以下方式确定： 用纯化的HLA抗原中和抗体。第二 目的，既往有同种异体致敏反应的患者将被随机分配至 2组1)A组将接受HLA匹配的单一供体血液 产品. 2)B组将接受随机的单一供体血液制品。 抗体滴度的变化将通过流式细胞术和免疫组织化学法测量。 小组淋巴细胞毒性抗体反应性。回顾性交叉配血 以确定10 W水平的抗供体抗体 持续诱导不良输血反应或可接受的增量 仍然可以在他们在场的情况下发生。拟议研究的结果 不仅能让我们评估防止同种异体致敏的方法 但它们也将进一步加深我们对白细胞作用的理解 触发对HLA抗原的体液免疫反应。