TRANSFUSION TRIAL TO PREVENT PLATELET ALLOIMMUNIZATION

这项提案的主要目标是评估使用 去白细胞血液制品和/或8-甲氧补骨脂素(8-MOP)和UV-A 预先处理随机供者血小板(RDP)以防止原发 同种异体免疫和研究人类白细胞抗原配型与随机配型 单一供者血小板和红细胞防止广泛致敏 有过同种异体免疫史的患者。慢性阻塞性肺疾病患者的区别 而没有事先的同种免疫是至关重要的，因为它们的不同 对输血反应的免疫学行为。之前 致敏作用将由常规的细胞毒性和流量决定。 细胞学。对于第一个目标，新免疫的非同种免疫患者 确诊的急性非淋巴细胞白血病将随机分为3组 治疗组：1)A组仅接受去白细胞的RDP和 红血球。2)B组仅接受灭活白细胞的RDP 通过8-MOP、UV-A和去白细胞红细胞。3)C组将 接受常规RDP和红细胞作为对照。特别强调的是 基于对残留在白细胞中的白细胞进行准确的定量- 耗尽的产品，因此潜在的免疫原性阈值可以 已经成立了。一种实现低值水精确定量的新方法 描述了白细胞耗尽血液中的白细胞数量。 每周将通过淋巴细胞毒性和血流量来检测抗体。 细胞学。人类白细胞抗原或非人类白细胞抗原的特异性将由 用纯化的人类白细胞抗原中和抗体。对于第二个 目的：将既往有同种异体致敏反应的患者随机分为 2组。1)A组接受人类白细胞抗原相合的单一献血者血液 产品。2)B组随机接受单一献血者血液制品。 抗体滴度的变化将通过流式细胞仪和 小组淋巴细胞毒抗体反应性。追溯性交叉匹配 将进行检查以确定10W水平的抗供体抗体 持续引起不良的输血反应或可接受的增量 在他们在场的情况下仍然可以发生。拟议研究的结果 不仅使我们能够评估防止异体致敏的方法 但它们也将加深我们对白细胞作用的理解 在触发对人类白细胞抗原的体液免疫反应中。

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.