TRANSFUSION TRIAL TO PREVENT PLATELET ALLOIMMUNIZATION

预防血小板同种免疫的输血试验

• 批准号: 3553339
• 负责人: Jeffrey McCullough
• 金额: $ 21.37万
• 依托单位: UNIVERSITY OF MINNESOTA
• 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 1994-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3553339
• 关键词: acute leukemia; antileukocyte isoantibody; blood donor; blood tests; cell mediated lymphocytolysis test; cellular immunity; clinical trials; diagnosis design /evaluation; disease /disorder prevention /control; enzyme linked immunosorbent assay; histocompatibility; histocompatibility antigens; human subject; immune adherence reaction; immunofluorescence technique; immunosuppression; leukocyte depletion therapy; monoclonal antibody; platelet disorder; platelet transfusion; restraint

Alloimmunization is one of the major causes of refractoriness associated with platelet transfusion therapy. This can lead to significant morbidity and morality. Management of platelet refractoriness often is not effective; thus, prevention of platelet refractoriness is preferable. Several approaches have been attempted to reduce alloimmunization to platelet transfusion including use of: HLA matched platelets, single donor platelets, leukocyte-poor platelets, and immunosuppressive therapies, such as treatment of recipients with cyclosporine or transfusion of platelets treated with ultraviolet irradiation. Although HLA class I antibodies are frequently implicated as a cause of platelet refractoriness, they do not account for poor platelet responses in all alloimmunized patients. Only a relatively minor role has been ascribed to platelet-specific and/or drug-dependent antibodies in platelet refractoriness and no systematic study has investigated their potential role in this problem. The discovery in 1988 of new platelet alloantigens, such as Br a and Bak b, and the recent association of amphotericin B and vancomycin, with platelet refractoriness strongly suggest the need for a comprehensive test to analyze serum from refractory patients for all possible anti-platelet antibodies. Therefore, an investigation is proposed to reduce the incidence of alloimmunization and subsequent platelet refractoriness by reducing the number of donor exposures through use of single donor platelets and red cells that have been depleted of leukocytes. Twenty- four patients with newly diagnosed ANLL will be entered yearly in the randomized trial. It is further proposed to develop a sensitive and specific laboratory test to detect platelet refractoriness due to alloimmunization. The assays to be used include monoclonal antibody- specific antigen capture ELISA, immunofluorescence, protein A rosette formation, 51 Cr release and lymphocytotoxicity.

同种免疫是引起相关难治性的主要原因之一 并配合血小板输注治疗。 这可能会导致重大 病态和道德。 血小板不应期的管理通常是 没有效果；因此，预防血小板不应期是 更可取。 已尝试多种方法来减少 血小板输注的同种免疫包括使用： HLA 匹配 血小板、单一供体血小板、贫白细胞血小板和 免疫抑制疗法，例如接受者的治疗 环孢素或输注经紫外线处理的血小板 辐照。 尽管 HLA I 类抗体经常与 作为血小板难治性的一个原因，它们不能解释不良 所有同种免疫患者的血小板反应。 只有一个相对 次要作用被归因于血小板特异性和/或药物依赖性 抗体在血小板不应期中的作用，目前尚无系统研究 研究了它们在这个问题中的潜在作用。 这一发现在 1988年新的血小板同种抗原，如Br a和Bak b，以及 最近两性霉素 B 和万古霉素与血小板的关联 耐火度强烈表明需要进行全面测试 分析难治性患者的血清中所有可能的抗血小板药物 抗体。 因此，建议进行一项调查以减少 同种免疫和随后的血小板不应性的发生率 通过使用单一捐赠者减少捐赠者暴露的数量 已耗尽白细胞的血小板和红细胞。 二十- 每年将有四名新诊断的 ANLL 患者进入 随机试验。 进一步建议开发一个敏感且 用于检测血小板不应性的特定实验室测试 同种免疫。 要使用的测定包括单克隆抗体- 特异性抗原捕获 ELISA、免疫荧光、蛋白 A 玫瑰花结 形成、 51 Cr 释放和淋巴细胞毒性。