TRANSFUSION TRIAL TO PREVENT PLATELET ALLOIMMUNIZATION

本提案是为了响应RFA NIH 88-HL-12 B而提交的， 一个临床中心的研究，旨在确定实用的方法， 降低同种异体免疫的发生率和对 多次输血的急性脑梗死患者的血小板输注 非淋巴细胞白血病（ANLL）。 输血治疗 考虑因素包括使用：来自随机、单次 单采技术制备的供体;白细胞减少的血小板 浓缩物;和暴露于紫外线的血小板浓缩物 辐照 分配至以下患者的同种免疫发生率 将确定各种方案，并将其与 “对照组”用标准制备的浓缩血小板。 本研究为前瞻性、随机化和单盲研究。 患者 将根据人口统计学特征分配至特定研究组 协调人提供的信息，包括妊娠史等 中心 接受诱导治疗的新诊断为ANLL的患者 在密尔沃基的一些医院和密歇根大学进行的治疗， 位于麦迪逊的威斯康星州医院将有资格参加本研究。 血小板 输血将被规定用于治疗或预防 适应症，并将由东南血液中心准备 威斯康星州和美国红十字会血液服务-獾地区。 同种异体免疫和血小板输注无效将是 由临床和实验室参数确定。 测定 不应性是否与免疫或非免疫相关 因素（例如，败血症、发热等）可以通过对以下问题的答复加以澄清： HLA匹配的血小板输注。 两个区域血液中心都保持着 一个广泛的名单HLA型捐助者，并应能够获得一个 及时输注足够数量的HLA匹配血小板。 同种免疫的实验室评估将通过测定来确定 对于补体固定和非补体固定抗体， I类HLA决定簇和血小板上表达的其他同种抗原。 血小板上表达的非HLA同种异体抗原是一个重要的研究领域， 威斯康星州东南部血液中心。 血液 中心愿意提供同种抗体的参考检测 如有要求，对这些决定因素作出反应。 同种免疫是一种 这是治疗ANLL患者的临床医生的一个棘手问题。 拟议 研究应解决现有的问题， 预防或减少其发生的方法。

This proposal is submitted in response to RFA NIH 88-HL-12B to serve as a Clinical Center in a study designed to determine practical methods for reducing the incidence of alloimmunization and refractoriness to platelet transfusions in multitransfused patients with acute nonlymphocytic leukemia (ANLL). Transfusion therapies under consideration include use of: platelet concentrates from random, single donors prepared by apheresis techniques; leukocyte-poor platelet concentrates; and platelet concentrate exposed to ultraviolet irradiation. The incidence of alloimmunization in patients assigned to various protocols will be determined and will be compared with that of a "control" group treated with standardly prepared platelet concentrate. The study will be prospective, randomized, and single-blinded. Patients will be assigned to specific study arms on the basis of demographic information including history of pregnancy, etc. by the Coordinating Center. Patients with a new diagnosis of ANLL who undergo induction therapy at selected hospitals in Milwaukee and at the University of Wisconsin Hospitals in Madison will be eligible for the study. Platelet transfusions will be prescribed for therapeutic or prophylactic indications and will be prepared by The Blood Center of Southeastern Wisconsin and the American REd Cross Blood Services-Badger Region. Alloimmunization and refractoriness to platelet transfusions will be determined by clinical and laboratory parameters. Determination of whether refractoriness is related to immunologic or non-immunologic factors (e.g., sepsis, fever, etc.) may be clarified by the response to HLA-matched platelet transfusions. Both regional blood centers maintain an extensive list of HLA-typed donors and should be able to obtain an adequate number o HLA-matched platelet transfusions on a timely basis. Laboratory assessment of alloimmunization will be determined by assays for complement-fixing and non-complement-fixing antibodies reactive with class I HLA determinants and other alloantigens expressed on platelets. Non-HLA alloantigens expressed on platelets are a major research interest of The Blood Center of Southeastern Wisconsin. The Blood Center would be willing to provide reference testing for allo-antibodies reactive with such determinants if requested. Alloimmunization is a vexing problem for clinicians treating patients with ANLL. The proposed study should resolve existing questions about the effectiveness of methods for preventing or reducing its occurrence.