Optimizing Treatment for TTP and Platelet Refractoriness

优化 TTP 和血小板不应期的治疗

• 批准号: 7116761
• 负责人: JANICE G MC FARLAND
• 金额: $ 29.3万
• 依托单位: VERSITI WISCONSIN, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7116761
• 关键词: blood disorder chemotherapy; blood transfusion; blood treatment; clinical research; clinical trials; cooperative study; corticosteroids; hemostasis; histocompatibility; histocompatibility typing; human subject; human therapy evaluation; immunosuppressive; isoantibody; patient oriented research; platelet transfusion; relapse /recurrence; splenectomy; thrombocytopenic purpura; thrombosis; von Willebrand factor

DESCRIPTION (provided by applicant): Study I: Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of uncertain etiology that causes multi-organ dysfunction due to occlusion of small blood vessels by microthrombi. Over the past three decades plasma therapy has reduced the mortality rate from nearly 100% to about 20%. Although most patients recover from the initial episode, the relapse rate is high, and TTP remains a disease with substantial morbidity and mortality. Recent discovery of an association between decreased yon Willebrand factorcleaving protease (vWCP) levels and disease activity together with the demonstration of an autoantibody directed at this protein in some patients, raise the possibility that additional immunomodulatory therapy may be of benefit. We propose a randomized study comparing plasma exchange to plasma exchange plus corticosteroids to test the hypothesis that corticosteroids will increase the rate of durable complete responses. We also propose to determine if splenectomy will decrease the subsequent relapse rate in patients who have experienced a relapse of TTP. Studies correlating vWCP levels to disease activity and additional laboratory studies characterizing other possible disease correlates are planned. Study II: Prevention strategies for platelet alloimmunization and accompanying platelet transfusion refractoriness are not completely effective, particularly in individuals previously exposed to HLA and platelet antigens through transfusion of non-leukocyte reduced blood products or pregnancy. Selecting platelet products to avoid a refractory patient's alloantibody response is a mainstay of transfusion support for these patients but there is no consensus on which selection strategy is most effective for this clinical problem. We propose to compare the effectiveness of platelet crossmatching with HLA matching in providing platelet transfusion support to patients who are refractory to random donor platelet transfusions. In this context we will also determine the extent to which factors unrelated to HLA or platelet-specific alloimmunization (non-immune factors, ABO incompatibility) influence platelet transfusion responses. This information will be extremely useful in designing effective and cost-efficient platelet transfusion protocols for refractory patients.

描述（由申请人提供）： 研究I：血栓性血小板减少性紫癜（TTP）是一种罕见的不确定病因疾病，由于微杆菌对小血管遮挡，会引起多器官功能障碍。 在过去的三十年中，血浆疗法将死亡率从近100％降低到约20％。 尽管大多数患者从初始发作中恢复过来，但复发率很高，而TTP仍然是一种具有大量发病率和死亡率的疾病。 最近发现，YON WILLEBRAND因子分裂蛋白酶（VWCP）水平降低与疾病活动之间的关联，以及在某些患者中针对该蛋白质的自身抗体的证明，增加了可能有益的免疫调节治疗的可能性。 我们提出了一项随机研究，将血浆交换与等离子体交换以及皮质类固醇相比，以测试皮质类固醇会增加耐用的完整反应速率的假设。 我们还建议确定脾切除术是否会降低经历了TTP复发的患者的随后复发率。 计划将VWCP水平与疾病活动和其他可能疾病相关的实验室研究相关联。 研究II：预防血小板同种免疫性和随附血小板输血耐受性的策略并不完全有效，尤其是在以前通过非白细胞减少血液产物或妊娠的人以前暴露于HLA和血小板抗原的人。 选择血小板产品以避免难治性患者的同种抗体反应是对这些患者的输血支持的主要支持，但是尚无共识，哪种选择策略最有效。 我们建议将血小板交叉匹配与HLA匹配的有效性与为对随机供体血小板输血难治性的患者提供血小板输血支持。 在这种情况下，我们还将确定与HLA或血小板特异性同种免疫无关的因素（非免疫因子，ABO不兼容）会影响血小板输血反应。 该信息将在为难治性患者设计有效且具有成本效益的血小板输血方案方面非常有用。