Transfusion Medicine/Hemostasis Clinical Research

描述(由申请人提供)： 这笔赠款的重点是血液疾病的随机临床试验，这需要在NHLBI输血医学/止血临床研究网络中采用多中心方法。三家哈佛教学医院组成了一个联盟，申请这个核心临床中心。这些机构之间的关键联系已经到位，包括输血医学联合计划和波士顿血友病中心。成人和儿科血液学和输血医学服务，以及与我们机构的高危产科服务的合作。第一项拟议的研究以儿科为重点，时间框架为两年。这项随机II期试验的目的是评估利妥昔单抗(抗CD20单抗)与硫唑嘌呤对患有严重或缓解性慢性特发性血小板减少性紫癜的儿童和青少年的疗效。主要疗效结果将是研究第90天的血小板计数。次要结果包括出血评分趋势，一年内的血小板计数，药物的副作用，以及在两个疗程中是否需要‘抢救’方案。我们提议的长期研究将集中在血栓性血小板减少性紫癜(TTP)的随机治疗策略上。目的是确定与标准的血浆置换/强的松治疗相比，在强的松和血浆置换的基础上加用利妥昔单抗治疗是否有助于缓解诱导。主要疗效结果包括确诊后30天内接受血浆置换治疗不超过9次的患者(早期应答者)和24个月后存活且无复发的患者的比例。次级终点将包括死亡率、30天后缓解的患者比例、每个治疗组的首次缓解时间、每个患者的血浆置换手术次数、每个组的复发次数、缓解时间和复发率，在每组中，按是否存在VWV金属蛋白酶抑制剂和VW蛋白酶活性的量化进行分层。第三，我们建议一个多中心联盟进行一项III期随机研究，比较两种不同剂量的静脉注射丙种球蛋白方案在妊娠期间有新生儿同种免疫性血小板减少的风险。建议为每个输血网络研究中的患者的血清、血浆和DNA建立一个储存库，以促进进一步的生物学研究。

DESCRIPTION (provided by applicant): The focus of this grant is randomized clinical trials for hematologic disorders, which require a multi-center approach in the NHLBI Transfusion Medicine/Hemostasis Clinical Research Network. Three Harvard teaching hospitals form a consortium for this Core Clinical Center application. Key linkages among the institutions are in place, including the Joint Program in Transfusion Medicine, and the Boston Hemophilia Center. Adult and pediatric hematology and transfusion medicine services are represented, as well as collaboration with the high-risk obstetrics services at our institutions. The first proposed study has a pediatric focus and two-year time frame. The aim of this randomized phase II trial is to assess the efficacy of rituximab (anti-CD20 monoclonal antibody) vs. azathioprine, in children and adolescents with severe or refractor chronic idiopathic thrombocytopenic purpura. The primary efficacy outcome will be platelet counts at study day 90. Secondary outcomes include bleeding score trend, platelet counts at one year, side effects of medication, and requirement for 'salvage' regimens during either course of therapy. Our proposed long-term study will focus on randomized treatment strategies in thrombotic thrombocytopenic purpura (TTP). The aim is to determine whether rituximab therapy in addition to prednisone and plasmapheresis will facilitate remission induction, compared to standard therapy of plasmapheresis/ prednisone alone. Primary efficacy outcomes include the fraction of patients alive with no more than 9 plasma exchange procedures at 30 days from diagnosis (early responders) and the fraction of patients alive and relapse-free at 24 months. Secondary endpoints will include the death rate, the fraction of patients in remission at 30 days, the time to first remission in each treatment group, the number of plasma exchange procedures per patients, the number of relapses per group, and the time to remission and relapse rate, in each group, stratified for the presence of absence of VWV metalloprotease inhibitors and quantification of VW protease activity. Third, we propose a multicenter consortium for a phase III randomized study comparing two different dosage regimens of intravenous gamma globulin during pregnancies at risk for neonatal alloimmune thrombocytopenia. A repository for sera, plasma, and DNA from patients in each of the transfusion network studies is proposed, to facilitate further biological studies.