PHASE I/II TRIAL OF RITUXIMAB FOR CHRONIC, SEVERE ITP IN CHILDREN AND ADOLES

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。儿童期免疫性血小板减少症（ITP）最常见的是一种自限性疾病，约70%的受影响儿童在一年内消退。在少数患者中，病情会变成慢性。尽管许多慢性ITP患者具有良性病程，需要很少或不需要持续治疗，但这些个体中的一小部分具有持续的严重疾病。在严重受累的患者中，一线药物（类固醇、抗D球蛋白、IVIG或脾切除术）的无效性是一个令人烦恼的临床问题。这些患者出血的风险相对较高，并且没有可用的文献表明许多可用的干预措施中的任何一种比任何其他干预措施（包括根本不干预）更安全或更有效。从长远来看，回答这类问题的最佳方法是通过随机临床试验。我们建议这项试点研究作为这样一个随机试验的序幕。利妥昔单抗是一种有吸引力的选择，在严重的ITP。在大多数情况下，该疾病的病理生理学被认为是抗体介导的血小板破坏，并且对于严重受累患者的初始试验，毒性特征是合理的。据报告，这些反应是持久的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Immune thrombocytopenia (ITP) in childhood is most commonly a sef-limited disorder, resolving within a year in about 70% of affected children. In a minority of patients, the condition becomes chronic. Whereas many patients with chronic ITP have benign courses, requiring little or no ongoing therapy, a fraction of these individuals has persistent severe disease. Refractoriness to first line agents (steriods, anti-D globulin, IVIG or splenectomy) in severly affected patients is a vexing clinical problem. These patients are at relatively high risk for blieeding, and no available literature suggests that any of the many available interventions is safer or more effective than any other ( including no intervention at all). In the long run, the best way to answer this type of question is by randomized clinical trial. We propose this pilot study as prologue to such a randomized trial. Rituximab is an attractive choice in severe ITP. The pathophysiology of the disorder is thought to be anitbody mediated platelet destruction in the majority of cases, and the toxicity profile is reasonable for initial trials in severly affected patients. Durable responses have been reported.