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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。儿童免疫性血小板减少症(ITP)最常见的是一种自限性疾病，大约70%的受影响儿童在一年内消失。在少数患者中，这种情况会变成慢性的。虽然许多慢性ITP患者的病程是良性的，几乎不需要持续治疗，但这些患者中有一小部分人患有持续性的严重疾病。严重感染的患者对一线药物(类固醇、抗D球蛋白、静脉注射免疫球蛋白或脾切除术)的耐受性是一个令人头疼的临床问题。这些患者出血的风险相对较高，而且没有可用的文献表明，许多可用的干预措施中有任何一种比任何其他干预措施更安全或更有效(包括根本不干预)。从长远来看，回答这类问题的最佳方式是随机临床试验。我们建议这项先导性研究作为这种随机试验的序幕。利妥昔单抗是治疗重症ITP的有吸引力的选择。在大多数情况下，这种疾病的病理生理学被认为是抗体介导的血小板破坏，在严重影响的患者的初步试验中，毒性分布是合理的。据报道，采取了持久的应对措施。

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.