Novel Therapies in Hemostasis and Transfusion Medicine

描述(由申请人提供)： 本申请是对题为《输血医学/止血临床网络》的RFA HL-02-001的响应，是纽约长老会医院-威尔康奈尔医学院-哥伦比亚内科医学院的联合体。它为纽约市20%的大都会地区提供医疗保健，并在2小时内为2000万人提供医疗服务。它是参与止血和输血医学临床研究的医生和科学家的混合体，具有儿科、内科、病理学和外科的专业知识。该组织既有患者群体，也有参与网络中其他中心提出的临床试验所需的临床专业知识。具体目的1是难治性ITP的临床试验，定义为脾切除术无效的儿童和成人ITP。旨在通过比较两种新的治疗方法来关注难治性ITP的病理生理学。一种是利妥昔单抗，它是一种抗CD20，可以耗尽B细胞的接受者，应该是一种有效的免疫抑制剂，可以治疗像ITP这样的“纯”自身抗体疾病。有描述其有效性的初步数据，这应该会优化其使用。另一组打算使用血小板生成素或类似物(TPO)通过刺激血小板生成来增加血小板数量。这个ARM假设难治性ITP的一个关键因素是血小板生成减少，这可以通过TPO刺激来纠正。脾切除登记将包括在内，以方便登记符合条件的患者。特定目标2旨在优化输血的粒细胞。这将对长期严重的中性粒细胞减少患者有很大的潜在好处，他们遭受相当大的发病率和偶尔因感染而死亡。此外，长期住院的费用也很高。过去，对粒细胞输注的研究表明，输注粒细胞几乎没有什么好处，而且有很大的毒性。目前的研究将探索不同的粒细胞制备方法，以及评估其疗效的新技术。具体目标3表明，该联盟能够参与各种止血和输血药物疾病的治疗方案。该联盟包括纽约血液中心的Grima博士，他每年为大约20名TTP患者进行治疗；领先的康奈尔中心，用于管理同种免疫性血小板减少症患者；以及一个大型血友病中心。

DESCRIPTION (provided by applicant): This application is in response to RFA HL-02-001 entitled Transfusion Medicine/Hemostasis Clinical Network and is a consortium of the New York Presbyterian Hospital - Weill Cornell College of Medicine-Columbia College of Physicians and Surgeons. It provides health care to > 20% of the New York City metropolitan area and has access to > 20 million people within 2 hours. It is an amalgam of physicians and scientists involved in clinical research in Hemostasis and Transfusion Medicine with expertise in Pediatrics, Internal Medicine, Pathology, and Surgery. The group has both the patient population and the clinical expertise required to participate in clinical trials proposed by other centers in the Network. Specific Aim 1 is a clinical trial of refractory ITP, defined as children and adults with ITP who have failed to respond to splenectomy. It intends to focus on the pathophysiology of refractory ITP by comparing two novel treatments. One, rituximab, is an anti-CD20 which depletes the recipient of B cells and should be an effective immunosuppressant in a "pure" autoantibody disease like ITP. There is preliminary data describing its effectiveness which should optimize its use. The other arm intends to use thrombopoietin or mimetic (TPO) to increase the platelet count by stimulating platelet production. This arm hypothesizes that a critical element in refractory ITP is a decreased production of platelets which can be rectified by stimulation with TPO. A registry of splenectomy will be included to facilitate enrollment of eligible patients. Specific Aim 2 intends to optimize granulocytes for transfusion. This would be of great potential benefit to patients with prolonged, severe neutropenia who suffer considerable morbidity and occasional mortality from infection. There is also the high cost of prolonged hospitalizations. In the past, studies of granulocyte transfusion showed little benefit and significant toxicity. The current study will explore different methods of preparation of granulocytes and also novel techniques for evaluation of their efficacy. Specific Aim 3 demonstrates that the consortium is able to participate in protocols for a wide variety of disorders of hemostasis and transfusion medicine. The consortium includes Dr. Grima of the NY Blood Center who annually phereses approximately 20 TTP patients; a leading center, Cornell, for management of patients with alloimmune thrombocytopenia;and a large hemophilia center.