Severe Chronic Neutropenia International Registry

严重慢性中性粒细胞减少症国际登记处

• 批准号: 6908901
• 负责人: DAVID Chandler DALE
• 金额: $ 42.78万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6908901
• 关键词: DNA; RNA; blood; bone marrow; chronic disease /disorder; clinical research; congenital blood disorder; disease /disorder etiology; dyserythropoietic anemia; family genetics; genetic disorder; genetic registry /resource /referral center; human subject; information dissemination; international cooperation; interview; leukemia; medical outreach /case finding; neutropenia; pathologic process; patient /disease registry; questionnaires; sample collection; serum; tissue resource /registry

DESCRIPTION (provided by applicant): The Severe Chronic Neutropenia International Registry (the Registry) opened in 1994 to study the long-term safety and efficacy of granulocyte-colony stimulating factor (G-CSF) treatment for patients with congenital, cyclic, and idiopathic neutropenia. The Registry initially evaluated hematological parameters, growth and development, consequence of pregnancy, and other important clinical events. Through the Registry we have learned that patients with congenital neutropenia on long-term G-CSF have a risk of evolution to leukemia of approximately two percent per year. Then, through development of a repository of biological materials, linkage analysis, DNA sequencing, and cellular studies, we have learned that both cyclic and most cases of congenital neutropenia are attributable to mutations in the gene encoding neutrophil elastase. We have also learned that mutations in the receptor for G-CSF frequently occur in the course of evolution of congenital neutropenia to acute myelogenous leukemia. We have also collaborated with other research groups studying candidate genes as causes for neutropenia. The Registry currently includes more than 1300 patients and the Repository contains more than 650 samples from patients, normal relatives, and normal volunteers. The Registry is now an international research organization based at the University of Washington. In this application, we request funding to continue the work of the Registry. The specific aims are: (1) To continue to enroll and follow patients through carefully longitudinal studies, emphasizing increasing diversity of racial, age, and ethnic backgrounds; (2) To expand a bank of biological materials, to support genetic and molecular research, and to study the evolution of patients to myelodysplasia and leukemia and; (3) To enhance our efforts to disseminate information on the causes, consequences, and treatments of diseases causing severe chronic neutropenia. All of these efforts are directed toward improving understanding in the care of patients with severe neutropenia.

描述（由申请人提供）：严重慢性中性粒细胞减少症国际登记研究（登记研究）于1994年开始，旨在研究粒细胞集落刺激因子（G-CSF）治疗先天性、周期性和特发性中性粒细胞减少症患者的长期安全性和有效性。登记研究最初评价了血液学参数、生长发育、妊娠后果和其他重要临床事件。通过登记研究，我们了解到，先天性中性粒细胞减少症患者长期使用G-CSF，每年有大约2%的风险演变为白血病。然后，通过开发生物材料库、连锁分析、DNA测序和细胞研究，我们了解到周期性和大多数先天性中性粒细胞减少症都可归因于中性粒细胞弹性蛋白酶编码基因的突变。我们还了解到G-CSF受体的突变经常发生在先天性中性粒细胞减少症向急性髓细胞性白血病的演变过程中。我们还与其他研究小组合作，研究中性粒细胞减少症的候选基因。该登记处目前包括1300多名患者，储存库包含来自患者、正常亲属和正常志愿者的650多个样本。 书记官处现在是一个设在华盛顿大学的国际研究组织。在本申请中，我们要求提供资金，以继续书记官处的工作。具体目标是：（1）通过仔细的纵向研究继续招募和随访患者，强调种族、年龄和民族背景的日益多样性;（2）扩大生物材料库，支持遗传和分子研究，并研究患者向骨髓增生异常和白血病的演变;（3）加强传播关于导致严重慢性中性粒细胞减少症的疾病的原因、后果和治疗方法的信息。所有这些努力都是为了提高对严重中性粒细胞减少症患者护理的理解。