CHRONIC GRAFT VS HOST DISEASE AND LONG TERM FOLLOW-UP PROGRAM

慢性移植物与宿主疾病及长期随访计划

• 批准号: 6338864
• 负责人: KEITH M SULLIVAN
• 金额: $ 17.57万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6338864
• 关键词: FK506; aplastic anemia; artificial immunosuppression; bone disorder; cataract; clinical research; drug adverse effect; graft versus host disease; hematopoietic tissue transplantation; homologous transplantation; human subject; human therapy evaluation; iatrogenic disease; immunoglobulins; immunosuppressive; longitudinal human study; lung disorder; quality of life; sirolimus; thalidomide; ultraviolet therapy

The objective of this project is to reduce the late morbidity and mortality of hematopoietic stem cell transplantation. The major determinants of these late complications include treatment-related toxicities, immunodeficiency and chronic graft-versus-host disease (GVHD). To date, 385 stem cell recipients have been followed annually for up to 25 years after transplantation for aplastic anemia and allied hematologic diseases. Among this cohort (including 105 patients currently more than 10 years posttransplant), late complications included: chronic GVHD (n=179), lung disease (n=67), cataracts (n=47), depression (n=46), bone disease (n=35), lithiasis (n=26), secondary neoplasms (n=10), and major or moderate infections (n-1626 episodes). Accordingly, we propose four interrelated specific aims; 1) Monitor late events and complications after stem cell transplantation and determine the dynamics of psychosocial recovery. In addition, patients will participate in studies of the mechanisms of posttransplant lung disease, pediatric growth and development, and secondary malignancies following transplantation; 2) Reduce infections and mortality after unrelated transplantation in a placebo controlled trial of immunoglobulin prophylaxis. Other studies will evaluate new diagnostic and interventive methods to reduce the morbidity of posttransplant cataract and bone disease; 3) Prevent development of chronic GVHD by novel approaches to long-term immunosuppression and early adjunctive therapy of acute GVHD with ultraviolet radiation; 4) Improve treatment of chronic GVHD by evaluating the efficacy of FK-506, thalidomide, rapamycin and mycophenolate mofetil in an integrated series of pilot and Phase III clinical trials. Concern for the late effects of stem cell transplantation is especially important as new disease indications, preparative regimens and stem cell sources are explored. Although overall survival has improved in recent years, investigation of the late morbidity of transplantation is vital for the well-being of the stem cell recipient.

该项目的目标是降低晚期发病率和死亡率 造血干细胞移植。 主要决定因素 这些晚期并发症包括与治疗相关的毒性， 免疫缺陷和慢性移植物抗宿主病（GVHD）。 迄今为止， 每年对 385 名干细胞接受者进行长达 25 年的追踪 再生障碍性贫血和相关血液系统疾病移植后。 在该队列中（包括 105 名目前病龄超过 10 年的患者） 移植后），晚期并发症包括：慢性 GVHD（n=179）、肺 疾病 (n=67)、白内障 (n=47)、抑郁症 (n=46)、骨病 (n=35)、 结石病 (n=26)、继发性肿瘤 (n=10) 以及重度或中度 感染（n-1626 次）。 因此，我们提出四个相互关联的 具体目标； 1) 监测干细胞治疗后的晚期事件和并发症 移植并确定心理社会恢复的动态。 在 此外，患者将参与机制研究 移植后肺部疾病、儿科生长和发育，以及 移植后继发性恶性肿瘤； 2) 减少感染和 安慰剂对照试验中无关移植后的死亡率 免疫球蛋白预防。 其他研究将评估新的诊断和 减少移植后白内障发病率的干预方法 骨病； 3) 通过新方法预防慢性 GVHD 的发展 长期免疫抑制和急性 GVHD 的早期辅助治疗 有紫外线照射； 4) 改善慢性 GVHD 的治疗 评估 FK-506、沙利度胺、雷帕霉素和霉酚酸酯的疗效 mofetil 正在进行一系列综合试验和 III 期临床试验。 人们尤其担心干细胞移植的后期影响 与新的疾病适应症、准备方案和干细胞一样重要 来源进行了探索。 尽管近年来总体生存率有所改善 多年来，对移植晚期发病率的调查对于 干细胞接受者的健康。