LONG TERM FOLLOW UP AND CHRONIC GRAFT VERSUS HOST DISEASE STUDIES

长期随访和慢性移植物与宿主疾病研究

• 批准号: 6300145
• 负责人: KEITH M SULLIVAN
• 金额: $ 32.64万
• 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: 2000-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6300145
• 关键词: FK506; bone marrow transplantation; cataract; chemoprevention; clinical research; cyclosporines; eye agent; graft versus host disease; homologous transplantation; hormone therapy; human subject; human therapy evaluation; immunoglobulins; immunotherapy; longitudinal human study; medical complication; mycophenolic acid; outcomes research; pathologic bone resorption; prednisone; psoralens; quality of life; sirolimus; skeletal disorder chemotherapy; thalidomide

The goal of this project is to improve means to prevent and treat chronic graft-versus-host disease (GVHD) which is the major determinant of late nonrelapse mortality following allogeneic stem cell transplantation. Currently 1,029 individuals survive 5 to 25 years after allogeneic transplantation at this Center. Among a cohort of 443 patients with chronic myelogenous leukemia in chronic phase transplanted since 1987 from HLA-identical sibling (n=251) or mismatched/unrelated (n=192) donors, late complications included: chronic GVHD (n=257), bacteremia (n=142 episodes), cataracts (n=119), lung disease (n=59), bone disease (n=50), and secondary neoplasms (n=10). Multivariate analysis confirmed a highly significant association of all infections developing after day 120 with chronic GVHD. Use of alternative donor marrow and use of corticosteroids before onset of chronic GVHD were also significant independent covariates. Accordingly, we propose four interrelated specific aims to improve morbidity-free survival: 1) Provide comprehensive follow-up to identify evolving late effects of transplant regimens; 2) Evaluate means to prevent chronic GVHD and steroid toxicity by prolonging the duration of cyclosporine (CSP) prophylaxis or by use of a novel regimen of CSP/rapamycin immunosuppression; 3) Improve treatment of chronic GVHD by selecting thalidomide, FK506, rapamycin, or mycophenolate mofetil from pilot studies for study in Phase III trials; 4) Evaluate new diagnostic and interventive methods to reduce other causes of posttransplant morbidity (e.g. cataract formation and bone disease) and determine in a placebo- controlled study of immunoglobulin prophylaxis whether infections and mortality can be reduced after unrelated donor transplantation. This project is the clinical hub providing continuous monitoring of a large number of transplant recipients for real time investigation of abnormalities of hematopoietic function, graft rejection and GVHD. Although long-term survival has improved in recent years, clinical study of chronic GVHD and late events is vital for further improvement in patient outcome.

该项目的目标是改进预防和治疗慢性病的手段 移植物抗宿主病（GVHD）是晚期的主要决定因素 同种异体干细胞移植后的非复发死亡率。 目前有 1,029 名个体在异体移植后存活 5 至 25 年 在这个中心进行移植。 在 443 名患者的队列中 自1987年起移植的慢性粒细胞白血病慢性期 HLA 相同的兄弟姐妹 (n=251) 或不匹配/不相关 (n=192) 捐赠者，晚期 并发症包括：慢性 GVHD（n=257）、菌血症（n=142）、 白内障 (n=119)、肺部疾病 (n=59)、骨病 (n=50) 和继发性 肿瘤（n=10）。 多变量分析证实了高度显着 第 120 天后发生的所有感染与慢性 GVHD 的关联。 使用替代供体骨髓并在发病前使用皮质类固醇 慢性 GVHD 也是显着的独立协变量。 因此， 我们提出了四个相互关联的具体目标来提高无发病率 生存：1) 提供全面的随访以识别晚期进化 移植方案的影响； 2) 评估预防慢性GVHD的方法 通过延长环孢素 (CSP) 的持续时间来减轻类固醇毒性 预防或使用 CSP/雷帕霉素新方案 免疫抑制； 3）通过选择改善慢性GVHD的治疗 初步研究中的沙利度胺、FK506、雷帕霉素或吗替麦考酚酯 用于 III 期试验研究； 4) 评估新的诊断和 减少移植后发病率的其他原因的干预方法 （例如白内障形成和骨病）并在安慰剂中确定- 免疫球蛋白预防的对照研究是否感染和 非亲缘供体移植后死亡率可以降低。 这 项目是一个临床中心，提供对大型患者的持续监测 实时调查移植受者数量 造血功能异常、移植物排斥反应和GVHD。 尽管近年来长期生存率有所改善，但临床研究 慢性 GVHD 和晚期事件的发生对于进一步改善 患者的结果。