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: 6101871
• 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: 1999
• 资助国家: 美国
• 起止时间: 1999-04-07 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6101871
• 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.

该项目的目的是提高预防和治疗慢性的手段 移植物与宿主病（GVHD）是最近的主要决定因素 同种异体干细胞移植后的非恢复死亡率。 目前有1,029个人在同种异体后5到25年幸存 在这个中心移植。 在443例患者中 自1987年以来从慢性期移植的慢性骨髓白血病 HLA认同的兄弟姐妹（n = 251）或不匹配/无关（n = 192）供体，迟到 并发症包括：慢性GVHD（n = 257），菌血症（n = 142个情节）， 白内障（n = 119），肺病（n = 59），骨病（n = 50）和次级 肿瘤（n = 10）。 多变量分析证实了非常重要的 第120天与慢性GVHD发生的所有感染的关联。 在开始之前，使用替代供体骨髓和使用皮质类固醇 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特定目标，以提高无发病率 生存：1）提供全面的后续行动，以确定迟到 移植方案的影响； 2）评估预防慢性GVHD的手段 和类固醇毒性通过延长环孢霉素的持续时间（CSP） 预防或通过使用新型CSP/雷帕霉素方案 免疫抑制； 3）通过选择来改善慢性GVHD的治疗 从试点研究 进行第三阶段试验的研究； 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 预防免疫球蛋白的对照研究是否感染和 无关供体移植后可以降低死亡率。 这 项目是临床中心，可连续监测大型 进行实时调查的移植接收者数量 造血功能，移植排斥和GVHD的异常。 尽管近年来长期生存有所提高，但临床研究 慢性GVHD和后期事件对于进一步的进一步改善至关重要 病人的结果。