Determinants of Relapse Risk After BMT for ALL

ALL BMT 后复发风险的决定因素

基本信息

  • 批准号:
    8089570
  • 负责人:
  • 金额:
    $ 29.37万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2007
  • 资助国家:
    美国
  • 起止时间:
    2007-07-01 至 2014-04-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Hematopoietic stem cell transplantation (HSCT) is used as the major salvage strategy for patients with relapsed or refractory acute lymphoblastic leukemia (ALL), providing long-term disease control for some patients. Unfortunately, the majority of patients fail and relapse remains the most frequent cause of failure. The studies proposed here will utilize specimens obtained from patients enrolled on Children's Oncology Group ASCT0431. ASCT0431 is a nationwide randomized phase III study comparing two regimens (standard vs. sirolimus-based) designed to control graft vs. host disease (GVHD), and testing the hypothesis that the mTOR inhibitor sirolimus will control ALL at a point of minimal residual disease and thus decrease relapse risk and improve survival. Mechanisms of post-HSCT relapse fall into two broad categories: 1) the failure of anti-leukemic therapy to control disease; and 2) the ability of MRD to escape allogeneic immunosurveillance (the GVL effect). We hypothesize that sirolimus will improve the outcome of allogeneic HSCT for ALL by eliminating or suppressing residual ALL during the period post-HSCT when GVL may be absent due to immature immune reconstitution, thus providing adequate GVHD control without decreasing the GVL effect. A method to improve HSCT outcome in this fashion would be a major advance in transplantation and antileukemia therapy. These focused and integrated biological studies will assess the relative importance of sirolimus antileukemic effect and GVL directly in children treated for relapsed ALL with defined HSCT therapies and GVHD prophylaxis, and for whom blast samples from the initial relapse are available, in the critical setting of a Phase III trial. We will accomplish two Specific Aims: 1) Assess the impact of sirolimus on patient PBMC and on the ALL blasts. 2) Assess the impact of sirolimus-based GVHD prophylaxis on the GVL effect. The work is directly relevant to the mission of the agency because it seeks to improve transplant outcome, study the mechanisms of action of this agent in the context of a phase III study, and improve cure rates for patients with relapsed ALL. Lay Summary. We have very good treatments for the most common childhood leukemia, called ALL. However, if the disease comes back (relapse), most of the children will not survive. This research will look how a new drug used in bone marrow transplant, called sirolimus, may help prevent relapse in patients and study in the cells how it may act to prevent this problem.
描述(由申请人提供):造血干细胞移植(HSCT)作为复发或难治性急性淋巴细胞白血病(ALL)患者的主要抢救策略,为部分患者提供了长期的疾病控制。不幸的是,大多数患者都失败了,复发仍然是最常见的失败原因。这里提出的研究将利用从儿童肿瘤组ASCT0431登记的患者中获得的标本。ASCT0431是一项全国性的随机III期研究,比较两种方案(标准方案和基于西罗莫司的方案),旨在控制移植物抗宿主病(GVHD),并验证mTOR抑制剂西罗莫司将在最小残留疾病点控制ALL,从而降低复发风险并提高生存率的假设。造血干细胞移植后复发的机制可分为两大类:1)抗白血病治疗未能控制疾病;2) MRD逃避同种异体免疫监视(GVL效应)的能力。我们假设西罗莫司将通过消除或抑制残留的ALL来改善同种异体造血干细胞移植治疗ALL的结果,在造血干细胞移植后,GVL可能因不成熟的免疫重建而缺失,从而在不降低GVL效果的情况下提供足够的GVHD控制。以这种方式改善造血干细胞移植结果的方法将是移植和抗白血病治疗的重大进展。这些集中和综合的生物学研究将评估西罗莫司抗白血病效果和GVL直接在接受明确的HSCT治疗和GVHD预防的复发性ALL儿童中的相对重要性,并且在III期试验的关键环境中,对于初始复发的blast样本是可用的。我们将完成两个具体目标:1)评估西罗莫司对患者PBMC和ALL细胞的影响。2)评估以西罗莫司为基础的GVHD预防对GVL效果的影响。这项工作与该机构的使命直接相关,因为它寻求改善移植结果,在III期研究中研究该药物的作用机制,并提高复发性ALL患者的治愈率。总结。我们对最常见的儿童白血病(ALL)有很好的治疗方法。然而,如果疾病复发(复发),大多数儿童将无法生存。这项研究将研究一种用于骨髓移植的新药西罗莫司如何帮助防止患者复发,并在细胞中研究它如何预防这一问题。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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STEPHAN A. GRUPP其他文献

STEPHAN A. GRUPP的其他文献

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{{ truncateString('STEPHAN A. GRUPP', 18)}}的其他基金

The cell and gene therapy toolkit for junior faculty
初级教师的细胞和基因治疗工具包
  • 批准号:
    9903575
  • 财政年份:
    2020
  • 资助金额:
    $ 29.37万
  • 项目类别:
The cell and gene therapy toolkit for junior faculty
初级教师的细胞和基因治疗工具包
  • 批准号:
    10380059
  • 财政年份:
    2020
  • 资助金额:
    $ 29.37万
  • 项目类别:
Determinants of Relapse Risk After BMT for ALL
ALL BMT 后复发风险的决定因素
  • 批准号:
    7618461
  • 财政年份:
    2007
  • 资助金额:
    $ 29.37万
  • 项目类别:
Determinants of Relapse Risk After BMT for ALL
ALL BMT 后复发风险的决定因素
  • 批准号:
    7406724
  • 财政年份:
    2007
  • 资助金额:
    $ 29.37万
  • 项目类别:
Determinants of Relapse Risk After BMT for ALL
ALL BMT 后复发风险的决定因素
  • 批准号:
    7260150
  • 财政年份:
    2007
  • 资助金额:
    $ 29.37万
  • 项目类别:
Determinants of Relapse Risk After BMT for ALL
ALL BMT 后复发风险的决定因素
  • 批准号:
    7843565
  • 财政年份:
    2007
  • 资助金额:
    $ 29.37万
  • 项目类别:
USE OF mTOR INHIBITORS IN B CELL LEUKEMIA
mTOR 抑制剂在 B 细胞白血病中的应用
  • 批准号:
    7424976
  • 财政年份:
    2005
  • 资助金额:
    $ 29.37万
  • 项目类别:
USE OF mTOR INHIBITORS IN B CELL LEUKEMIA
mTOR 抑制剂在 B 细胞白血病中的应用
  • 批准号:
    6920407
  • 财政年份:
    2005
  • 资助金额:
    $ 29.37万
  • 项目类别:
USE OF mTOR INHIBITORS IN B CELL LEUKEMIA
mTOR 抑制剂在 B 细胞白血病中的应用
  • 批准号:
    7230434
  • 财政年份:
    2005
  • 资助金额:
    $ 29.37万
  • 项目类别:
USE OF mTOR INHIBITORS IN B CELL LEUKEMIA
mTOR 抑制剂在 B 细胞白血病中的应用
  • 批准号:
    7617848
  • 财政年份:
    2005
  • 资助金额:
    $ 29.37万
  • 项目类别:

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