Blood vs. bone marrow stem transplant

血液与骨髓干移植

• 批准号: 6558550
• 负责人: Benjamin Djulbegovic
• 金额: $ 14.5万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6558550
• 关键词: blood /lymphatic neoplasm; bone marrow transplantation; clinical research; data collection; graft versus host disease; health science research analysis /evaluation; hematopoietic tissue transplantation; homologous transplantation; human data; human therapy evaluation; mathematical model; meta analysis; outcomes research; prognosis; stem cell transplantation; transplant rejection

DESCRIPTION (provided by applicant): Peripheral blood stem cells (PBSC) are used increasingly as an alternative to bone marrow (BM) as a source of stem cells for allogeneic (allo) transplantation in the management of hematologic malignancies. This shift in practice was based on the results of several small randomized controlled trials (RCTs), which indicated possible survival and disease-free survival advantages of PBSC over BM transplant (T). However, some trials showed that the use of PBSC is linked to higher levels of graft versus host disease, which in turn can compromise the survival of patients who received PBSC. Since these small trials could not individually achieve conclusive results about the relative effects of PBSC vs. BM transplant, substantial controversy about a possible advantage of PBSCT over BMT on mortality and disease free survival exists. This is a classic situation when the techniques of the systematic review (SR), aimed at assembling the totality of the evidence on the relative benefit and risks of the use of allogeneic PBSCT or BMT, should be used to solve this controversy and existing disagreement. Indeed, we recently performed such a systematic review with a meta-analytic (MA) quantitative summary to show that in comparison with allo-BMT, allo-PBSCT leads to better overall survival, less transplant related deaths, fewer relapses and prolonged disease free survival. We like to note here that by combining existing data sets, using a technique of SR/MA, we were able to demonstrate what none of the individual study was able to do: PBSCT is superior to BMT for the most of clinical outcomes. However, our study was based on the data extracted from the published studies. This is known to be an inferior type of SR/MA and may not provide definitive evidence. The gold-standard method to combine the totality of existing evidence is to perform individual patient data meta-analysis (IPD MA). Thus, by collecting individual patient data (from the existing data sets), we will be able to focus on the following objectives: 1. Is allo-PBSCT superior to allo-BMT in the management of hematological malignancies for a number of clinical end-points, including overall mortality, transplant-related mortality, relapse rates, disease-free survival, incidence of acute and chronic graft-versus-host disease (GVHD), incidence of chronic. Since some retrospective studies suggest that PBSCT may be more effective in hematological malignancies with a poor risk, while BMT may be more beneficial for the patients with good risk malignancies, we will test the following hypothesis: 2. Is there a subgroup of patients for whom BMT is superior to PBSCT? The technique of IPD MA is an ideal method to perform a subgroup analysis. Finally, since the main expected differences in outcomes might be the result of a different composition of allo-graft, we will test an additional hypothesis: 3. Is there a relationship between the composition of the graft (e.g. number of CD3 cells, number of CD34 cells) and the probability of development of acute and chronic GVHD? 4. Is there an effect of the GVHD prophylaxis regimen on the development of acute or chronic GVHD? Using IPD from studies that utilized different prophylaxis regimens it may be possible to test the interaction of GVHD prophylaxis among these studies. We will test all these hypotheses by collecting individual-patient data on each outcomes of interest from the existing data sets (i.e. from published and unpublished randomized studies) using the techniques of SR/MA.

描述（由申请人提供）： 外周血干细胞（PBSC）越来越多地用作骨髓（BM）的替代品，作为异基因（allo）移植治疗血液恶性肿瘤的干细胞来源。实践中的这种转变是基于几项小型随机对照试验（RCT）的结果，这些试验表明PBSC相对于BM移植（T）可能具有生存和无病生存优势。 然而，一些试验表明，PBSC的使用与更高水平的移植物抗宿主病有关，这反过来又会损害接受PBSC的患者的生存。由于这些小型试验无法单独获得关于PBSC与BM移植的相对效果的结论性结果，因此关于PBSCT相对于BMT在死亡率和无病生存率方面的可能优势存在实质性争议。 这是一种典型的情况，系统综述（SR）的技术旨在收集关于使用同种异体PBSCT或BMT的相对获益和风险的全部证据，应用于解决这一争议和现有分歧。事实上，我们最近进行了这样一个系统的审查与荟萃分析（MA）的定量总结，以表明与异基因骨髓移植相比，异基因PBSCT导致更好的总生存期，移植相关死亡较少，复发较少，无病生存期延长。我们在这里要注意的是，通过结合现有的数据集，使用SR/MA技术，我们能够证明没有一项单独的研究能够做到：PBSCT在大多数临床结局方面上级BMT。然而，我们的研究是基于从已发表的研究中提取的数据。 已知这是一种较低类型的SR/MA，可能无法提供明确的证据。 联合收割机整合现有证据的金标准方法是进行个体患者数据荟萃分析（IPD MA）。因此，通过收集个体患者数据（从现有数据集），我们将能够专注于以下目标：1.异基因外周血干细胞移植在治疗血液系统恶性肿瘤方面是否上级异基因骨髓移植，包括总死亡率、移植相关死亡率、复发率、无病生存率、急性和慢性移植物抗宿主病（GVHD）的发生率、慢性移植物抗宿主病（GVHD）的发生率。 由于一些回顾性研究表明，PBSCT可能是更有效的血液系统恶性肿瘤与低风险，而骨髓移植可能是更有益的患者与良好的风险恶性肿瘤，我们将测试以下假设：2。是否存在BMT上级PBSCT的患者亚组？IPD MA技术是进行亚组分析的理想方法。 最后，由于主要的预期结果差异可能是同种异体移植物成分不同的结果，我们将检验另一个假设：3。移植物的组成（例如CD 3细胞数量、CD 34细胞数量）与急性和慢性GVHD发生的可能性之间是否存在关系？4. GVHD预防方案对急性或慢性GVHD的发生是否有影响？使用来自使用不同预防方案的研究的IPD，可能测试这些研究中GVHD预防的相互作用。 我们将通过使用SR/MA技术从现有数据集（即来自已发表和未发表的随机研究）收集每个关注结局的个体患者数据来检验所有这些假设。