Blood vs. bone marrow stem transplant

描述(由申请人提供)： 外周血干细胞(PBSC)越来越多地被用作骨髓(BM)的替代品，作为异基因(Allo)移植的干细胞来源，用于治疗恶性血液病。实践中的这一转变是基于几个小型随机对照试验(RCT)的结果，这些试验表明，与骨髓移植(T)相比，PBSC可能具有生存和无病生存优势。然而，一些试验表明，使用PBSC与更高水平的移植物抗宿主疾病有关，这反过来可能会危及接受PBSC的患者的生存。由于这些小规模试验不能单独得出PBSC与骨髓移植的相对效果的决定性结果，因此PBSCT在死亡率和无病存活率方面可能比BMT更有优势的争议很大。这是一种经典的情况，当旨在收集关于使用异基因PBSCT或BMT的相对益处和风险的全部证据的系统审查(SR)技术应该被用来解决这一争议和现有的分歧时。事实上，我们最近用荟萃分析(MA)定量总结进行了这样的系统性综述，以表明与allo-BMT相比，allo-PBSCT可以导致更好的总体生存，更少的移植相关死亡，更少的复发和更长的无病生存期。在这里，我们想指出的是，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研究能够做到的：在大多数临床结果方面，PBSCT优于BMT。然而，我们的研究是基于从已发表的研究中提取的数据。已知这是一种劣质类型的SR/MA，可能无法提供确凿的证据。结合所有现有证据的金标准方法是进行个别患者数据荟萃分析(IPD MA)。因此，通过收集单个患者的数据(从现有的数据集)，我们将能够专注于以下目标：1.在许多临床终点，allo-PBSCT在治疗血液系统恶性肿瘤方面是否优于allo-BMT，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可能对风险较低的血液系统恶性肿瘤更有效，而BMT可能对风险较高的恶性疾病患者更有利，我们将检验以下假设：2.是否存在BMT优于PBSCT的患者亚组？IPD-MA技术是进行亚群分析的理想方法。最后，由于主要预期结果的差异可能是由于同种异体移植物的不同成分造成的，我们将检验另一个假设：3.移植物的组成(如CD3细胞数量、CD34细胞数量)与急性和慢性GVHD的发生概率之间是否存在关系？4.GVHD预防方案对急性或慢性GVHD的发展是否有影响？利用采用不同预防方案的研究中的IPD，有可能在这些研究中测试GVHD预防措施的相互作用。我们将通过使用SR/MA技术从现有数据集中(即，从已发表和未发表的随机研究中)收集感兴趣的每个结果的个体患者数据来检验所有这些假设。

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.