Blood vs. bone marrow stem transplant

University Of South Florida, Tampa FL

Investigators

Linked publications & trials

Abstract

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.