Is peripheral blood or bone marrow a better source of stem cells for transplantation in cases of HLA-matched unrelated donors? A meta-analysis
Introduction
Hematopoietic stem cell transplantation is a standard therapeutic approach for the cure of hematological malignant and non-malignant diseases. Originally, bone marrow (BM) was the only source of stem cells for transplantation, but as newer transplant protocols were developed, peripheral blood (PB) came into clinical use as a source of stem cells, which are mobilized by granulocyte colony stimulating factor. Peripheral blood is currently the predominant source of stem cells of which was used more than bone marrow according to the CIBMTR [1], [2]. It is more convenient to harvest peripheral blood, which is thought to contain more CD34+ cells and immunocompetent T cells. This is supposed to lead to faster engraftment and immune reconstitution and better disease control by an enhanced graft-versus-leukemia (GVL) effect, which simultaneously increases the risk of graft-versus-host disease (GVHD) and transplant-related mortality (TRM) [3]. Bone marrow has been reported to correlate with fewer cases of GVHD and TRM, as well as with improved survival; conversely, stem cells from the bone marrow are correlated with an increased risk of relapse. However, patients who received stem cells from BM donors experienced more toxicity, pain and a slower recovery after transplantation [4].
Many clinical trials have compared peripheral blood and bone marrow as sources of stem cells on the outcomes of transplantation. Peripheral blood stem cell transplantation (PBSCT) has been reported to be associated with more acute or chronic GVHD but with a better disease-free survival (DFS), especially in cases of advanced disease [5], [6]. Almost all of the related studies have found a faster engraftment in patients who received stem cells from the PB. A study of matched sibling donors showed that PBSCT is associated with a higher risk of acute and chronic GVHD accompanied by an improved DFS and a lower rate of relapse. However, the transplant-related mortality was similar between patients in the PB and BM groups [7]. Another study showed that PBSCT was associated with faster engraftment, an increased incidence of grades 3–4 acute GVHD and extensive chronic GVHD; PBSCT was associated with a decreased relapse in both early and late disease. Improved disease-free survival was observed in late disease, but the overall survival (OS) was similar because of an increased severity of acute GVHD (grades 3–4) and an increase in TRM [8].
Conclusions from the sibling donor transplantations were mostly consistent, but data from unrelated donors were limited. The only randomized controlled study, using matched and mismatched unrelated donors, reported that an increase in 2-year chronic GVHD and less graft failure were associated with PBSCT and that no survival advantages were found [9]. Bertz conducted a trial in patients with acute myeloid leukemia (AML) and myelo-dysplastic syndrome (MDS). After a median follow-up of 118 months, the DFS rate was significantly higher after PBSCT without increased GVHD, especially in late diseases; the OS rate was improved, and the incidence of TRM also decreased [10]. Conclusions are also controversial in HLA-matched or mismatched unrelated donor stem cell transplantations [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23]. We conducted this meta-analysis in HLA-matched unrelated donors, and therefore our objective was to evaluate the prognostic effectiveness of peripheral-blood and bone marrow as sources of stem cells in hematopoietic stem cell transplantation that involves HLA-matched unrelated donors.
Section snippets
Search strategy and selection criteria
We performed systematic literature searches in PubMed and Medline, with the key words “peripheral blood and bone marrow and transplantation” through April, 2014. The inclusion criteria included whether randomized studies that compared the transplantation outcomes of PB versus BM used a human leukocyte antigen (HLA) matched unrelated donor and whether data on the engraftment, OS, DFS, acute/chronic-GVHD, relapse and TRM were available. Reviews were excluded from this study as were all articles
Search results
We obtained 17,538 initial hits from PubMed and Medline, using the key words “peripheral blood and bone marrow and transplantation”. A total of 2340 studies published as review papers were excluded. Out of the remaining 15,198 studies, 15,169 were excluded because they didn’t meet the criteria of “compare the outcome of PBSCT versus BMT” and involved an “unrelated donor”. A total of 29 studies remained, out of which only 15 met the criterion of “HLA matched unrelated donor”. Four of the 15
Discussion
The results of our meta-analysis suggest that PBSCT was associated with the following: better neutrophil and platelets engraftment; and a probably lower risk for relapse, an increased risk for acute GVHD and TRM with the RIC regimen for only one study was included. No significant influences on chronic GVHD and survival were observed. These results were consistent with those of Remberger [11] and Eapen [26], who used both HLA-matched and mismatched unrelated donors [11], [26].
As is known, the
Conflict of interest statement
The authors indicated no potential conflicts of interest.
Authors’ contributions
Xi Zhang and Sha Wu designed the systematic review. Sha Wu and Cheng Zhang performed the literature search and extracted the data from eligible studies. Sha Wu contributed to the structuring of the tables and figures. Analysis of data and interpretation was done by Sha Wu, Cheng Zhang, Xi Zhang, Ya-qi Xu and Tian-xia Deng. The manuscript was written by Sha Wu, and Xi Zhang was responsible for the critical revisions of the manuscript. All authors read and approved the final manuscript.
Acknowledgement
This study was funded by grants from the National Natural Science Foundation of China (No. 81070388).
Sha Wu is a postgraduate student of medicine (Department of Hematology, Xinqiao Hospital, Third Military Medical University). She was interests in the field of hematopoietic stem cell transplantation. She has focused on the main factors to intervene so as to reduce transplant-related mortality and increase survival and engaged in the clinical work on the corresponding field since 2012.
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Sha Wu is a postgraduate student of medicine (Department of Hematology, Xinqiao Hospital, Third Military Medical University). She was interests in the field of hematopoietic stem cell transplantation. She has focused on the main factors to intervene so as to reduce transplant-related mortality and increase survival and engaged in the clinical work on the corresponding field since 2012.
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Co-first authors.