Key messages
• Blood stem cell transplantation is a relevant therapeutic option to treat people with blood disorders. Blood stem cells can be taken from different sources, including peripheral blood and bone marrow.
• Bone marrow transplantation and peripheral blood stem cell transplantation probably lead to similar results in terms of overall survival.
• For this update, we found no new eligible studies. Future research should aim to find out which is the best stem cell source for adults with blood disorders. More information is needed about options such as haploidentical family donors, where the donor is half a match to the recipient, as this is an emerging treatment option.
What is stem cell transplantation?
Stem cells are special cells that can develop into different cell types and repair damaged tissues. Stem cell transplantation is an important treatment option for people with blood cancers, bone marrow failure, or birth defects in blood formation. In stem cell transplantation, stem cells are taken from the blood, bone marrow, or (rarely) umbilical cord blood of a healthy donor and given to the recipient. The aim is to replenish the recipient's body with healthy cells after pretreatment with chemotherapy, radiation, or both. The classical stem cell transplantation technique introduced in the 1970s involves extracting bone marrow stem cells from the donor's pelvic bone. Since the early 1990s, it has been possible to collect stem cells from the peripheral blood by stimulating the donor with a specific hormone called G-CSF (granulocyte colony-stimulating factor). This procedure is easier, leads to faster recovery of blood cells after transplantation, and has largely replaced bone marrow transplantation in adults with blood cancers.
Bone marrow versus peripheral blood
For successful transplantations, it is better if the stem cells come from a healthy donor with genetically compatible tissue. The donor can be related or unrelated to the recipient. Both stem cell sources have advantages and disadvantages. Some studies have found that complications such as graft-versus-host disease (GvHD) are less common after bone marrow stem cell transplantation. GvHD occurs when the donor cells attack the recipient's healthy tissue. However, the growth of stem cells and new blood cells (known as engraftment) is slower after bone marrow transplantation than after peripheral blood transplantation. Another important result is disease-free survival (the time until the disease returns or the recipient dies). Most studies have found that disease-free and overall survival are similar with both types of stem cell transplantation.
What did we want to find out?
We wanted to know if bone marrow transplantation is better than peripheral stem cell transplantation for improving:
• overall survival;
• disease-free survival;
• death without the disease returning;
• GvHD that persists over the long term;
• Severe GvHD that occurs in the short term; and
• Quality of life.
What did we do?
We searched for studies that compared bone marrow transplantation with peripheral blood cell transplantation in adults with blood disorders. We compared and summarised the results of the studies and rated our confidence in the evidence based on factors such as study methods and sizes.
What did we find?
In the previous version of this review (from 2014), we found nine studies involving 1521 people with blood disorders. They were conducted in Canada, the USA, New Zealand, Brazil, Australia, Egypt, and across Europe. The average age of the people with blood disorders was between 21 and 45 years across all the studies. In this update, we found no new studies, but we did find new information on quality of life and infections from one of the previously included studies.
Main results
This updated review does not affect the conclusions of our previous review.
Bone marrow transplantation compared with peripheral blood stem cell transplantation likely results in little to no difference in overall survival, and may result in little or no difference in disease-free survival and death without the disease returning. Bone marrow transplantation compared with peripheral blood stem cell transplantation likely reduces the risk of long-term GvHD and may reduce the risk of severe short-term GvHD. People who undergo bone marrow transplantation may have a better quality of life after five years.
What are the limitations of the evidence?
We are only moderately confident in our results on overall survival, long-term GvHD, and severe short-term GvHD. We have little confidence in the evidence for disease-free survival, death without the disease returning, and quality of life. The main limitation is that the people measuring the results in the studies knew which type of transplantation each person received, and this may have affected their judgement.
How up to date is this evidence?
This is an update of our previous review (2014). We included evidence up to November 2022.
Moderate-certainty evidence suggests little to no difference in overall survival following allo-HSCT using bone marrow versus peripheral blood stem cells (the current clinical standard stem cell source). Low-certainty evidence suggests little to no difference between the stem cell sources in terms of disease-free survival and non-relapse or transplant-related survival. BMT likely reduces the risk of extensive chronic GvHD and overall chronic GvHD compared with PBSCT. Evidence from two RCTs suggests that BMT compared with PBSCT may result in higher long-term quality of life, possibly due to the lower chronic GvHD incidence.
With this update, we aimed to supply the most recent data on the choice of stem cell source for allo-HSCT in adults by including new evidence published up to November 2022. We identified no new ongoing studies and no new RCTs with published results. Further research in this field is warranted.
Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is an established treatment option for many malignant and non-malignant haematological disorders. Peripheral blood stem cells represent the main stem cell source in malignant diseases due to faster engraftment and practicability issues compared with bone marrow stem cells.
Since the early 2000s, there have been many developments in the clinical field. Allo-HSCT using haploidentical family donors (haplo-HSCT) has emerged as an alternative for people who do not have human leukocyte antigen (HLA)-matched siblings or unrelated donors. In addition, the introduction of new methods and strategies in allo-HSCT, such as the use of post-transplant cyclophosphamide (PT-Cy), better donor selection, the more frequent administration of anti-thymocyte globulins (ATGs), but also improved management of side effects such as graft-versus-host disease (GvHD) and infection, have impacted outcomes after allo-HSCT.
In addition, as transplant indications and strategies continue to adapt in line with novel research findings, the effect of the stem cell source on post-transplant outcomes is unclear. For our analysis, we considered peripheral blood stem cells as the standard graft source for adults with haematological malignancies.
This is an update of a review first published in 2014.
To assess the effect of bone marrow transplantation versus peripheral blood stem cell transplantation in adults with haematological malignancies with regard to overall survival, disease-free survival, incidence of non-relapse or transplant-related mortality, incidence of extensive chronic graft-versus-host disease (GvHD), incidence of acute GvHD grades III to IV, incidence of overall chronic GvHD, and quality of life.
For this update we searched CENTRAL, MEDLINE, Embase, and two trials registries on 2 November 2022 with no language restrictions.
We included randomised controlled trials (RCTs) comparing bone marrow transplantation (BMT) with peripheral blood stem cell transplantation (PBSCT) in adults (aged ≥ 18 years) with haematological malignancies.
Two review authors independently selected studies and extracted data. We evaluated risk of bias using the original Cochrane risk of bias tool (RoB 1), and we evaluated the certainty of the evidence using the GRADE approach.
The updated search identified no new studies for inclusion. We found two additional reports relating to a previously included study; they provided new data on quality of life and infection rates after transplantation. As these are clinically relevant outcomes, quality of life was added to the summary of findings table (replacing acute GvHD II to IV), and rate of infection was added to our list of secondary outcomes.
We included nine RCTs with a total of 1521 participants. Overall, the risk of bias in the included studies was low. Median participant age across studies ranged from 21 to 45 years, and studies took place in Canada, the USA, New Zealand, Brazil, Australia, Egypt, and across Europe.
Bone marrow transplantation (BMT) compared with peripheral blood stem cell transplantation (PBSCT) likely results in little to no difference in overall survival (hazard ratio (HR) for all-cause death 1.07, 95% CI 0.91 to 1.25; 6 studies, 1330 participants; moderate-certainty evidence).
There may be little to no difference between BMT and PBSCT in terms of disease-free survival (HR for disease recurrence or all-cause death 1.04, 95% CI 0.89 to 1.21; 6 studies, 1225 participants; low-certainty evidence) and non-relapse or transplant-related mortality (HR 0.98, 95% CI 0.76 to 1.28; 3 studies, 758 participants; low-certainty evidence).
BMT compared with PBSCT likely results in lower rates of extensive chronic GvHD (HR 0.69, 95% CI 0.54 to 0.90; 4 studies, 765 participants; moderate-certainty evidence) and overall chronic GvHD (HR 0.72, 95% CI 0.61 to 0.85; 4 studies, 1121 participants; moderate-certainty evidence). BMT compared with PBSCT may reduce the incidence of acute GvHD grades III to IV, although the 95% CI of the HR is also compatible with no effect (HR 0.75, 95% CI 0.55 to 1.02; 3 studies, 925 participants; moderate-certainty evidence).
Evidence from two trials that used different quality of life assessment instruments suggests that BMT compared with PBSCT may be associated with higher quality of life five years after transplantation.