Weak evidence suggests that prophylactic use of mesenchymal stem cells (MSCs) may reduce the risk of chronic graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), according to a recent Cochrane review.
However, other uses of MSCs with HSCT – such as prophylaxis with MSCs for acute GVHD or treatment of GVHD – lack evidence of efficacy, reported lead author Sheila A. Fisher, PhD, of National Health Service Blood and Transplant in Oxford (England), and her colleagues.
The investigators noted that most studies included in the review had low-quality evidence.
“[R]andomization methods were poorly reported and several of the included studies were subject to a high risk of performance bias and reporting bias,” the investigators wrote in the Cochrane Database of Systematic Reviews. “One trial which started in 2008 has not been published and the progress of this trial is unknown, leading to potential publication bias. The quality of evidence was therefore low or very low for all outcomes due to a high risk of bias as well as imprecision due to the low number of overall participants, and in some cases, evidence based on a single study.”
The investigators identified 25 randomized, controlled trials (RCTs) involving MSCs for GVHD, of which 12 were completed (879 participants) and 13 were ongoing (1,532 planned participants). Out of the 12 completed trials, 2 compared different doses of MSCs, while 10 compared MSCs with no MSCs. Five trials investigated treatment with MSCs and seven investigated prophylactic use.
The one finding that was supportive of MSCs, albeit based on low-quality evidence, showed that prophylactic use reduced the risk of chronic GVHD, compared with no prophylaxis (risk ratio, 0.66). Other findings were less supportive or unsupportive of MSCs.
Prophylactic use of MSCs had little or no impact on risk of acute GVHD (RR, 0.86; low-quality evidence), risk of relapse of malignant disease (RR, 1.08; low-quality evidence), or all-cause mortality (hazard ratio, 0.85; low-quality evidence).
Treatment with MSCs was disappointing across the board. Risk of all-cause mortality was unaffected (HR, 1.12; very low–quality evidence) and a minimal impact was found for complete responses in acute GVHD (RR, 1.16; very low–quality evidence).
Although treatment of chronic GVHD with MSCs was associated with an improved complete response rate (RR, 5.00), the investigators noted that this finding came from a single trial with 40 participants that was deemed to have very low–quality evidence. The two trials comparing doses of MSCs found no differences between treatment groups.
“Despite a number of reports of positive outcomes from the use of MSCs for treating acute GVHD, the evidence to date from RCTs has not supported the conclusion that they are an effective therapy,” the investigators wrote.
The study was funded by NHS Blood and Transplant. Dr. Fischer reported having no financial disclosures. One coauthor reported research funding from the Leukemia and Lymphoma Research charity and the National Institute for Health Research.
SOURCE: Fisher SA et al. Cochrane Database Syst Rev. 2019 Jan 30. doi: 10.1002/14651858.CD009768.pub2.