Mesenchymal stromal cells as treatment or prophylaxis for acute or chronic graft‐versus‐host disease in haematopoietic stem cell transplant (HSCT) recipients with a haematological condition

Background Recipients of allogeneic haematopoietic stem cell transplants (HSCT) can develop acute or chronic, or both forms of graft‐versus‐host disease (a/cGvHD), whereby immune cells of the donor attack host tissues. Steroids are the primary treatment, but patients with severe, refractory disease have limited options and a poor prognosis. Mesenchymal stromal cells (MSCs) exhibit immunosuppressive properties and are being tested in clinical trials for their safety and efficacy in treating many immune‐mediated disorders. GvHD is one of the first areas in which MSCs were clinically applied, and it is important that the accumulating evidence is systematically reviewed to assess whether their use is favoured. Objectives To determine the evidence for the safety and efficacy of MSCs for treating immune‐mediated inflammation post‐transplantation of haematopoietic stem cells. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library 2018, Issue 12), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), Web of Science: Conference Proceedings Citation Index‐Science (CPCI‐S) (from 1990) and ongoing trial databases to 6 December 2018. No constraints were placed on language or publication status. Selection criteria We included RCTs of participants with a haematological condition who have undergone an HSCT as treatment for their condition and were randomised to MSCs (intervention arm) or no MSCs (comparator arm), to prevent or treat GvHD. We also included RCTs which compared different doses of MSCs or MSCs of different sources (e.g. bone marrow versus cord). We included MSCs co‐transplanted with haematopoietic stem cells as well as MSCs administered post‐transplantation of haematopoietic stem cells. Data collection and analysis We used standard methodological procedures expected by Cochrane. We employed a random‐effects model for all analyses due to expected clinical heterogeneity arising from differences in participant characteristics and interventions. Main results We identified 12 completed RCTs (879 participants), and 13 ongoing trials (1532 enrolled participants planned). Of 12 completed trials, 10 compared MSCs versus no MSCs and two compared different doses of MSCs. One trial was in people with thalassaemia major, the remaining trials were for haematological malignancies. Seven trials administered MSCs to prevent GvHD, whereas five trials gave MSCs to treat GvHD.