Mesenchymal Stem Cells for Treatment of Severe Acute and Extensive Chronic Graft-Versus-Host Disease.

Mesenchymal stem cells (MSC) from adult bone marrow have the capacity to differentiate to several mesenchymal tissues and inhibit T-cell alloreactivity in vitro. We have used MSC to treat grades III-IV acute graft-versus-host disease (GVHD) in 14 patients and extensive chronic GVHD in two patients. The MSC dose was median 1.0 (range 0.4–9) x 10E6 cells/kg body weight of the recipient. No side-effects were seen after MSC infusions. Nine patients received one dose, six patients received two doses and one patient received three doses. MSC donors were in two cases HLA-identical sibling donors, twelve haploidentical donors and ten third-party HLA-mismatched donors. Among the 14 patients treated for severe acute GVHD, six had complete responses, four showed improvement and one had stable disease. Three were not evaluable: two due to early death and one due to short follow-up. MSC donor DNA was detected in lymph node and colon in one of the patients who died. Among the 14 patients treated for severe acute GVHD, nine are alive between two months up to three years after transplantation. Four of these patients have extensive chronic GVHD. One patient transplanted for AML in relapse has recurrent leukaemia. The two patients treated for extensive chronic GVHD had transient responses. One of them died of Epstein-Barr virus lymphoma. We conclude that MSC have immune-modulatory and tissue repairing effects and therefore may be used for treatment of severe GVHD.