Cotransplantation of Mesenchymal Stem Cells Might Prevent Death from Graft-versus-host Disease (GVHD) Without Abrogating Graft-versus-tumor Effects After HLA-mismatched Allogeneic Transplantation Following Nonmyeloablative Conditioning

Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD) after myeloablative allogeneic HCT. This prompted us to investigate in a pilot study whether MSC infusion before HCT could allow nonmyeloablative (NMA) HCT (a transplant strategy based nearly exclusively on graft-versus-tumor effects for tumor eradication) from HLA-mismatched donors to be performed safely. Twenty patients with hematologic malignancies were given MSCs from third party unrelated donors 30-120 minutes before peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors, after conditioning with 2 Gy total body irradiation (TBI) and fludarabine. The primary endpoint was safety, defined as a 100-day incidence of nonrelapse mortality (NRM) <35%. One patient had primary graft rejection, whereas the remaining 19 patients had sustained engraftment. The 100-day cumulative incidence of grade II-IV acute GVHD (aGVHD) was 35%, whereas 65% of the patients experienced moderate/severe chronic GVHD (cGVHD). One-year NRM (10%), relapse (30%), overall survival (OS) (80%) and progression-free survival (PFS) (60%), and 1-year incidence of death from GVHD or infection with GVHD (10%) were encouraging. These figures compare favorably with those observed in a historic group of 16 patients given HLA-mismatched PBSCs (but no MSCs) after NMA conditioning, which had a 1-year incidence of NRM of 37% (P = .02), a 1-year incidence of relapse of 25% (NS), a 1-year OS and PFS of 44% (P = .02), and 38% (P = .1), respectively, and a 1-year rate of death from GVHD or infection with GVHD of 31% (P = .04). In conclusion, our data suggest that HLA-mismatched NMA HCT with MSC coinfusion appeared to be safe.