Unrelated allogeneic bone marrow-derived mesenchymal stem cells for steroid-refractory acute graft-versus-host disease: a phase I/II study

• DOI: 10.1007/s12185-013-1399-4
• Publication Date: 2013-07-16T05:04:36Z
• Authors: Kazuo Muroi; Koichi Miyamura; Kazuteru Ohashi; Makoto Murata; Tetsuya Eto; Naoki Kobayashi; Shuichi Taniguchi; Masahiro Imamura; Kiyoshi Ando; Shunichi Kato; Takehiko Mori; Takanori Teshima; Masaki Mori; Keiya Ozawa
• Keywords: Adult; Male; 0301 basic medicine; Graft vs Host Disease; Bone Marrow Cells; Middle Aged; Allografts; Mesenchymal Stem Cell Transplantation; Disease-Free Survival; 3. Good health; Survival Rate; 03 medical and health sciences; Child, Preschool; Hematologic Neoplasms; Humans; Female; Unrelated Donors

We conducted a multicenter phase I/II study using mesenchymal stem cells (MSCs) manufactured from the bone marrow of healthy unrelated volunteers to treat steroid-refractory acute graft-versus-host disease (aGVHD). Fourteen patients with hematological malignancies who suffered from grade II (9 patients) or III aGVHD (5) were treated. Affected organs were gut (10 patients), skin (9 patients), and liver (3 patients). Seven patients had two involved organs. The median age was 52. No other second-line agents were given. MSCs were given at a dose of 2 × 10(6) cells/kg for each infusion twice a week for 4 weeks. If needed, patients were continuously given MSCs weekly for an additional 4 weeks. By week 4, 13 of 14 patients (92.9 %) had responded to MSC therapy with a complete response (CR; n = 8) or partial response (PR; n = 5). At 24 weeks, 11 patients (10 with CR and 1 with PR) were alive. At 96 weeks, 8 patients were alive in CR. A total of 6 patients died, attributable to the following: underlying disease relapse (2 patients), breast cancer relapse (1), veno-occlusive disease (1), ischemic cholangiopathy (1), and pneumonia (1). No clear adverse effects associated with MSC infusion were observed. Third party-derived bone marrow MSCs may be safe and effective for patients with steroid-refractory aGVHD.