Favorable response to human adipose tissue-derived mesenchymal stem cells in steroid-refractory acute graft-versus-host disease.

There is no consistently effective therapy for patients with steroid-refractory acute graft-versus-host disease (GVHD). Various alternative approaches have been tested, including antithymocyte globulin, mycophenolate mofetil (MMF), pentostatin, and monoclonal antibodies; however, they have only been modestly successful. The purpose of our study was to evaluate the efficacy of human adipose-tissue-derived mesenchymal stem cells (AMSC) as salvage therapy for steroid-refractory acute GVHD. Six patients with steroid-refractory grades III-IV acute GVHD received IV infusions of AMSC. The AMSC dose was 1.0x10(6)/kg. No side effects were noted after the AMSC infusions. Five patients were treated once and one patient twice. Two patients received AMSC from haplo-identical family donors and four from unrelated mismatched donors. Acute GVHD disappeared completely in five of six patients, four of whom are alive after a median follow-up of 40 months (range, 18-90 months) after the initiation of AMSC therapy. All four surviving patients are in good clinical condition and in remission of their hematological malignancy. Two patients died-one with no obvious response to AMSC died of multiorgan failure and one a relapse of leukemia. These results suggested that AMSC is a promising treatment for severe steroid-resistant acute GVHD.