Human adipose-derived stem cells for treatment of severe refractory acute graft-versus-host disease / 中国组织工程研究

ABSTRACT

BACKGROUND: There is no consistently effective therapy for patients with steroid-refractory acute graft-versus-host disease (GVHD). A variety of alternative approaches have been tested, including antithymocyte globulin, mycophenolate mofetil (MMF), pentostatin, and monoclonal antibodies; however, these treatments have been only modestly successful. OBJECTIVE: To further evaluate the efficacy of human adipose-derived stem cells (ASCs) as the salvage therapy for steroid-refractory acute GVHD. DESIGN: A clinical trial.SETTING: Department of Haematology, Henan Institute of Haematology, Henan Tumor Hospital.PARTICIPANTS: The clinical trial was performed at the Henan Institute of Haematology from September 2002 to August 2005. Eight patients were treated with ASCs for grades Ⅲ-Ⅳ steroid-resistant acute GVHD. The study was approved by the Ethics Committee at Henan Tumor Hospital and informed consent was obtained from patients and ASCs donors before they enrolled.METHODS: Eight patients with steroid-refractory grades Ⅲ-Ⅳ acute GVHD received intravenous infusions of ASCs. The ASCs dose was 1.0×106/kg. Seven patients were treated once and one patients twice. Four patients received ASCs from haplo-identical family donors and four from unrelated mismatched donors. MAIN OUTCOME MEASURES: The efficacy of human ASCs as the salvage therapy for steroid-refractory acute GVHD. RESULTS: No side effects were noted after the ASCs infusions. Acute GVHD disappeared completely in seven of eight patients and six of these seven patients are still alive after the median follow-up of 30 months (range 11-90 months) after the initiation of ASCs therapy. All four surviving patients were in good clinical condition and in remission of their hematological malignancy. Two patients died-one with no obvious response to ASCs died of multiorgan failure and one of relapse of leukemia. CONCLUSION: These results suggest that ASCs is a very promising treatment for severe steroid-resistant acute GVHD.