Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Allogeneic Mesenchymal Stem Cells Transplantation in Severe and Refractory Systemic Lupus Erythematosus.
Sun1, Lingyun, Wang1, Dandan, Zhang1, Huayong, Liang1, Jun, Feng1, Xuebing, Hou2, Yayi
To assess the long-term efficacy and safety of allogenic bone marrow (BM) or umbilical cord (UC) mesenchymal stem cells transplantation (MSCT) for patients with severe and refractory systemic lupus erythematosus (SLE).
A single-arm trial involved 82 SLE patients, aged from 12 to 56 years old, average disease duration was 44 months. 24 patients were infused once with BM MSC, 50 patients received once UC MSC, while the other 8 patients received both MSC twicely. Allogeneic MSC were administered >=1.0×106/body weight(KG)intravenously. BM MSC were aspirated from related healthy donors and expanded in vitro, and UC MSC were obtained from Stem Cell Center of Jiangsu Province of China. The clinical manifestations and laboratory parameters were compared pre- and post-MSCT, with a mean follow-up of 16.5 months (range, 3 to 36 months). Side effects were monitored all the time during and post-MSCT.
Complete remission (CR) of disease activity (SLEDAI less than 3 and prednisone dose<=10mg/d) was seen in 9/41 (22%) patients 1 year post-MSCT and up to 9/16 (56%) and 3/5 (60%) at 2 and 3 years point respectively. Probability of disease relapse (DR) or unresponsive to MSCT (SLEDAI increased >=3 and an increase in prednisone or immunosuppressive drug) was 8/41 (20%) at 1 year and 4/16 (25%) at 2 years visit. Of 5 patients completed 3 years visit, 2 of which with DR, and both were unresponsive to a second MSCT. The other 6 patients, who received second MSCT, reached to complete or partial remission. Significant improvements in SLEDAI score were examined 3 months (9.4±0.5) post-MSCT (n=82, p<0.01 vs pre-MSCT 14.0±0.6), and further decline in 1 and 2 years visit (4.9±0.4 vs 14.1±0.6, n=41 in 1 year, 3.6±0.6 vs 18.4±1.5, n=16 in 2 years, p<0.01). SLEDAI score <3 in 3 patients at 3 years visit. Amelioration of lupus nephritis was identified by the obvious decline of 24-hour proteinuria in 3 (1771±157mg vs 2799±152mg, n=64, p<0.05) and 6 months (1353±153mg vs 2584±179mg, n=31, p<0.05) visit, with further decline at 1 year visit (945±177mg vs 2045±112mg, n=20, p<0.05), and for 11 patients completed 2 years visit (989±289mg, p<0.05). Serology index showed serum albumin and complement C3 increased combined with decline of serum autoimmune antibodies. In addition, of 22 patients with moderate to severe hematological disorders, haematoglobin and/or platelet count reached to almost normal levels post-MSCT. Furthermore, 4 patients had central nervous system involvement (seizures, cerebralgia) with improvement and no relapsed post-MSCT. Significant improvements of glomerular filtration rate were found for 3 patients 12, 12, 20 months after MSCT respectively (from 65.23, 71.86, 23.45 ml/min to 94.45, 100.07, 69.82 ml/min). There was no difference in efficacy between BM and UC MSCT. Four patients died 5, 6, 6, 10 months post-MSCT respectively, due to uncontrolled infection or disease relapse. No transplant related mortality or any significant toxicity was observed and overall 3 years survival rate was 95% (78/82).
Allogeneic MSCT is safe and results in amelioration of disease activity. These data provide a foundation for conducting BM or UC MSCT for severe and treatment-refractory SLE.
To cite this abstract, please use the following information:
Sun, Lingyun, Wang, Dandan, Zhang, Huayong, Liang, Jun, Feng, Xuebing, Hou, Yayi; Allogeneic Mesenchymal Stem Cells Transplantation in Severe and Refractory Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1143