부산대학교 도서관

Objective: To investigate the safety and efficacy of immunoablation and subsequent autologous hematopoietic stem cell transplantation (HSCT) in refractory rheumatoid arthritis (RA). Methods: Three patients with severe, refractory RA were treated. We mobilized autologous hematopoietic stem cells (HSCs) with cyclophosphamide (Cy) and granulocyte colony-stimulating factor. HSCs were collected and enriched ex vivo using CD34-positive immunoselection. Two different immunoablative conditioning regimens were employed; fludarabine-Cy-anti-thymoayte glonulin (ATG) in patients whose disease activity was transiently ameliorated in response to Cy used in stem cell mobilization, or fludarabine-busulfan-ATG in those who didn`t show any response to that. Results: Median time to engraftment with an absolute neutrophil count greater than 500/μl and nontransfused platelet count greater than 20,000/μl was 15 days (range 12-16) and 9 days (range 7-13), respectively. Regimen-related toxicity was minimal. Two patients were markedly improved at 2 or 3 months after HSCT, repectively. In another patient, disease activity was transiently subsided, but relapsed at 2 months after HSCT, which led to reinstitution of anti-rheumatic medications. This resulted in subsequent marked improvement of disease activity whereas her disease had been refractory to these medications. Conclusions: These results underscore the feasibility and potential efficacy of intensive immunosuppression followed by autologous HSCT for treatment of refractory rheumatoid arthritis. The durability of remission remains to be clarified.