Autologous hematopoietic stem cell transplantation in refractory rheumatoid arthritis - Sustained response in two of four patients

Objective. To investigate the safety and efficacy of immune ablation with s ubsequent autologous hematopoietic stem cell transplantation (HSCT) in seve re rheumatoid arthritis (RA), Methods, Four patients with refractory RA and poor prognostic indicators we re treated. Stem cells were collected and lymphocytes were depleted by 2.3- 4.0 logs, The conditioning regimen included cyclophosphamide (200 mg/kg), a ntithymocyte globulin (90 mg/kg), and, for 1 patient, total body irradiatio n (TBI) with 400 cGy, Improvement was evaluated according to the American C ollege of Rheumatology (ACR) preliminary definition of improvement in RA (A CR 20), and also according to the ACR 50 and ACR 70 criteria. Results. HSCT was well tolerated. Three patients fulfilled the ACR 70 crite ria at 1 month and 3 months post-HSCT, One patient did not fulfill the ACR 20 criteria because of persistent joint tenderness, despite improvement of the joint swelling. At 6 months post-HSCT, 1 patient fulfilled the ACR 70 c riteria and 1 fulfilled the ACR 50 criteria, and these 2 patients fulfilled the ACR 70 criteria at 9 months post-HSCT, The other 2 patients (including the patient who received TBI) did not meet the ACR 20 criteria at 6 months and 9 months post-HSCT, The only patient with followup of >9 months fulfil led the ACR 70 criteria at 20 months post-HSCT. Conclusion. In this series, autologous HSCT was safe and effective in induc ing major clinical response and maintained significant benefit for 2 patien ts at 9 months and 20 months posttreatment, respectively, Sustained respons e did not occur for 2 of 4 patients. A regimen dose-response effect may exi st, but the addition of TBI did not prevent disease relapse for 1 of the pa tients. More aggressive T cell depletion of the autograft, use of a myeloab lative regimen, or use of an allograft may be necessary to decrease relapse rates.