A pilot trial for severe, refractory systemic autoimmune disease with stem cell transplantation.
OBJECTIVE
To evaluate the feasibility, efficacy, and safety of high dose immunosuppressive therapy (HDIT) and autologous hemopoietic stem cell transplantation (HSCT) with CD34+ cell selection in patients with severe, refractory autoimmune diseases.


METHODS
Twenty-six patients with persistent systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), or systemic sclerosis (SSc) who had been treated unsuccessfully with conventional treatment were enrolled in the trial in Peking Union Medical College Hospital from September 1999 to June 2004. The patients received HDIT with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected. Disease activity, adverse effect, hemopoietic and immune reconstitution, and time to recurrence of disease were monitored.


RESULTS
Overall treatment related mortality was 7.7% (2/26) with 1 patient died of cytomegalovirus infection and another of severe pneumonia. Relapse occurred in 3 SLE patients (17.6%) in 37, 26, and 19 months posttransplantation respectively, and 1 RA patient in 15 months posttransplantation. SLE Disease Activity Index (SLEDAI) scores of SLE survivors decreased significantly (P < 0.01). RA patients recorded a drop of Disease Activity Score 28 (DAS 28). The pSS patient remained symptoms free up to now, more than 50 months after the transplantation.


CONCLUSIONS
HSCT can be performed relative safely in patients with severe autoimmune disease. Short-term effect of HSCT is promising. However treatment related mortality and relapse were observed in a subset of patients.
Leng
Xiao-Mei
XM
Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730.
Zhao
Yan
Y
Zhou
Dao-Bing
DB
Situ
Huifen
H
Li
Tai-Sheng
TS
Shen
Ti
T
Zhao
Yong-Qiang
YQ
Zeng
Xiao-Feng
XF
Zhang
Feng-Chun
FC
Dong
Yi
Y
Tang
Fu-Lin
FL
D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy; D008297:Male; D010865:Pilot Projects; D012008:Recurrence; D012859:Sjogren's Syndrome / Q000276:immunology / Q000628:therapy; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous
D018952:Antigens, CD34; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide