Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study.
BACKGROUND
Patients with systemic lupus erythematosus (SLE) who experience persistent multiorgan dysfunction, despite standard doses of intravenous cyclophosphamide, represent a subset of patients at high risk of early death. We investigated the safety and efficacy of immune suppression and autologous haemopoietic stem-cell infusion to treat such patients.


METHODS
From 1996, we selected patients with persistent SLE despite use of cyclophosphamide. Patients underwent dose-intense immune suppression and autologous haemopoietic stem-cell (CD34) infusion. Peripheral blood lymphocytes were analysed by flow cytometry, ELISA, and T-cell-receptor spectratyping before and after transplantation. We mobilised autologous haemopoietic stem cells with 2.0 g/m2 cyclophosphamide and 10 microg/kg granulocyte colony stimulating factor daily, enriched with CD34-positive selection, and reinfused after immunosuppression with 200 mg/kg cyclophosphamide, 1 g methylprednisolone, and 90 mg/kg equine antithymocyte globulin.


RESULTS
Nine patients underwent stem-cell mobilisation but two were excluded before transplantation because of infection. The remaining seven received high-dose chemotherapy and stem-cell infusion. Median time to an absolute neutrophil count higher than 0.5x10(9)/L and nontransfused platelet count higher than 20x10(9)/L was 9 days (range 8-11) and 11 days (10-13), respectively. At a median follow-up of 25 months (12-40), all patients were free from signs of active lupus. Renal, cardiac, pulmonary, and serological markers, and T cell phenotype and repertoire had normalised.


CONCLUSIONS
Patients remained free from active lupus and improved continuously after transplantation, with no immunosuppressive medication or small residual doses of prednisone. T-cell repertoire diversity and responsiveness was restored. Durability of remission remains to be established.
Traynor
A E
AE
Robert H Lurie Cancer Center, Division of Immunotherapy for Autoimmune Diseases, Northwestern University, Chicago, IL, USA. a-traynor@nwu.edu
Schroeder
J
J
Rosa
R M
RM
Cheng
D
D
Stefka
J
J
Mujais
S
S
Baker
S
S
Burt
R K
RK
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000097:blood; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D001772:Blood Cell Count; D003404:Creatinine / Q000097:blood; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D037181:Lectins, C-Type; D008180:Lupus Erythematosus, Systemic / Q000628:therapy*; D008875:Middle Aged; D016896:Treatment Outcome; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018906:Antineoplastic Agents, Alkylating; D003404:Creatinine; D003520:Cyclophosphamide; D007371:Interferon-gamma; D015847:Interleukin-4; D037181:Lectins, C-Type; D000099192:CD69 Antigens