Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study

Lancet. 2000 Aug 26;356(9231):701-7. doi: 10.1016/S0140-6736(00)02627-1.

Abstract

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.

Interpretation: 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD / blood
  • Antigens, Differentiation, T-Lymphocyte / blood
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / immunology
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Blood Cell Count
  • Creatinine / blood
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / immunology
  • Cyclophosphamide / therapeutic use*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Interferon-gamma / blood
  • Interleukin-4 / blood
  • Lectins, C-Type
  • Lupus Erythematosus, Systemic / therapy*
  • Middle Aged
  • Treatment Outcome

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Antineoplastic Agents, Alkylating
  • CD69 antigen
  • Lectins, C-Type
  • Interleukin-4
  • Interferon-gamma
  • Cyclophosphamide
  • Creatinine