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

Ann E. Traynor*, James Schroeder, Robert M. Rosa, Dong Cheng, Jakub Stefka, Salim Mujais, Steven Baker, Richard K. Burt

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

211 Scopus citations

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 μg/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 0·5x109/L and nontransfused platelet count higher than 20x109/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 tranplantation, 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.

Original languageEnglish (US)
Pages (from-to)701-707
Number of pages7
JournalLancet
Volume356
Issue number9231
DOIs
StatePublished - Aug 26 2000

ASJC Scopus subject areas

  • Medicine(all)

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