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Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3505-3514
RAPID COMMUNICATION
Treatment of Autoimmune Disease by Intense Immunosuppressive
Conditioning and Autologous Hematopoietic Stem Cell Transplantation
Richard K. Burt,
Ann E. Traynor,
Richard Pope,
James Schroeder,
Bruce Cohen,
Karyn H. Karlin,
Lorri Lobeck,
Charles Goolsby,
Philip Rowlings,
Floyd A. Davis,
Dusan Stefoski,
Cass Terry,
Carolyn Keever-Taylor,
Steve Rosen,
David Vesole,
Maryanne Fishman,
Mary Brush,
Salim Mujias,
Marcelo Villa, and
William H. Burns
From the Departments of Medicine, Neurology, Nephrology, and
Rheumatology, Division of Hematology/Oncology & Lurie Comprehensive
Cancer Center, Northwestern University Medical School and Robert H. Lurie Cancer Center, Chicago, IL; Rush Presbyterian St Luke's Medical
Center, Multiple Sclerosis Center and Department of Neurology, Chicago,
IL; and the Departments of Neurology and Medicine, Division of
Hematology/Oncology, Medical College of Wisconsin, Milwaukee,
WI.
Multiple sclerosis, systemic lupus erythematosus, and rheumatoid
arthritis are immune-mediated diseases that are responsive to
suppression or modulation of the immune system. For patients with
severe disease, immunosuppression may be intensified to the point of
myelosuppression or hematopoietic ablation. Hematopoiesis and immunity
may then be rapidly reconstituted by reinfusion of CD34+
progenitor cells. In 10 patients with these autoimmune diseases, autologous hematopoietic stem cells were collected from bone marrow or
mobilized from peripheral blood with either granulocyte
colony-stimulating factor (G-CSF) or cyclophosphamide and G-CSF. Stem
cells were enriched ex vivo using CD34+ selection and
reinfused after either myelosuppressive conditioning with
cyclophosphamide (200 mg/kg), methylprednisolone (4 g) and antithymocyte globulin (ATG; 90 mg/kg) or myeloablative conditioning with total body irradiation (1,200 cGy), methylprednisolone (4 g), and
cyclophosphamide (120 mg/kg). Six patients with multiple sclerosis, 2 with systemic lupus erythematosus, and 2 with rheumatoid arthritis have
undergone hematopoietic stem cell transplantation. Mean time to
engraftment of an absolute neutrophil count greater than 500/µL (0.5 × 109/L) and a nontransfused platelet count greater than
20,000/µL (20 × 109/L) occurred on day 10 and 14, respectively. Regimen-related nonhematopoietic toxicity was minimal.
All patients improved and/or had stabilization of disease with
a follow-up of 5 to 17 months (median, 11 months). We conclude that
intense immunosuppressive conditioning and autologous T-cell-depleted
hematopoietic transplantation was safely used to treat these 10 patients with severe autoimmune disease. Although durability of
response is as yet unknown, all patients have demonstrated stabilization or improvement.
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