Rk. Burt et al., TREATMENT OF AUTOIMMUNE-DISEASE BY INTENSE IMMUNOSUPPRESSIVE CONDITIONING AND AUTOLOGOUS HEMATOPOIETIC STEM-CELL TRANSPLANTATION, Blood, 92(10), 1998, pp. 3505-3514
Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthr
itis are immune-mediated diseases that are responsive to suppression o
r modulation of the immune system. For patients with severe disease, i
mmunosuppression may be intensified to the point of myelosuppression o
r hematopoietic ablation. Hematopoiesis and immunity may then be rapid
ly reconstituted by reinfusion of CD34(+) progenitor cells. In 10 pati
ents with these autoimmune diseases, autologous hematopoietic stem cel
ls were collected from bone marrow or mobilized from peripheral blood
with either granulocyte colony-stimulating factor (G-CSF) or cyclophos
phamide and G-CSF. Stem cells were enriched ex vivo using CD34(+) sele
ction and reinfused after either myelosuppressive conditioning with cy
clophosphamide (200 mg/kg), methylprednisolone (4 g) and antithymocyte
globulin (ATG; 90 mg/kg) or myeloablative conditioning with total bod
y irradiation (1,200 cGy), methylprednisolone (4 g), and cyclophospham
ide (120 mg/kg). Six patients with multiple sclerosis, 2 with systemic
lupus erythematosus, and 2 with rheumatoid arthritis have undergone h
emtopoietic stem cell transplantation. Mean time to engraftment of an
absolute neutrophil count greater than 500/mu L (0.5 x 10(9)/L) and a
nontransfused platelet count greater than 20,000/mu L (20 x 10(9)/L) o
ccurred on day 10 and 14, respectively. Regimen-related nonhematopoiet
ic toxicity was minimal. All patients improved and/or had stabilizatio
n of disease with a follow-up of 5 to 17 months (median, 11 months). W
e 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 stabili
zation or improvement. (C) 1998 by The American Society of Hematology.