By David N. Leff
Stem cells have come to the rescue of seven women with aggressive, life-threatening systemic lupus erythematosus (SLE).
Two years after the landmark therapy began in 1996, all seven patients were free from signs of active SLE, and their besieged kidney, heart, lung and immune system functions had become normal.
An article in the current issue of Lancet, dated Aug. 26, 2000, sums up the feat in its title: "Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and hematopoietic stem-cell transplantation: a Phase I study." The paper's lead author, clinician Ann Traynor, is a physician/researcher in bone-marrow transplantation at Northwestern University's Memorial Hospital in Chicago.
Although billed as a Phase I safety and efficacy trial, her team's clinical experiment actually reported results such as are seen in Phase II and III efficacy studies.
Of the more than one million SLE patients in the U.S. today, some 200,000 have advanced multiple-organ failures, wrought by inflammatory autoimmune antibodies. Between 10 and 15 percent die within a decade of diagnosis.
These friendly-fire T-cell antibodies couple to their phalanxes of organ-targeting antigens, and gum up the inner walls of small blood vessels. This stimulates the cell-destroying complement system to damage those blood vessels, which results in vasculitis and glomerulonephritis.
Current therapy treats each ravaged organ, in particular the kidneys, symptomatically, while attempting to cut back on the pile-up of marauding autoantibodies by high-dose immunosuppressive drugs, primarily prednisone or intravenous cyclophosphamide. This, of course, weakens the patient's immune defenses against opportunistic infections. (See BioWorld Today, April 27, 2000, p. 1.)
The seven women that Traynor and her co-authors invited into their stem-cell therapeutic effort ranged in age from 15 to 51, with duration of disease from less than one year to 20 years. All seven suffered fatigue and depression, typical of SLE, and four had intractable, recurrent headaches. Two of the latter were subject to epileptic seizures.
They had varied organ inflammation - of kidneys (glomerulonephritis), brain (lupus cerebritis), spinal cord (transverse myelitis), heart or lung (lupus vasculitis), and other severe syndromes. All were deemed at high risk of early death.
The treatment started with the patients donating hematopoietic stem cells from their blood, via leucopheresis collection. These cells were stored for later retransplantation. Treatment throughout featured very high-dose, intensive cyclophosphamide, supplemented by antifungal and antiviral screens to forefend infection. Two patients developed herpes zoster two months after completing the treatment regimen, and one contracted Pneumocystis carinii at day 60, which was treated successfully.
"Lupus remained in clinical remission in all patients," the Lancet paper stated, "and there was no evidence of active disease, as defined by symptoms or findings of serositis, synovitis, cerebritis or glomerulonephritis. No patient had a disease flare after tranplantation."
It summed up "long-term follow-up in the seven patients: two patients for more than three years and all beyond one year. Disease activity was stopped and organ function strikingly improved concurrent with tapering or discontinuation of immunosuppressive treatment."
Traynor, the paper's lead author, commented in a press release: "What is exciting about this observation is that it appears that the immune system can correct its errors if early stem cells are allowed to mature as naove cells in a 'neutral' environment. This new generation of immune cells is not destined to repeat the ruinous errors of the prior generations."