|
NEW YORK (Reuters Health) Jan 31 - In patients with severe systemic
lupus erythematosus (SLE), autologous nonmyeloablative hematopoietic
stem cell transplantation (HSCT) stabilizes or even reverses organ
dysfunction, investigators report in the Journal of the American
Medical Association for February 1.
"We believed we could perhaps regenerate the immune system using
HSCT in people who have severe, life-threatening and organ-threatening
autoimmune disorders and who had failed all other therapies available," lead
author Dr. Richard K. Burt told Reuters Health.
Between 1997 and 2005, Dr. Richard K. Burt and his colleagues
at Northwestern University Feinberg School of Medicine in Chicago
recruited 50 patients with SLE refractory to standard immunosuppressive
therapies and who had either organ- or life-threatening visceral
involvement.
Peripheral blood stem cells were mobilized with cyclophosphamide
and granulocyte colony-stimulating factor. Leukapheresis was performed
and cells were enriched ex vivo by CD34+ immunoselection, which
were cryopreserved until after the conditioning treatment.
The patients were then treated with a conditioning regimen of
cyclophosphamide and antithymocyte globulin to eliminate self-reactive
lymphocytes. Patients were treated with antibiotic prophylaxis
during and following HSCT.
"The purpose was to use a conditioning regimen -- chemotherapy
-- to destroy the immune system and then use stem cells to rebuild
a new one," Dr. Burt explained.
Two patients died before undergoing HSCT. Among the remainder,
there were no treatment-related deaths.
The authors note that HSCT had a disease-ameliorating effect.
The probability of 5-year survival was 84%, while disease-free
survival was 50%. The longest duration of survival so far has been
7.5 years.
There was also significant improvement in secondary endpoints:
SLE Disease Activity Index, lupus serology, pulmonary function,
complement, immune-mediated hemolysis and thrombocytopenia, and
thrombotic effects. No new cases of nephritis developed, and those
with pre-transplant nephritis generally improved.
HSCT is not without its own risks, so it's important to weigh
risks and benefits when selecting patients for HCST, Dr. Burt noted. "You
have to choose patients whose risk of lethality from disease is
greater than that from the treatment."
He added that his group hopes to soon start a randomized clinical
trial of autologous HSCT compared with continued standard treatment
in SLE patients. They are also considering a trial of allogeneic
HSCT, based on the theory that they could "change the genetic predisposition
of immune cells in their response to self-antigen."
In a related editorial, Drs. Michelle Petri and Robert Brodsky,
from Johns Hopkins University School of Medicine in Baltimore,
laud the substantial benefit that most patients experienced, but
note that patients successfully treated with HSCT may have late
relapses.
"Whether this approach represents a definitive advance over more
conventional immunosuppressive therapies will need to be answered
in randomized controlled trials," they add.
|
Message
Boards
