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Blood, 1 February 2002, Vol. 99, No. 3, pp. 768-784
REVIEW ARTICLE
Induction of tolerance in autoimmune diseases by hematopoietic
stem cell transplantation: getting closer to a cure?
Richard K. Burt,
Shimon Slavin,
William H. Burns, and
Alberto M. Marmont
From the Northwestern University Medical Center,
Division of Immune Therapy and Autoimmune Disease, Chicago, IL;
Department of Bone Marrow Transplantation & Cancer Immunotherapy,
Hadassah University Hospital, Jerusalem, Israel; Bone Marrow
Transplantation, Medical College of Wisconsin, Milwaukee; Divisione di
Ematologia II, Centro Trapianti di Midollo Osseo, Azienda Ospedaliera
S. Martino, Genoa, Italy.
Hematopoietic stem cells (HSCs) are the earliest cells of the
immune system, giving rise to B and T lymphocytes, monocytes, tissue
macrophages, and dendritic cells. In animal models, adoptive transfer
of HSCs, depending on circumstances, may cause, prevent, or cure
autoimmune diseases. Clinical trials have reported early remission of
otherwise refractory autoimmune disorders after either autologous or
allogeneic hematopoietic stem cell transplantation (HSCT). By
percentage of transplantations performed, autoimmune diseases are the
most rapidly expanding indication for stem cell transplantation.
Although numerous editorials or commentaries have been previously
published, no prior review has focused on the immunology of
transplantation tolerance or development of phase 3 autoimmune HSCT
trials. Results from current trials suggest that mobilization of HSCs,
conditioning regimen, eligibility and exclusion criteria, toxicity,
outcome, source of stem cells, and posttransplantation follow-up need
to be disease specific. HSCT-induced remission of an autoimmune disease
allows for a prospective analysis of events involved in immune
tolerance not available in cross-sectional studies.
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