Stem Cell Support in Patients With Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic illness, immunologically mediated, probably induced
by the exposure to an antigen or antigens, to which immunologic tolerance is lost. The
disease has a variable course, from a mild, intermittently symptomatic illness requiring
only symptomatic therapy to a fulminant illness requiring dangerous immunosuppressive
therapy, surgery or both. The molecular defect causing RA has not been characterized, but
may involve aberrant T cell, B cell, and macrophage function. Although RA often responds to
immunosuppressive medication including corticosteroids, methotrexate, azathioprine and
cyclophosphamide, or to non-steroidal anti-inflammatory drugs, no therapy has been curative.
In patients with severe RA, who have been unresponsive to corticosteroids, and who have more
than 20 active joints or vasculitis, we propose, as a phase I-II study, complete immune
ablation and subsequent reconstitution with autologous in vitro T lymphocyte depleted PBSCs
harvested from the patient prior to immune ablation. The combination of high dose
cyclophosphamide and anti-thymocyte globulin conditioning will be followed by rescue with
autologous lymphocyte depleted PBSCs. Subsequent disease activity will be followed by: (1)
RA disease activity index, (2) type and amount of therapy for RA, and (3) flow cytometry of
peripheral blood lymphocyte subsets, (4) joint count, (5) patients' assessment of pain, (6)
arthritis impact measurement scales (AIMS) questionnaire, (7) acute phase reactants. This
study will dose standard therapy, i.e. immune suppression, to the point of complete immune
ablation and subsequent recapitulation of lymphocyte ontogeny by PBSC rescue. We anticipate
that this study will also form the basis to clarify further the role of the immune system in
RA.