High-dose chemotherapy and syngeneic stem cell transplantation in a patient with refractory rheumatoid arthritis: poor response associated with persistence of synovial abnormalities

High-dose chemotherapy (HDC) and stem cell transplantation (SCT) is an experimental treatment option for patients with refractory rheumatoid arthritis (RA). The re-infusion of stem cells with a possible intrisic cell defect may be the cause for disease relapse despite increased sensitivity to disease-modifying anti-rheumatic drugs (DMARDs). This can be avoided by a syngeneic transplantation with healthy stem cells from an identical sibling.

We treated a 44-year-old woman, who had seropositive, erosive RA, with HDC and syngeneic SCT from her healthy identical twin sister. The patient had undergone multiple joint operations and had become refractory to conventional DMARDs, etanercept and infliximab.

Outcome measures were DAS 28, rheumatoid factor titer (IgM), need for DMARD therapy and synovial inflammation for which tissue was obtained at baseline, 2, 3 and 6 months through knee arthroscopy. Stem cells from the donor were mobilized with filgrastim and collected by leukapheresis on day -1 and 0. HDC consisted of cyclophosphamide (total dose 13.4 g intravenously) combined with 1 mg/kg prednisone. On day 0 an unmanipulated graft containing 182 × 10⁹ leukocytes, containing 769 × 10⁶ CD34⁺ cells, was administered.

HDC and syngeneic SCT did not result in remission of RA. The persistence of RF, anti-CCP (IgG) and plasma cells in the synovial tissue suggests host plasma cells were not eradicated by cyclophosphamide, nor replaced by donor plasma cells (rheumatoid factor and anti-CCP negative).