Intensified-dose (4 gm/m(2)) cyclophosphamide and granulocyte colony-stimulating factor administration for hematopoietic stem cell mobilization in refractory rheumatoid arthritis

Objective. To evaluate the feasibility, safety, and efficacy of intensified -dose cyclophosphamide (ID-CYC), followed by granulocyte colony-stimulating factor (G-CSF) administration for collection of peripheral blood hematopoi etic stem cells (HSC), for patients with severe, refractory rheumatoid arth ritis (RA). Methods. Four patients with severe refractory RA were enrolled in this open study. They received a single infusion of CYC (4 gm/m(2)) at day 0 followe d by G-CSF (5 mu g/kg/day) from day 6 until the last day of leukapheresis ( performed at the time of hematopoietic recovery) to harvest peripheral bloo d HSC, Patients were monitored for disease activity, adverse effects, and h ematopoietic reconstitution following this procedure. Results. For all patients, administration of ID-CYC induced an early, drama tic improvement of disease activity. Long-term followup indicates that part ial disease relapse was observed for all patients. No adverse effect was di rectly attributable to the treatment procedure. For most patients, HSC coll ection was sufficient to provide a graft enriched in CD34+ cells by positiv e selection as well as an unselected rescue graft. Conclusion. Patients with severe, refractory RA can benefit from ID-CYC, Th is procedure, followed by G-CSF administration, appears safe and technicall y suitable. In addition, it allows immediate improvement of RA activity tha t can occasionally persist beyond 6 months.