High-dose cyclophosphamide in multiple sclerosis patients undergoing autologous stem cell transplantation.

High-dose cyclophosphamide (CTX) is commonly used in preparation for autologous and allogeneic stem cell transplantation. CTX is a pro-drug, which undergoes complex oxidative metabolism with the metabolites being eliminated both renally and hepatically. In the following study, we evaluated the pharmacokinetic characteristics of high-dose CTX in three patients undergoing autologous stem cell transplantation for multiple sclerosis. The plasma concentration-time profiles for CTX and its hydroxy-metabolite were similar in multiple sclerosis patients to those reported in cancer patients undergoing stem cell transplantation. There was an increase in drug clearance after the second CTX dose indicating that the drug induced its own metabolism consistent with reports in other populations receiving high-dose CTX. One of the three patients cleared the drug slowly but this was not associated with greater toxicity. The patient with the slow clearance value and therefore highest drug exposure had stable disability scores at 2 years posttransplant compared with baseline values taken prior to transplantation. In conclusion, in this small case series, there was no indication that CTX metabolism was different than that in other populations undergoing transplantation.

Intensive immunoablation and autologous blood stem cell transplantation in patients with refractory rheumatoid arthritis: the University of Nebraska experience.

Two patients with severe rheumatoid arthritis (RA) were treated with high dose chemotherapy and autologous blood stem cell transplantation. Hematopoietic stem cells mobilized readily with cyclophosphamide and granulocyte-colony stimulating factor. Both patients achieved an American College of Rheumatology (ACR) 50% response before starting high dose therapy. The transplantation regimen included 200 mg/kg cyclophosphamide and 6 doses of equine antithymocyte globulin. Transplantation was well tolerated and both patients recovered neutrophils on day 7 post-transplant. At one month post-transplant both patients had an ACR response of 80%. Both individuals relapsed at 6 months and responded well to a combination of disease modifying antirheumatic drugs that was previously ineffective. At 12 months ACR responses were 80% and 60%, respectively. The first patient developed a flare at 18 months when she was found to be hypothyroid; she regained an 80% ACR response at 24 months with therapy of hypothyroidism. The second patient progressed relentlessly 15 months post-transplant. Immunological reconstitution showed a continuous inversion of the ratio of CD4 and CD8 lymphocytes with a predominant expansion of memory T cells.