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(Circulation. 2002;105:1214.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Intravenous Pulse Administration of Cyclophosphamide Is an Effective and Safe Treatment for Sensitized Cardiac Allograft Recipients

Silviu Itescu, MD; Elizabeth Burke, RN; Katherine Lietz, MD; Ranjit John, MD; Donna Mancini, MD; Robert Michler, MD; Eric Rose, MD; Mehmet Oz, MD; Niloo Edwards, MD

From the College of Physicians and Surgeons of Columbia University, New York, NY.

Correspondence to Silviu Itescu, MD, Department of Surgery, College of Physicians & Surgeons of Columbia University, 622 W 168th St, PH 14 West, Room 1485, New York, NY 10032. E-mail si5{at}columbia.edu

Background— The proportion of cardiac transplant recipients with preexisting sensitization to HLA alloantigens has been increasing. Sensitization prolongs duration to obtaining a donor and predicts poorer long-term allograft survival because of increased risk of cellular rejections. We investigated the effect of cyclophosphamide pulse therapy in sensitized cardiac allograft recipients.

Methods and Results— Pretransplant and posttransplant outcomes were compared between 88 cardiac allograft recipients at risk for sensitization and 26 sensitized recipients treated with intravenous cyclophosphamide pulse therapy together with intravenous immune globulin before transplant and as part of a cyclosporine-based triple immunosuppressive regimen after transplant. Preformed IgG anti-HLA antibodies predicted longer duration to transplantation, earlier cellular rejection, and 2.7-fold higher cumulative rejection frequency (P=0.002). Before transplant, cyclophosphamide reduced waiting time and mortality to levels in nonsensitized patients. After transplant, cyclophosphamide prevented induction of IgG anti-HLA class II antibodies and interleukin-2 receptor–positive T-cell outgrowth from biopsy sites (both P<0.01), prolonged the rejection-free interval (P=0.009), and reduced cumulative rejections to levels in nonsensitized patients (P=0.003). By multivariable analysis, the risk of rejection was 3.7-fold higher in patients treated with mycophenolate mofetil than patients treated with cyclophosphamide (P=0.019). There were no differences in infectious or other significant complications.

Conclusions— Immunosuppression incorporating intravenous cyclophosphamide before and after transplantation is safe and highly effective in sensitized cardiac transplant recipients. When used after transplantation as part of triple immunosuppression, cyclophosphamide is superior to mycophenolate mofetil in reducing rejection. The mechanism may involve prevention of diversification of the recipient immune response to donor HLA class II molecules.

Key Words: transplantation • grafting • antigens • rejection • cells

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