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(Circulation. 1999;100:II-229.)
© 1999 American Heart Association, Inc.

Thoracic Transplantation and Ventricular Assist Devices

Intravenous Immunoglobulin Reduces Anti-HLA Alloreactivity and Shortens Waiting Time to Cardiac Transplantation in Highly Sensitized Left Ventricular Assist Device Recipients

Ranjit John, MD; Katherine Lietz, MD, PhD; Elizabeth Burke, RN; Jan Ankersmit, MD; Donna Mancini, MD; Nicole Suciu-Foca, PhD; Niloo Edwards, MD; Eric Rose, MD; Mehmet Oz, MD; Silviu Itescu, 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 and Surgeons of Columbia University, 622 W 168th St, PH 14 W, Room 1485, New York, NY 10032.

Background—Recipients of left ventricular assist devices (LVADs) develop prominent B-cell hyperreactivity. We investigated the influence of anti-HLA antibodies on waiting time to cardiac transplantation in LVAD recipients and compared the effects of 2 immunomodulatory regimens on anti-HLA serum reactivity.

Methods and Results—Fifty-five previously nonsensitized LVAD recipients of a TCI device implanted between 1990 and 1996 were studied. Patients with anti-HLA antibodies received monthly courses of either intravenous immunoglobulin (IVIg) or plasmapheresis, in conjunction with cyclophosphamide. The effects of these regimens on anti-HLA alloreactivity and waiting time to transplantation were then determined by Kaplan-Meier log-rank statistics, nonparametric Wilcoxon rank-sum test, and Student’s t test. Prolongation in transplant waiting time was related to serum IgG anti–HLA class I alloreactivity. Infusion of IVIg (2 g/kg) caused a mean reduction of 33% in anti–HLA class I alloreactivity within 1 week. Waiting time to transplantation was significantly reduced by IVIg therapy and subsequently approximated that in nonsensitized patients. Side effects of IVIg (2 g/kg) were minimal and related primarily to immune complex disease. Although plasmapheresis caused a similar reduction in alloreactivity to IVIg, this effect was achieved after longer treatment. Moreover, plasmapheresis was associated with an unacceptably high frequency of infectious complications. In patients resistant to low-dose (2 g/kg) IVIg therapy, high-dose (3 g/kg) IVIg was effective in reducing alloreactivity but was associated with a high incidence of reversible renal insufficiency.

Conclusions—These results indicate that IVIg is an effective and safe modality for sensitized recipients awaiting cardiac transplantation, reducing serum anti-HLA alloreactivity and shortening the duration to transplantation. The therapeutic and safety profile of IVIg would appear to be superior to plasmapheresis.

Key Words: antibodies • immune system • transplantation • ventricular assist devices