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(Circulation. 2007;116:I-172 – I-178.)
© 2007 American Heart Association, Inc.

Surgery for Congenital Heart Disease

Pediatric Heart Transplantation in Human Leukocyte Antigen–Sensitized Patients

Evolving Management and Assessment of Intermediate-Term Outcomes in a High-Risk Population

Stacey M. Pollock-BarZiv, PhD; Neal den Hollander, MD; Bo-Yee Ngan, MD; Paul Kantor, MD; Brian McCrindle, MD; Lori J. West, MD, DPhil; Anne I. Dipchand, MD

From the Department of Pediatrics (S.M.P.-B., P.K., B.M., A.I.D.), Division of Cardiology, The Hospital for Sick Children/University of Toronto, Toronto, Ontario, Canada; Histocompatibility Laboratory (N.d.H.), University Health Network, Toronto, Ontario, Canada; Department of Pediatrics (B.-Y.N.), Division of Pathology, The Hospital for Sick Children/University of Toronto, Toronto, Ontario, Canada; and Departments of Pediatrics, Surgery, and Immunology (L.J.W.), University of Alberta, Edmonton, Alberta, Canada.

Correspondence to Anne I. Dipchand, MD, The Hospital for Sick Children, Division of Cardiology, Head, Heart Transplant Service, 555 University Ave, Toronto, Ontario M5G 1X8. E-mail anne.dipchand{at}sickkids.ca

Background— There is an elevated risk for poor outcomes after heart transplant (HTx) in patients sensitized to human leukocyte antigens including graft dysfunction, acute cellular and antibody-mediated (AMR) rejection, and cardiac allograft vasculopathy. We report our experience with human leukocyte antigens–sensitized pediatric HTx recipients.

Methods and Results— We identified pediatric HTx patients with elevated pre-HTx Panel Reactive Antibody (Class I/II; >10%), or a positive T- or B-cell crossmatch. Thirteen patients met criteria (5 female, 39%). The median age at HTx was 7 months (3.5 months to 15.5 years). Nine were infants who had prior palliation for congenital heart disease. Four were older patients (median 7.3 years; 4.8 to 15.5 years): 2 had congenital heart disease (Fontan), 2 were re-HTx. B-cell therapies were used in all patients, guided by assessment of CD19+ and CD20+ cells. Immunosuppression included thymoglobulin induction, and tacrolimus, mycophenolate mofetil, and steroids. Daily plasmapheresis ± intravenous immunoglobulin G was used if there was a positive crossmatch on day 1, with a gradual, biopsy-guided weaning schedule. Rituximab was used when AMR was detected on biopsy: more recently (n=3), used empirically perioperatively. AMR was confirmed in 9 patients within median 0.9 months post-HTx. Seven had early acute cellular rejection ( ISHLT Grade 2 R) with no hemodynamic compromise or graft dysfunction. There were 4 deaths post-HTx (range, 11 days to 9 months). The median follow-up of 9 survivors was 1.7 years (0.3 to 3.7 years). Of 7 patients >6 months post-HTx, no AMR or cardiac allograft vasculopathy was observed at a mean of 1.9+1.1 years post-HTx and no cardiac allograft vasculopathy.

Conclusions— Despite aggressive management, acute cellular rejection and AMR occurred frequently early post-HTx. An algorithm of B cell–directed strategies can be effective in managing these patients with reasonable intermediate-term outcomes.

Key Words: pediatric • heart transplantation • HLA-antibodies • sensitization • outcomes