Complete Immunosuppression Withdrawal and Subsequent Allograft Function Among Pediatric Recipients of Parental Living Donor Liver Transplants, January 18, 2012, Feng et al. 307 (3): 283 — JAMA

Preliminary Communication

JAMA. 2012;307(3):283-293. doi: 10.1001/jama.2011.2014

Complete Immunosuppression Withdrawal and Subsequent Allograft Function Among Pediatric Recipients of Parental Living Donor Liver Transplants

1. Sandy Feng, MD, PhD;
2. Udeme D. Ekong, MD;
3. Steven J. Lobritto, MD;
4. Anthony J. Demetris, MD;
5. John P. Roberts, MD;
6. Philip Rosenthal, MD;
7. Estella M. Alonso, MD;
8. Mary C. Philogene, PhD;
9. David Ikle, PhD;
10. Katharine M. Poole, MS;
11. Nancy D. Bridges, MD;
12. Laurence A. Turka, MD;
13. Nadia K. Tchao, MD

[+] Author Affiliations

1. Author Affiliations: Division of Transplantation, Departments of Surgery (Drs Feng, Roberts, and Rosenthal), Pediatrics (Dr Rosenthal), and Medicine (Dr Tchao), University of California, San Francisco; Department of Pediatrics, Children's Memorial Hospital, and Northwestern University Feinberg School of Medicine, Chicago, Illinois (Drs Ekong and Alonso); Departments of Pediatrics and Surgery, Morgan Stanley Children's Hospital, Columbia University Medical Center, New York, New York (Dr Lobritto); Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (Dr Demetris); Immune Tolerance Network, Bethesda, Maryland (Drs Philogene, Turka, and Tchao); Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (Dr Turka); Rho, Chapel Hill, North Carolina (Dr Ikle and Ms Poole); and Division of Allergy, Immunology, and Transplantation, National Institutes of Allergy and Infectious Diseases, Bethesda, Maryland (Dr Bridges).

Abstract

Context Although life-saving, liver transplantation burdens children with lifelong immunosuppression and substantial potential for morbidity and mortality.

Objective To establish the feasibility of immunosuppression withdrawal in pediatric living donor liver transplant recipients.

Design, Setting, and Patients Prospective, multicenter, open-label, single-group pilot trial conducted in 20 stable pediatric recipients (11 male; 55%) of parental living donor liver transplants for diseases other than viral hepatitis or an autoimmune disease who underwent immunosuppression withdrawal. Their median age was 6.9 months (interquartile range [IQR], 5.5-9.1 months) at transplant and 8 years 6 months (IQR, 6 years 5 months to 10 years 9 months) at study enrollment. Additional entry requirements included stable allograft function while taking a single immunosuppressive drug and no evidence of acute or chronic rejection or significant fibrosis on liver biopsy. Gradual immunosuppression withdrawal over a minimum of 36 weeks was instituted at 1 of 3 transplant centers between June 5, 2006, and November 18, 2009. Recipients were followed up for a median of 32.9 months (IQR, 1.0-49.9 months).

Main Outcome Measures The primary end point was the proportion of operationally tolerant patients, defined as patients who remained off immunosuppression therapy for at least 1 year with normal graft function. Secondary clinical end points included the durability of operational tolerance, and the incidence, timing, severity, and reversibility of rejection.

Results Of 20 pediatric patients, 12 (60%; 95% CI, 36.1%-80.9%) met the primary end point, maintaining normal allograft function for a median of 35.7 months (IQR, 28.1-39.7 months) after discontinuing immunosuppression therapy. Follow-up biopsies obtained more than 2 years after completing withdrawal showed no significant change compared with baseline biopsies. Eight patients did not meet the primary end point secondary to an exclusion criteria violation (n = 1), acute rejection (n = 2), or indeterminate rejection (n = 5). Seven patients were treated with increased or reinitiation of immunosuppression therapy; all returned to baseline allograft function. Patients with operational tolerance compared with patients without operational tolerance initiated immunosuppression withdrawal later after transplantation (median of 100.6 months [IQR, 71.8-123.5] vs 73.0 months [IQR, 57.6-74.9], respectively; P = .03), had less portal inflammation (91.7% [95% CI, 61.5%-99.8%] vs 42.9% [95% CI, 9.9%-81.6%] with no inflammation; P = .04), and had lower total C4d scores on the screening liver biopsy (median of 6.1 [IQR, 5.1-9.3] vs 12.5 [IQR, 9.3-16.8]; P = .03).

Conclusion In this pilot study, 60% of pediatric recipients of parental living donor liver transplants remained off immunosuppression therapy for at least 1 year with normal graft function and stable allograft histology.

Complete Immunosuppression Withdrawal and Subsequent Allograft Function Among Pediatric Recipients of Parental Living Donor Liver Transplants, January 18, 2012, Feng et al. 307 (3): 283 — JAMA