Heart-After-Liver Transplantation Attenuates Rejection of Cardiac Allografts in Sensitized Patients.


Journal

Journal of the American College of Cardiology
ISSN: 1558-3597
Titre abrégé: J Am Coll Cardiol
Pays: United States
ID NLM: 8301365

Informations de publication

Date de publication:
16 03 2021
Historique:
received: 14 10 2020
revised: 07 01 2021
accepted: 08 01 2021
entrez: 12 3 2021
pubmed: 13 3 2021
medline: 1 10 2021
Statut: ppublish

Résumé

In patients undergoing heart transplantation, significant allosensitization limits access to organs, resulting in longer wait times and high waitlist mortality. Current desensitization strategies are limited in enabling successful transplantation. The purpose of this study was to describe the cumulative experience of combined heart-liver transplantation using a novel heart-after-liver transplant (HALT) protocol resulting in profound immunologic protection. Reported are the results of a clinical protocol that was instituted to transplant highly sensitized patients requiring combined heart and liver transplantation at a single institution. Patients were dual-organ listed with perceived elevated risk of rejection or markedly prolonged waitlist time due to high levels of allo-antibodies. Detailed immunological data and long-term patient and graft outcomes were obtained. A total of 7 patients (age 43 ± 7 years, 86% women) with high allosensitization (median calculated panel reactive antibody = 77%) underwent HALT. All had significant, unacceptable donor specific antibodies (DSA) (>4,000 mean fluorescence antibody). Prospective pre-operative flow cytometric T-cell crossmatch was positive in all, and B-cell crossmatch was positive in 5 of 7. After HALT, retrospective crossmatch (B- and T-cell) became negative in all. DSA fell dramatically; at last follow-up, all pre-formed or de novo DSA levels were insignificant at <2,000 mean fluorescence antibody. No patients experienced >1R rejection over a median follow-up of 48 months (interquartile range: 25 to 68 months). There was 1 death due to metastatic cancer and no significant graft dysfunction. A heart-after-liver transplantation protocol enables successful transplantation via near-elimination of DSA and is effective in preventing adverse immunological outcomes in highly sensitized patients listed for combined heart-liver transplantation.

Sections du résumé

BACKGROUND
In patients undergoing heart transplantation, significant allosensitization limits access to organs, resulting in longer wait times and high waitlist mortality. Current desensitization strategies are limited in enabling successful transplantation.
OBJECTIVES
The purpose of this study was to describe the cumulative experience of combined heart-liver transplantation using a novel heart-after-liver transplant (HALT) protocol resulting in profound immunologic protection.
METHODS
Reported are the results of a clinical protocol that was instituted to transplant highly sensitized patients requiring combined heart and liver transplantation at a single institution. Patients were dual-organ listed with perceived elevated risk of rejection or markedly prolonged waitlist time due to high levels of allo-antibodies. Detailed immunological data and long-term patient and graft outcomes were obtained.
RESULTS
A total of 7 patients (age 43 ± 7 years, 86% women) with high allosensitization (median calculated panel reactive antibody = 77%) underwent HALT. All had significant, unacceptable donor specific antibodies (DSA) (>4,000 mean fluorescence antibody). Prospective pre-operative flow cytometric T-cell crossmatch was positive in all, and B-cell crossmatch was positive in 5 of 7. After HALT, retrospective crossmatch (B- and T-cell) became negative in all. DSA fell dramatically; at last follow-up, all pre-formed or de novo DSA levels were insignificant at <2,000 mean fluorescence antibody. No patients experienced >1R rejection over a median follow-up of 48 months (interquartile range: 25 to 68 months). There was 1 death due to metastatic cancer and no significant graft dysfunction.
CONCLUSIONS
A heart-after-liver transplantation protocol enables successful transplantation via near-elimination of DSA and is effective in preventing adverse immunological outcomes in highly sensitized patients listed for combined heart-liver transplantation.

Identifiants

pubmed: 33706876
pii: S0735-1097(21)00078-4
doi: 10.1016/j.jacc.2021.01.013
pii:
doi:

Types de publication

Journal Article Observational Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

1331-1340

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Auteurs

Richard C Daly (RC)

Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota, USA.

Andrew N Rosenbaum (AN)

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.

Joseph A Dearani (JA)

Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota, USA.

Alfredo L Clavell (AL)

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.

Naveen L Pereira (NL)

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.

Barry A Boilson (BA)

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.

Robert P Frantz (RP)

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.

Atta Behfar (A)

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA; VanCleve Cardiac Regenerative Medicine Program, Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Shannon M Dunlay (SM)

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.

Richard J Rodeheffer (RJ)

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.

John A Schirger (JA)

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.

Timucin Taner (T)

Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA; Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.

Manish J Gandhi (MJ)

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.

Julie K Heimbach (JK)

Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

Charles B Rosen (CB)

Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.

Brooks S Edwards (BS)

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.

Sudhir S Kushwaha (SS)

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA. Electronic address: Kushwaha.sudhir@mayo.edu.

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Classifications MeSH