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Favorable Outcome of an Exclusively Posttransplant Prophylactic Strategy After Heart Transplantation in Recipients With High Immunological Risk

Coutance, Guillaume MD1; d’Orio, Virginie MD1,2; Belin, Lisa PhD3; Bréchot, Nicolas MD, PhD4,5; Saheb, Samir MD6; Lebreton, Guillaume MD, PhD1; Bouglé, Adrien MD7; Rouvier, Philippe MD8; Gautreau, Chantal MD9; Ouldammar, Salima MD1; Chamillard, Xavier MD10; Huot, Mélanie PharmD11; Amour, Julien MD, PhD7; Combes, Alain MD, PhD4,5; Leprince, Pascal MD, PhD1; Varnous, Shaida MD1

doi: 10.1097/TP.0000000000002503
Original Clinical Science—General
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Background. Management of the increasing number of sensitized heart transplant candidates has become a recurrent issue. Rather than using pretransplant desensitization therapies, we used a posttransplant prophylactic strategy. Our aim was to describe outcomes in transplant recipients with preformed donor-specific anti-HLA antibodies (pfDSA) managed with this strategy.

Methods. A posttransplant protocol was applied to patients transplanted with pfDSA, consisting of perioperative management of DSA (polyvalent immunoglobulins +/− perioperative plasmapheresis sessions, according to DSA level, as well as induction therapy) and systematic treatment of subsequent antibody-mediated rejection (AMR), even when subclinical. We performed a retrospective analysis of this prospective protocol. The study included all consecutive first recipients of a noncombined heart transplant performed between 2009 and 2015 at our center. The primary endpoint was all-cause mortality. Secondary endpoints included primary graft dysfunction, early posttransplant bleeding, rejection, and cardiac allograft vasculopathy-free survival.

Results. A total of 523 patients were studied, including 88 (17%) and 194 (37%) transplanted with DSA mean fluorescence intensity (MFI) of 500 to 1000 and greater than 1000, respectively. The median follow-up period was 4.06 years. Survival was not significantly different between groups. Rejection-free survival was worse in patients with pfDSA MFI >1000, evidenced by a fourfold increase in the risk of antibody-mediated rejection. The incidence of primary graft dysfunction and cardiac allograft vasculopathy-free survival did not significantly differ between groups. Perioperative plasmapheresis increased the risk for transfusion of packed red blood cells.

Conclusions. This exclusively posttransplant prophylactic strategy achieved favorable outcomes in heart transplant recipients with pfDSA.

1 Department of Cardiac and Thoracic Surgery, Cardiology Institute, Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP). Sorbonne University Medical School, Paris, France.

2 Department of Cardiology, University Hospital, Liège, Belgium.

3 Department of Biotatistics, Public Health and Health Information, Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP). Sorbonne University Medical School, Paris, France.

4 Department of Medical Intensive Care Unit, Cardiology Institute, Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP). Sorbonne University Medical School, Paris, France.

5 INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Paris, France.

6 Department of Hemo-Biotherapies, Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP). Sorbonne University Medical School, Paris, France.

7 Sorbonne Université, UMR INSERM 1166, IHU ICAN, Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, Cardiology Institute, Pitié-Salpêtrière Hospital, Paris.

8 Department of Pathology, Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP). Sorbonne University Medical School, Paris, France.

9 Laboratory of Immunology and Histocompatibility, AP-HP, Saint Louis Hospital, Paris, France.

10 Etablissement Français du Sang, Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP). Sorbonne University Medical School, Paris, France.

11 Department of Pharmacy, Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP). Sorbonne University Medical School, Paris, France.

Received 16 July 2018. Revision received 7 September 2018.

Accepted 23 September 2018.

G.C. received research grants from the ADICARE association (2017).

The authors declare no conflicts of interest.

G.C. participated in the performance of the research, in data analysis and in the writing of the article. V.d’.O. participated in the performance of the research and in data analysis. L.B. participated in data analysis and in the writing of the article. N.B. participated in research design and in the performance of the research. S.S. participated in research design and in the performance of the research. G.L. participated in research design and in the writing of the article. A.B. participated in the performance of the research and in the writing of the article. P.R. participated in the performance of the research and in the writing of the article. C.G. participated in the performance of the research and in the writing of the article. S.O. participated in the performance of the research. X.C. participated in the performance of the research. M.H. participated in the performance of the research. J.A. participated in research design and in the writing of the article. A.C. participated in research design and in the writing of the article. P.L. participated in research design and in the writing of the article. S.V. participated in research design and in the writing of the article.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

Correspondence: Guillaume Coutance, MD, Service de Chirurgie Thoracique et Cardio-Vasculaire, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, 47-83, boulevard de l’Hôpital, 75651 Paris Cedex 13, France. (guillaume.coutance@gmail.com).

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