. 2025 Jul 3:16:1631525.

doi: 10.3389/fimmu.2025.1631525. eCollection 2025.

What are the functional outcomes of total laryngeal transplantation? A systematic review of preclinical and clinical studies

Douglas Henderson^#^{1

2}, Leonard Knoedler^#^{3

4}, Tobias Niederegger³, Jakob Fenske³, Olivier Mathieu⁴, Gabriel Hundeshagen^{5

6}, Max Heiland³, Curtis L Cetrulo Jr⁴, D Gregory Farwell⁷, Jerome R Lechien^{8

9}, Alexandre G Lellouch^{4

10

11

12}

Affiliations

¹ Faculty of Medicine, Université Paris Cité, Paris, France.
² Department of ENT and Head and Neck Surgery, Lariboisière Hospital, AP-HP, Paris, France.
³ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Oral and Maxillofacial Surgery, Berlin, Germany.
⁴ Division of Plastic and Reconstructive Surgery, Cedars-Sinai Hospital, Los Angeles, CA, United States.
⁵ Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma HospitalLudwigshafen, Ludwigshafen, Germany.
⁶ Department of Plastic and Hand Surgery, University of Heidelberg, Ludwigshafen, Germany.
⁷ Department of Otorhinolaryngology-Head and Neck Surgery, Hospital of the University of Pennsylvania and Perelman School of Medicine, Philadelphia, PA, United States.
⁸ Department of Surgery, University of Mons, Mons, Belgium.
⁹ Department of Otolaryngology-Head Neck Surgery, Foch Hospital, University of Paris Saclay, Paris, France.
¹⁰ Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
¹¹ Université Paris Cité, Inserm, The Paris Cardiovascular Research Center, Team Endotheliopathy and Hemostasis Disorders, Paris, France.
¹² AP-HP, Hôpital Européen Georges Pompidou, Hematology Department, Paris, France.

^# Contributed equally.

PMID: 40677707
PMCID: PMC12267005
DOI: 10.3389/fimmu.2025.1631525

What are the functional outcomes of total laryngeal transplantation? A systematic review of preclinical and clinical studies

Douglas Henderson et al. Front Immunol. 2025.

. 2025 Jul 3:16:1631525.

doi: 10.3389/fimmu.2025.1631525. eCollection 2025.

Authors

Affiliations

¹ Faculty of Medicine, Université Paris Cité, Paris, France.
² Department of ENT and Head and Neck Surgery, Lariboisière Hospital, AP-HP, Paris, France.
³ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Oral and Maxillofacial Surgery, Berlin, Germany.
⁴ Division of Plastic and Reconstructive Surgery, Cedars-Sinai Hospital, Los Angeles, CA, United States.
⁵ Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma HospitalLudwigshafen, Ludwigshafen, Germany.
⁶ Department of Plastic and Hand Surgery, University of Heidelberg, Ludwigshafen, Germany.
⁷ Department of Otorhinolaryngology-Head and Neck Surgery, Hospital of the University of Pennsylvania and Perelman School of Medicine, Philadelphia, PA, United States.
⁸ Department of Surgery, University of Mons, Mons, Belgium.
⁹ Department of Otolaryngology-Head Neck Surgery, Foch Hospital, University of Paris Saclay, Paris, France.
¹⁰ Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
¹¹ Université Paris Cité, Inserm, The Paris Cardiovascular Research Center, Team Endotheliopathy and Hemostasis Disorders, Paris, France.
¹² AP-HP, Hôpital Européen Georges Pompidou, Hematology Department, Paris, France.

^# Contributed equally.

PMID: 40677707
PMCID: PMC12267005
DOI: 10.3389/fimmu.2025.1631525

Abstract

Purpose: This systematic review aims to evaluate the functional outcomes of total laryngeal transplantation by synthesizing findings from both preclinical and clinical studies. It focuses on assessing postoperative functional recovery, including swallowing, airway patency, phonation, and speech, while also considering the associated morbidities and immunosuppressive strategies.

Methods: A systematic review was conducted for functional outcomes of total laryngeal transplantation through PubMed/MEDLINE, Embase, Scopus, and Web of Science databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Case reports, case series, letters to the editor, reviews, and preclinical studies related to laryngeal transplantation were eligible for inclusion. Methodological quality and risk of bias were assessed via the CAMARADES checklist for preclinical studies and the JBI checklists for clinical studies.

Results: Out of n=188 identified studies, n=16 (8.5%) met the inclusion criteria. There were n=13 (81%) clinical and n=3 (19%) preclinical studies. In preclinical models, canine and minipig studies showed partial recovery: electrical stimulation restored vocal fold mobility in n=8 (40%) of canine allografts; some minipigs recovered swallowing, vocalization, and short-term survival post-transplant without immunosuppression, though all canines remained tracheostomy-dependent. Among n=18 (100%) human recipients, speech or phonation was restored fully or partially in n=12 (67%), as well as full or partial oral intake. Here, n=3 patients (17%) died within two years post-VCA, while n=4 (36%) resumed full oral intake. Voice quality was considered as satisfactory or better than pre-VCA in n=6 (55%) patients, whereas airway patency was deemed good or excellent. Nonetheless, no patient regained full vocal fold mobility. However, n=1 (5.6%) patient was able to breathe without a tracheostomy, and n=1 (5.6%) could intermittently cap their tracheostomy tube. Immunosuppressive regimens included tacrolimus (n=18, 100%), mycophenolate mofetil (n=15, 83%), corticosteroids (n=15, 83%), and anti-thymocyte globulin (n=6, 33%), with adjunctive use of leflunomide and stem cells in select cases.

Conclusion: Laryngeal transplantation shows promising results in restoring swallowing and phonation, but challenges remain for breathing without tracheostomy. The procedure remains an experimental surgery, still associated with significant morbidity and mortality, and requires lifelong immunosuppression. Future research, including long-term follow-up, larger-scale trials and interdisciplinary collaboration, is essential to further refine this procedure and evaluate its outcomes comprehensively.

Keywords: VCA; allotransplantation; functional outcomes; laryngeal transplantation; vascularized composite allografts.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

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What are the functional outcomes of total laryngeal transplantation? A systematic review of preclinical and clinical studies

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What are the functional outcomes of total laryngeal transplantation? A systematic review of preclinical and clinical studies

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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MeSH terms

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