Consensus Study Report

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This activity was supported by congressional FY 22 appropriations made to the Reconstructive Transplant Research Program under the Clinical Network Award (HT9425-23-3-0001, Yale University). Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

International Standard Book Number-13: 978-0-309-73108-9
International Standard Book Number-10: 0-309-73108-9
Digital Object Identifier: https://doi.org/10.17226/28580
Library of Congress Control Number: 2025938253

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2025. Advancing face and hand transplantation: Principles and framework for developing standardized protocols. Washington, DC: The National Academies Press. https://doi.org/10.17226/28580.

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COMMITTEE ON PRINCIPLES AND FRAMEWORK TO GUIDE THE DEVELOPMENT OF PROTOCOLS AND STANDARD OPERATING PROCEDURES FOR FACE AND HAND TRANSPLANTS

KENNETH W. KIZER (Chair), University of California, Davis

NANCY L. ASCHER, University of California, San Francisco

ARTHUR CAPLAN, NYU Grossman School of Medicine

LINDA CENDALES, Duke University Medical Center

DAVID CRANDELL, Massachusetts General Brigham Spaulding Rehabilitation; Harvard Medical School

SUSAN S. ELLENBERG, University of Pennsylvania School of Medicine

MICHELE B. GOODWIN, Georgetown University Law School

L. SCOTT LEVIN, University of Pennsylvania School of Medicine

MARIE-CHRISTINE NIZZI, Precision Psychologie

JUSTIN M. SACKS, Washington University in St. Louis School of Medicine

LAURA A. SIMINOFF, Temple University College of Public Health

JOHN E. WARE, JR., UMass Chan Medical School; John Ware Research Group

Study Staff

RUTH COOPER, Study Director

VIOLET BISHOP, Research Associate

ABIAN HAILU, Senior Program Assistant

JULIE WILTSHIRE, Senior Finance Business Partner

SHARYL J. NASS, Senior Board Director, Board on Health Care Services

CLARE STROUD, Senior Board Director, Board on Health Sciences Policy

Consultant

MICHAEL ZIERLER, Science Writer, RedOx Scientific Editing

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Reviewers

This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.

We thank the following individuals for their review of this report:

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by SARA ROSENBAUM, George Washington University, and JEFFREY KAHN, Johns Hopkins University. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.

Acknowledgments

The study committee and the Health and Medicine Division project staff take this opportunity to recognize and thank the many individuals who shared their time and expertise to support the committee’s work and to inform deliberations. The committee appreciates the Department of Defense Reconstructive Transplant Research program and Yale University, as the Coordinating Center of CONSORT, for their support.

The committee benefited greatly from discussions with individuals who participated during the committee’s open sessions. The committee would like to thank all the speakers and participants who played a role in the open sessions conducted for this study and the many others who provided valued insights, including those who submitted protocols, comments, and data for committee consideration. The open session speakers, with their affiliations at the time of their presentations to the committee, are listed in Appendix B. The committee thanks the many transplant recipients and caregivers who shared their perspectives and experiences. The committee would like to particularly thank the study’s lived experience consultants—Sheila Advento, Carmen Blandin Tarleton, William Lautzenheiser, and Carrie (Pratt) Kinan—for providing valuable input throughout the study process. Deep appreciation goes to the many staff within the National Academies who provided support at various times throughout this project. The committee and project staff are grateful to Michael Zierler for his drafting and editorial assistance to prepare this report. The committee also gives special thanks to Robert Pool and Nancy Tuvesson, copyeditors.

The committee also thanks the National Academy of Sciences W. K. Kellogg Foundation Fund for funding the consensus report’s dissemination.

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Contents

ACRONYMS AND ABBREVIATIONS

SUMMARY

PART I—BACKGROUND ON VCA

1 INTRODUCTION AND STUDY CONTEXT

Study Origin and Statement of Task

Study Context

Study Scope and Focus

Methodology and Study Approach

Report Organization and Goals

References

2 VCA BACKGROUND INFORMATION AND CONTEXT

VCA: Definition and Background

U.S. Face and Hand Transplant Centers

Select Populations and VCA

The Organ Donation System and VCA

Chapter 2 Key Findings

References

3 OVERARCHING CONSIDERATIONS INFLUENCING FACE AND HAND TRANSPLANTATION

Regulatory and Legal Considerations

Ethical Considerations

High-Quality Care Considerations

Psychosocial Considerations

Financing Considerations

Chapter 3 Key Findings

The Way Forward and Overarching Conclusions

References

PART II—THE TRANSPLANT EXPERIENCE

4 THE TRANSPLANT EXPERIENCE: THE PREOPERATIVE STAGE

Focus Area Definitions

Multidisciplinary Teams

The Pretransplant Experience

Chapter 4 Key Findings

References

5 THE TRANSPLANT EXPERIENCE: SURGICAL PROCEDURES AND CARE MANAGEMENT

Surgical Procedures

Posttransplant Care Management and Monitoring

Immunosuppression to Minimize Transplant Rejection

Monitoring and Care Management of Complications

Rehabilitation

Psychosocial Care Management

Chapter 5 Key Findings

References

6 THE TRANSPLANT EXPERIENCE: OUTCOMES

Overview of Health Outcomes

Outcomes Following Face and Hand Transplantation

Limitations in Current Outcome Measurements

Future Directions

Chapter 6 Key Findings

The Way Forward and Overarching Conclusions

References

PART III—THE FUTURE OF FACE AND HAND TRANSPLANTATION

7 FRAMEWORK FOR THE FUTURE AND DESIGNING A PRODUCTIVE AND SUSTAINABLE CLINICAL NETWORK

The Committee’s Principles, Framework, and Vision for the Future of Face and Hand Transplantation

Guidance for CONSORT

Development of Standardized Clinical Protocols and Standard Operating Procedures

Chapter 7 Key Findings

References

8 DATA MANAGEMENT AND REGISTRY DEVELOPMENT

Current Registries That Collect Face and Hand Transplant Data

Best Practices in Registry Development and Exemplars

Infrastructure and Sustainability

Specific Considerations for Patient-Reported Outcomes in Registries

Patient Data Sharing and Privacy Considerations

Involvement of International Sites

Chapter 8 Key Findings

Part III Overarching Conclusions

References

9 OVERARCHING CONCLUSIONS AND RECOMMENDATIONS

Overarching Conclusions

Whole Health Approach to Face and Hand Transplant Care at Demonstrably High-Quality Transplant Centers

Collaboration and Standardization

Systematic Approach to Continued Investigation

APPENDIXES

A Biographical Sketches of Committee Members and Staff

B Open Session Agendas

C Timeline of Previous Face and Hand Transplantations

D Relevant National Academies Studies and Historical and Ongoing VCA Work

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Boxes, Figures, and Tables

BOXES

S-1 Statement of Task

1-1 Statement of Task

1-2 Insights from Other Types of Transplants

1-3 Challenges to the Growth of Face and Hand Transplantation

1-4 Lived Experience Consultants Biographical Biosketches

2-1 Organ Procurement and Transplantation Network (OPTN) Definition of Vascularized Composite Allotransplantation (VCA)

2-2 Organ Procurement and Transplantation Network (OPTN) Body Parts Included as Vascularized Composite Allotransplantations (VCAs)

4-1 Areas of Expertise of the Multidisciplinary Team Members Involved in Face and Hand Transplantation

4-2 Common Indications, Contraindications, and Relative Contraindications for Face Transplant

4-3 Common Indications, Contraindications, and Relative Contraindications for Hand Transplant

7-1 Clinical Protocols and Standard Operating Procedures

7-2 Annotated References of Consensus Development Influences

8-1 Data Management and Registry Components of CONSORT Statement of Work

FIGURES

S-1 The whole health transplant experience

S-2 Framework for the future of face and hand transplantation

S-3 Proposed structure to guide the development of clinical protocols

1-1 RTRP clinical network objectives

2-1 Number of VCA transplants in the United States by organ, including adult and pediatric, retransplant, and multi-organ recipients

2-2 Number of face transplants performed worldwide (53 as of December 2024)

2-3 Domestic face transplants (20 total as of December 2024)

2-4 International bilateral and unilateral hand transplants (approximately 151 as of December 2024)

2-5 Domestic bilateral and unilateral hand transplants (38 total as of December 2024)

2-6 Relationship among HHS, HRSA, the OPTN, the OPTN contractors, and SRTR contractors

2-7 Total number of deceased donor VCA donations coordinated by OPOs 1998–2024

3-1 Major ethical considerations for face and hand transplantation

4-1 The whole health transplant experience

5-1 Soft-tissue and skeletal tissue defect classification system for facial transplantation

5-2 Immunosuppressive regimen model for VCA transplantation

6-1 Summary of the domain contents historically surveyed using exemplar psychometric and utility measures of HRQoL

6-2 Continuum of outcomes and measures for face and hand transplantation with measure examples

6-3 Patient-reported outcome instrument developmental process

7-1 Framework for the future of face and hand transplantation

7-2 Proposed structure to guide the development of clinical protocols

8-1 Overview of the key steps required for the development of a successful surgical registry

TABLES

2-1 U.S. Transplant Centers That Have Performed a Face and/or Hand Transplant (2019–2024)

4-1 Elements of a Comprehensive VCA Patient Education Program to Actively Engage Patient and Caregiver in Knowledge Acquisition

5-1 Preoperative Events to Optimize Procurement and Transplantation for VCA Surgery

5-2 Possible Medical Complications Following Face and Hand Transplantation

5-3 Definitions and Scoring Systems of Potential Allograft Changes in VCA

5-4 Rehabilitation Techniques for Face and Hand Transplant Recipients

6-1 Commonly Assessed Outcomes Following Face and Hand Transplantation

7-1 Key Themes to Success of Other U.S.-based Clinical Networks

7-2 Characteristics of Formal Consensus Development Methods

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Preface

Vascularized composite allotransplantation (VCA) is an evolving type of transplantation that involves the transplantation of a vascularized body part containing multiple tissue types (e.g., skin, fat, muscle, bone, nerves, and blood vessels) as a functional unit (e.g., a hand or face). VCA offers a therapeutic option to reconstruct severely disabling or disfiguring injuries or defects, recreate an anatomical appearance, and enhance quality of life. At present, VCA includes face, hand and upper limb, abdominal wall, uterus, penile, scalp, larynx, and trachea transplants.

Among the different types of VCA, face and hand transplantation have slowly but steadily evolved over the past two decades. With approximately 53 face transplant and 151 hand transplant recipients worldwide at the time of this writing,¹ these are the most developed types of VCA. Face and hand transplantation can have a profound impact on patients with severe facial injuries or upper limb loss, and they provide a viable treatment option for select patients who are unsatisfied with conventional reconstructive surgical outcomes or the use of a prosthetic. These procedures are generally considered life-enhancing instead of lifesaving.

Face and hand transplantations have achieved demonstrable surgical success and positive long-term outcomes for selected patients when performed at qualified transplant centers, as described in this report.

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¹ The number of face and hand transplants was calculated by recipient who received a transplant. Thus, a bilateral hand transplant is not counted as two transplants. However, a re-transplant is treated as a new transplant and therefore counted as an additional transplant in the total amount, despite the transplant being performed on the same recipient.

Nonetheless, there remain significant challenges that must be addressed. For example, at present, the various transplant centers that perform these procedures conduct the component parts of the transplant experience differently; treatment protocols are not standardized. Some protocol differences include patient selection processes, pretransplant assessments, education for patients and caregivers, the transplant surgery itself, immunosuppression regimens, rehabilitation, and collection of outcome performance metrics. With relatively so few patients, standardization of protocols is understandably challenging.

Among the greatest challenges facing transplantation generally, and face and hand transplantations specifically, are the many side effects of the lifelong immunosuppressive treatment required for patients to avoid or overcome rejection. The strict lifelong immunosuppression regimens can lead to diverse untoward consequences, including infections and sepsis, organ failure, and development of malignancies. However, most patients who have had these procedures and lived through these concerns and complications report that they would still go through the experience because of their improved quality of life as a result of the transplant. In addition to immunosuppression, there are many other ethical and functional considerations that pose challenges for VCA.

The complexity of the VCA experience and the myriad impacts on patients and their caregivers cannot be overstated. Consequently, shared decision making among the recipient, caregiver, and multidisciplinary clinical care team is a crucial part of the transplantation experience. With the active support of their caregiving team, it is essential that patients be fully engaged in the medical care decision-making processes so that they fully understand the risks, complications, and benefits of the procedure and are able to make a truly informed decision regarding their treatment. To achieve adherence with the long-term immunosuppression and rehabilitation necessary for VCA transplantation success, patients must always be at the center of the medical care universe.

This report provides a substantive overview of the history, challenges, and opportunities facing VCA broadly and face and hand transplantation specifically, and it provides a framework for the future evolution of face and hand transplantation. This is done with the specific goals of assisting the Clinical Organization Network for Standardization of Reconstructive Transplantation (CONSORT) develop standardized clinical protocols and standard operating procedures; provide safe and effective care for all VCA patients; and address the many challenges that may impede the maturation of face and hand transplantation. This report focuses on U.S.-based transplants and transplant centers; however international collaboration is critical for the future of face and hand transplantation. Since there are only a small number of qualified VCA transplant centers in the United States,

it is essential that all concerned stakeholders work together to address the significant challenges and opportunities detailed in this report.

The study committee that produced this report was highly dedicated and took on a difficult task with grace and determination, committing much time and energy to produce a report that it hopes will substantively support further development of VCA. The committee’s work was supported by the Department of Defense and Yale University, as the coordinating center for CONSORT, and the committee thanks these entities for their support. The committee further acknowledges and thanks the many others outside the committee who contributed to the report, including those who participated in the public information-gathering webinars, those who submitted comments through our Call for Perspectives, and the CONSORT principal investigators—Bohdan Pomahac, Vijay Gorantla, and Michael Davis. We thank the staff members from the National Academies of Sciences, Engineering, and Medicine, including Ruth Cooper, Violet Bishop, Abian Hailu and board directors Sharyl Nass and Clare Stroud, as well as all the other National Academies staff who contributed to the report. We are also very grateful for the writing and editing work of Michael Zierler. Finally, the committee deeply appreciated the involvement of our lived experience consultants. These are face and hand transplant recipients and caregivers who freely shared with the committee their complex, unique, and inspiring stories and first-hand insights. They also reviewed the report to ensure that it is patient-centered and resonated with their transplant experiences.

Kenneth W. Kizer, Chair
Committee on Principles and Framework to
Guide the Development of Protocols and Standard
Operating Procedures for Face and Hand Transplants

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Acronyms and Abbreviations

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