OPTN/SRTR 2020 Annual Data Report: VCA

Abstract

The first vascularized composite allograft (VCA) transplant in the United States was performed in 1998 in a 40-year-old man who received a laryngeal transplant after experiencing severe trauma to the throat 20 years before. The following VCA was a hand transplant in 1999 in a 37-year-old man who lost his left hand 13 years before. Since then, the field of VCA transplantation has made significant strides. On July 3, 2014, the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) oversight of VCA procurement and transplant in the United States went into effect. In the last decade, the number of candidates listed for and transplanted with VCA has increased. While patient demographic data, whether listed candidates or patients undergoing VCA transplant, is limited by sample size, the trend is a predominance toward a young/middle-aged, White population. Overall outcomes data have been promising, with the vast majority of VCA transplants resulting in functioning grafts.

Introduction

Vascularized composite allograft (VCA) transplantation has grown as a field over the last 20 years since the first transplants in 1999.^1,2 This growth in academic interest and surgical implementation has a rich history derived from lessons and advances in microsurgery and transplant. In 2008, the United States Department of Health and Human Services asked for oversight of VCA transplant, beginning with a definition and inclusion as an organ in the Final Rule.³ In 2014, VCA was defined in the Final Rule, which established ongoing Organ Procurement and Transplantation Network (OPTN) oversight and gave access to solid-organ procurement and transplant guidelines.^4,5 The definition of VCA transplant is the transplant of any body part which meets all of the following criteria:⁶

• Is vascularized and requires blood flow by surgical connection of blood vessels to function after transplant

• Contains multiple tissue types

• Recovered from a human donor as an anatomic/structural unit

• Surgically implanted in a human recipient as an anatomic/structural unit

• Minimally manipulated (ie, processing that does not alter the original relevant characteristics of the organ relating to its utility for reconstruction, repair, or replacement)

• For homologous use (the replacement or supplementation of a recipient’s organ with an organ that performs the same basic functions in the recipient as in the donor)

• Not combined with another article such as a device

• Susceptible to ischemia and, therefore, stored only temporarily and without cryopreservation

• Susceptible to allograft rejection

Interest in VCA transplant has increased as immunosuppressive regimens and innovative procedures have been developed. Detailed information on VCA candidates, donors, and recipients, as well as VCA access and patient outcomes, is presented below. Mandatory data collection began in 2015, and was retroactive to July 3, 2014 when VCA was included in the Final Rule; therefore trends presented here are from transplants performed after July 3, 2014, when data reporting is relatively complete. Since 2016, uterus transplant has become the most common VCA transplant type and data on uterus transplants are presented separately before data on VCA transplants other than uterus.

Uterus Transplants

Candidates

Seven candidates were on the waiting list for uterus transplant at some point in 2016. This number rose to 25 candidates on the waiting list at some point in 2019, before reverting to 8 in 2020, possibly due to the COVID-19 pandemic (Figure VCA 1). Most uterus transplant candidates have been younger than 35 years (Figure VCA 2) and White (Figure VCA 3), with blood types A or O (Figure VCA 4). The median days to transplant for waitlisted uterus candidates was 17 days among all candidates, a short time as many uterus candidates receive organs from living donors. Among uterus candidates waiting for deceased donor transplant, the median time to transplant was 136 days.

Transplants

As of December 31, 2020, 31 uterus transplants have been performed. The number of uterus transplants rose from 6 in 2016 to 12 in 2019, before reverting to 2 in 2020 (Figure VCA 5). Most uterus transplants have been performed in White (Figure VCA 7) women younger than 35 years (Figure VCA 6). Uterus transplant recipients have predominantly had blood types A or O (Figure VCA 8) with a primary diagnosis of absolute uterine factor infertility due to the congenital absence of the uterus (Figure VCA 9).

Donors

Unlike other VCA organs that use only deceased donor organs, living donor uterus transplants are performed: 61% of uterus transplants (19/31) since 2016 used living donors (Figure VCA 10). Almost all uterus transplants were performed with donors younger than 50 years old, with equal numbers done using 18 to 34-year old donors and using 35 to 49-year old donors (Figure VCA 11).

Posttransplant Outcomes

Unlike other organ transplants, uterus grafts are always removed after the recipient has finished having children. Of the 31 uterus transplants performed since 2016, 19 grafts are still functioning. Three recipients have had their graft removed, which is typically done after the recipient is finished having children. Uterus grafts failed in 8 (26%) of transplants (Figure VCA 12). The essential outcome variable for a uterus transplant is a live birth. As of November, 2021, 21 children have been born to 19 uterus transplant recipients.

Access

Uterus transplants are performed at centers in 3 states: Ohio, Pennsylvania, and Texas. Of these, most transplants have been performed in Texas (65%,20/31) (Table VCA 1).

VCA Transplants Other than Uterus

Candidates

Since July 3, 2014, 49 candidates have been listed for non-uterus VCA (Figure VCA 14). The most common organ listing was for an upper limb (47%, 23/49); 11 of the 23 upper limb candidates were listed for bilateral upper limb transplant. Face, abdominal wall, and other VCA types, including penis, face/scalp and face/bilateral upper limb, were relatively less common. The number of candidates waiting for a VCA transplant at any time during a year has been relatively stable at 14 to 20 patients from 2015 to 2020 (Figure VCA 13). During 2020, 4 patients were waiting for abdominal wall transplant, 5 were listed for face transplant, 6 were listed for upper limb transplant, and 2 were listed for other/multiple transplant (Figure VCA 13).

Most non-uterus VCA candidates listed were within the 18- to 34-year (35%, 17/49), 35- to 49-year (27%, 13/49) and 50- to 64-year (27%, 13/49) age groups (Figure VCA 15). Most candidates were White (73%, 36/49), with Hispanic, Black, and other race/ethnicities representing 12% (6/49), 12% (6/49), and 2% (1/49), respectively (Figure VCA 16). Non-uterus VCA transplant candidates since 2014 have mostly been men (71%, 35/49) (Figure VCA 17), predominantly with blood type O (45%, 22/49), followed by A (35%, 17/49), B (16%, 8/49), and AB (4%, 2/49), respectively (Figure VCA 18). Since a national waiting list for VCA transplants was created in 2014, the median time to transplant has been longest for face transplant (378 days) and shortest for abdominal wall transplant (125 days) (Figure VCA 19).

Transplants

Since July 3, 2014, of the 49 listed non-uterus VCA transplant candidates, 25 (51%) transplants have been performed in 24 candidates, including one candidate that received transplants of face and bilateral upper limb. The number of non-uterus VCA transplants performed per year ranged from 2 to 7 from 2015 to 2020 (Figure VCA 20). The most common transplanted VCA was upper limb (52%, 13/25), followed by face (32%, 8/25), abdominal wall (8%, 2/25), and penis (8%, 2/25) (Figure VCA 21).

The most common primary diagnoses for VCA transplant were trauma (48%, 12/25) and infection (28%, 7/25) (Figure VCA 26). The most common age group among VCA transplant recipients was 18 to 34 years (40%, 10/25), followed by 50 to 64 years (28%, 7/25), 35 to 49 years (16%, 4/25), 65 years and older (12%, 3/25), and younger than 18 years (4%, 1/25) (Figure VCA 22). Eighty percent of non-uterus VCA transplant recipients (20/25) were White, and 20% (5/25) were other races (Figure VCA 23). Non-uterus VCA transplant recipients were mostly men (76%, 19/25) (Figure VCA 24) with blood type O (44%, 11/25), followed by A (32%, 8/25), and B (24%, 6/25) (Figure VCA 25).

Donors

Through 2020, all non-uterus VCA transplants have received organs from deceased donors. Most donors were 18 to 34 years (44%, 11/25). Sixteen percent (4/25) of donors were younger than 18 years, 36% (9/25) were 35 to 49 years, and 4% (1/25) were 50 to 64 years (Figure VCA 27).

Posttransplant Outcomes

Of abdominal wall, face, and penis transplants performed since July 3, 2014, all have resulted in a functioning graft. Of upper limb transplants, 92% (12/13) resulted in a functioning graft, with 1 graft failure (8%) (Table VCA 2).

For upper limb transplant, 3 functional metrics are included in the OPTN database; quantitative evaluation of upper extremity function; Disability of Arm, Shoulder and Hand (DASH) score; and Semmes-Weinstein test, which evaluates sensory recovery.^7-9 Of the data reported to the OPTN 5 years after July 3, 2014, patients showed improvement in the quantitative function scores, the DASH scores, and the sensory recovery test after hand transplant; among face transplant recipients, 50% had their tracheostomy decannulated and regained their sense of smell, 33% had their feeding tube removed, and the same percentage regained the ability protect their cornea through eye closure.¹⁰

Access

VCA transplant is performed in a small number of programs in the United States, with 10 states having performed at least 1 such transplant since July 3, 2014 (Table VCA 3). When considering the number of centers performing each VCA type since 2014, upper limb is the most common (8 centers), followed by face (4), abdominal wall (2), and penis (2) (Figure VCA 28).

Discussion

At this stage in the field of VCA transplant, unmet needs include standardized outcome measures and definitions of success. For uterus transplant, standard outcome measures¹¹ have been proposed, including:

• A technically successful transplant that results in a viable graft at postoperative day 30

• First demonstration of graft function with resumption of menstrual bleeding in response to the hormonal cyclicity of the recipient (or withdrawal bleeding in response to hormonal stimulation and removal)

• Achievement of pregnancy after embryo transfer (defined as positive fetal heart rate on ultrasound)

• Maintenance of pregnancy to delivery

• Successful delivery of 1 or more live-born children

• Cessation of immunosuppression and removal of the graft (transplant hysterectomy)

• Long-term follow-up of recipient and offspring outcomes

A proposed definition of graft success for upper limb transplant includes attaining at least 2 of the following parameters: positive recipient perception of function, ability to perform basic activities of daily living, sensory recovery to at least protective sensation, return to work, and/or the ability to make composite finger flexion and extension with donor hands. A proposed definition of incomplete graft loss is amputation of segments of the transplanted limb (eg, digits), and a proposed definition of complete graft loss is amputation of the allograft. The time of the specific assessment needs to be factored into the metric to correct for the level of the upper limb transplant (eg, above the elbow vs distal forearm transplants). As such, a proposed time for graft success reporting is 1 year for transplant at the distal forearm, 2 years for transplant at the proximal forearm, and 3 years for transplant above the elbow.¹²

References

1. Strome M, Stein J, Esclamado R, Hicks D, Lorenz RR, Braun W, et al. Laryngeal transplantation and 40-month follow-up. N Engl J Med 2001;344:1676-1679

2. Jones JW, Gruber SA, Barker JH, Breidenbach WC. Successful hand transplantation. One-year follow-up. Louisville Hand Transplant Team. N Engl J Med 2000 Aug 17;343(7):468-73 DOI: 10.1056/NEJM200008173430704

3. Department of Health and Human Services. Organ Procurement and Transplantation Network; Final Rule. Federal Register 2013, 78(128), 40033-40042.

4. McDiarmid SV, Levin LS, Luskin RS. Vascularized composite tissue allografts (VCA): The Policy Side. Curr Transplant Reports. 2016;3:50-56.

5. Cherikh WS, Cendales L, Wholley C, et al. Vascularized composite allotransplantation in the United States: A descriptive analysis of the Organ Procurement and Transplantation Network Data. Am J Transplant. 2019;19:865875.

6. Wholley, CL. List covered body parts pertaining to VCA. OPTN/UNOS Vascularized Composite Allograft (VCA) Transplantation Committee https://optn.transplant.hrsa.gov/media/1864/vca_briefingpaper_201606.pdf.

7. Carroll D. A quantitative test of upper extremity function. J Chronic Dis. 1965;18:479-491.

8. Amadio PC. Outcome assessment in hand surgery and hand therapy: An update. J Hand Therapy. 2001;14(2):63-67.

9. Hudak P, Amadio PC, Bombardier C. Development of an upper extremity outcome measure: the DASH (Disabilities of the Arm, Shoulder, and Head). Am J Ind Med. 1996;29:602-608.

10. Lewis H, Cendales L. Vascularized composite allotransplantation in the United States: A retrospective analysis of the Organ Procurement and Transplant Network data after 5 years of the Final Rule. Am J Transplant. 2021;21:291-296.DOI: 10.1111/ajt.16086

11. Johannsson L, Testa G, Flyckt R, et al. Guidelines for standardized nomenclature and reporting in uterus transplantation: An opinion from the United States Uterus Transplant Consortium. Am J Transplant. 2020;20(12):3319-3325.

12. Hein R, Ruch D, Klifto C, et al. Hand transplantation in the United States: A review of the Organ Procurement and Transplantation Network/United Network for Organ Sharing Database. Am J Transplant. 2020;20:1417-1423. DOI: 10.1111/ajt.15704

Figure List

Uter

Figure VCA 1. Number of prevalent uterus candidates
Figure VCA 2. Number of uterus candidates by age since 2016
Figure VCA 3. Number of uterus candidates by race since 2016
Figure VCA 4. Number of uterus candidates by blood type since 2016
Figure VCA 5. Number of uterus transplants
Figure VCA 6. Number of uterus transplants by age since 2016
Figure VCA 7. Number of uterus transplants by race since 2016
Figure VCA 8. Number of uterus transplants by blood type since 2016
Figure VCA 9. Number of uterus transplants by diagnosis since 2016
Figure VCA 10. Number of uterus transplants by donor type since 2016
Figure VCA 11. Number of uterus transplants by donor age since 2016
Figure VCA 12. Posttransplant outcome counts among uterus transplant recipients since 2009

Nonuter

Figure VCA 13. Number of prevalent non-uterus VCA candidates by organ
Figure VCA 14. Number of non-uterus VCA candidates by organ type since 2014
Figure VCA 15. Number of non-uterus VCA candidates by age since 2014
Figure VCA 16. Number of non-uterus VCA candidates by race/ethnicity since 2014
Figure VCA 17. Number of VCA candidates by sex since 2014
Figure VCA 18. Number of non-uterus VCA candidates by blood type since 2014
Figure VCA 19. Median days to transplant among non-uterus VCA candidates by organ since 2014
Figure VCA 20. Number of non-uterus VCA transplants by organ
Figure VCA 21. Number of non-uterus VCA transplants by organ type since 2014
Figure VCA 22. Number of non-uterus VCA transplants by age since 2014
Figure VCA 23. Number of non-uterus VCA transplants by race since 2014
Figure VCA 24. Number of non-uterus VCA transplants by sex since 2014
Figure VCA 25. Number of non-uterus VCA transplants by blood type since 2014
Figure VCA 26. Number of non-uterus VCA transplants by diagnosis since 2014
Figure VCA 27. Number of non-uterus VCA transplants by donor age since 2014
Figure VCA 28. Number of centers performing VCA transplants by non-uterus organ since 2014

Table List

Uter

Table VCA 1. Number of uterus transplants by state where transplant center is located

Nonuter

Table VCA 2. Posttransplant outcome counts by non-uterus VCA organ type since 2014
Table VCA 3. Number of non-uterus VCA transplants by state where transplant center is located

Table VCA 1. Number of uterus transplants by state where transplant center is located
All uterus transplant recipients, including retransplant, and multi-organ recipients.

State	Transplant Count
Ohio	8
Pennsylvania	3
Texas	20

Table VCA 2. Posttransplant outcome counts by non-uterus VCA organ type since 2014
Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multi-organ recipients.

Organ	Functioning graft	Graft failed
Abdominal Wall	2	0
Face	8	0
Penis	2	0
Upper Limb	12	1

Table VCA 3. Number of non-uterus VCA transplants by state where transplant center is located
Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multi-organ recipients.

State	Transplant Count
California	1
Florida	1
Kentucky	2
Massachusetts	5
Maryland	3
Minnesota	1
North Carolina	4
New York	4
Ohio	1
Pennsylvania	3