OPTN/SRTR 2021 Annual Data Report: Vascularized Composite Allograft

J. Andres Hernandez¹, Guiliano Testa², Hani I. Naga¹, Kaylyn B. Pogson³, Jonathan M. Miller^4,5, Sarah E. Booker⁶, Jesse Howell⁶, Kelley Poff⁶, Liza Johannesson², Ajay K. Israni^4,5,7, Jon J. Snyder^4,5,7, Linda C. Cendales¹

¹Department of Surgery, Duke University, Durham, NC

²Baylor University Medical Center, Dallas, TX

³School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC

⁴Scientific Registry of Transplant Recipients, Hennepin Healthcare Research Institute, Minneapolis, MN

⁵Department of Medicine, Hennepin Healthcare, University of Minnesota, Minneapolis, MN

⁶Organ Procurement and Transplantation Network, United Network for Organ Sharing, Richmond, VA

⁷Department of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN

Abstract

Year 2020 marked the first OPTN/SRTR Annual Data Report that included a chapter on vascularized composite allograft (VCA), which encompassed reviews of data collected between 2014 (when VCA was included in the Final Rule) and 2020. The present Annual Data Report shows that the number of VCA recipients in the United States continues to be small and trended downward in 2021. While data continue to be limited by sample size, trends continue to show a predominance in White, young/middle-aged, male recipients. Similar to the 2020 report, eight uterus and one non-uterus VCA graft failures were reported from 2014 through 2021. Critical to advancement of VCA transplantation will be the standardization of definitions, protocols, and outcome measures for the different VCA types. Like intestinal transplants, it is likely that VCA transplants will be concentrated and performed at referral transplant centers.

Keywords: Abdominal wall transplant, face transplant, multiorgan transplant, upper limb transplant, vascularized composite allograft (VCA)

1 INTRODUCTION

In 2014, vascularized composite allograft (VCA) was included within the Final Rule, which established regulatory oversight by the Organ Procurement and Transplantation Network (OPTN).¹^,² The Final Rule defined VCA transplantation as the transplant of any body part that meets the following nine criteria:

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 anatomical/structural unit
Transplanted into a human recipient as an anatomical/structural unit
Minimally manipulated (ie, processing that does not alter the original relevant characteristics of the organ relating to the organ’s 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 function or functions in the recipient as in the donor)
Not combined with another article such as a device
Susceptible to ischemia and, therefore, only stored temporarily and not cryopreserved
Susceptible to allograft rejection³

Last year, 2020, marked the first year of the OPTN/SRTR Annual Data Report including a chapter on VCA, which encompassed reviews of data collected between 2014 (when VCA was included in the Final Rule) and 2020.⁴ To provide context, this year, the report will also include data beginning in 2014 with a focus on the year 2021. Due to the small number of recipients, subsequent reports will aim to provide a comparison to the previous year to describe and analyze trends within the VCA community. Detailed information on VCA candidates, donors, and recipients, as well as VCA access and patient outcomes, in the United States from July 2014 through 2021 is presented below.

2 UTERUS TRANSPLANT

2.1 Candidates

Ten candidates were on the waiting list for uterus transplant in 2021 (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).

2.2 Transplants

As of December 2021, 33 uterus transplants were performed (Figure VCA 5). Most uterus transplants were performed in White (29 of 33 recipients; Figure VCA 7) women younger than 35 years (28 of 33 recipients; Figure VCA 6). Uterus transplant recipients were predominantly blood types A or O (29 of 33 recipients; Figure VCA 8). Primary diagnosis of absolute uterine factor infertility due to congenital absence of the uterus was present in 25 of 33 recipients (Figure VCA 9).

2.3 Donors

Unlike transplants for other VCA organs that use only deceased donor organs, living donor uterus transplants are performed: 64% of uterus transplants (21/33) since 2016 used living donors (Figure VCA 10). All deceased donor uterus transplants were performed with donors younger than 50 years, with most using donors aged 18-34 years. All but one of the living donors were younger than 50 years (Figure VCA 11).

2.4 Posttransplant Outcomes

Unlike other organ transplants, uterus grafts are always removed after the recipient has finished having children. Data reported to the OPTN show 21 functioning grafts and 8 uterus grafts failed (24% of 33 transplants; Figure VCA 12). However, uterus transplantation is a small and growing field, and the authors are aware of 17 uterus grafts that have, in fact, been removed after successful child delivery. The essential outcome variable for a uterus transplant is a live birth. While number of births is not yet captured in the data, as of December 2021, the authors are aware of 21 children who have been born to 19 uterus transplant recipients.

2.5 Access

Uterus transplants through 2021 were performed at centers in three states: Ohio, Pennsylvania, and Texas. Of these, most transplants have been performed in Texas (67%, 22/33; Table VCA 1).

3 VCA TRANSPLANTS OTHER THAN UTERUS

3.1 Candidates

The total number of candidates listed for non-uterus VCA has remained stable since 2014 when the OPTN VCA waiting list was established, with 18 total candidates ever waiting in 2021 (Figure VCA 13). Since 2014, candidate listings by organ type show that the most common has been upper limb (43%, 23/53) and the least common has been “other/multiple” (13%, 7/53). Annual data are difficult to evaluate due to sample size; however, at the end of 2021, seven patients were waiting for abdominal wall transplant, three were waiting for face transplant, six were waiting for upper limb transplant, and two were waiting for other/multiple transplant (Figures VCA 13 and 14).

Similar to last year’s report, most non-uterus VCA candidates listed since 2014 were aged 18-34 years (32%, 17/53), 35-49 years (26%, 14/53), and 50-64 years (30%, 16/53) (Figure VCA 15). By race and ethnicity, most non-uterus VCA transplant candidates identified as White (74%, 39/53), followed by Hispanic (13%, 7/53), Black (11%, 6/53), and other (2%, 1/53) (Figure VCA 16). Since 2014, non-uterus VCA transplant candidates have predominantly been male (70%, 37/53) (Figure VCA 17) with blood type O (45%, 24/53), followed by type A (34%, 18/53), type B (17%, 9/53), and type AB (4%, 2/53) (Figure VCA 18). In addition, when evaluating median days to transplant by organ type since 2014, the longest time to transplant was scalp (355 days). Median days to transplant for face, penis, other/multiple, upper limb, and abdominal wall were 342 days, 262 days, 238 days, 186 days, and 125 days, respectively (Figure VCA 19).

3.2 Donors

With respect to age, most donors from 2014 through 2021 were within the 18- to 34-year age group (52%, 16/31). Data for the remaining age groups are as follows: 13% (4/31) were younger than 18 years, 32% (10/31) were aged 35-49 years, and 3% (1/31) were aged 50-64 years (Figure VCA 27).

3.3 Recipients

Since July 3, 2014, of the 53 total non-uterus VCA transplant candidates listed, 31 (58%) have undergone transplants. While it continues to be difficult to evaluate data trends due to sample size limitations, no substantial change has been seen in VCA transplants performed annually from 2014 through 2021 (Figure VCA 20). The most commonly transplanted non-uterus VCA was upper limb (48%, 15/31), followed by face (35%, 11/31), other (including penis and scalp; 10%, 3/31), and abdominal wall (6%, 2/31) (Figures VCA 20 and 21).

Demographic data for patients who underwent non-uterus VCA transplant in 2014 through 2021 are as follows. The three most common causes of need for VCA transplant were trauma (45%, 14/31), infection (26%, 8/31), and burn/explosion (6%, 2/31). However, 10% (3/31) of data was missing (Figure VCA 26), which was similar to our previous (2020) report. The most common age group among non-uterus VCA transplant recipients was 18-34 years (39%, 12/31), followed by 50-64 years (29%, 9/31), 35-49 years (19%, 6/31), 65 years or older (10%, 3/31), and younger than 18 years (3%, 1/31) (Figure VCA 22). Due to small numbers of non-White recipients, race within the non-uterus VCA transplant recipient group has continued to be presented differently from that in the listed non-uterus VCA candidate group; for recipients, race is stratified as White and non-White. The proportions of White and non-White non-uterus VCA transplant recipients were 81% (25/31) and 19% (6/31), respectively (Figure VCA 23). Non-uterus VCA transplant recipients were mostly male (74%, 23/31) (Figure VCA 24) with blood type O (48%, 15/31), followed by type A (29%, 9/31) and type B (23%, 7/31). No transplants were performed in patients with type AB blood (Figure VCA 25).

3.4 Access and Outcomes

Nineteen centers in 11 US states have performed non-uterus VCA transplants since July 2014 (Table VCA 3). In terms of the number of centers performing VCA transplants by organ, upper limb is the most common (nine centers), followed by face (five centers), abdominal wall (two centers), penis (two centers), and scalp (one center) (Figure VCA 28). Compared with last year’s report, centers performing upper limb and face VCA transplants since 2014 have slightly increased (8 to 9 and 4 to 5, respectively).⁴

Regarding patient outcomes for non-uterus VCA transplant, end points were broken into two groups per organ type: “functioning graft” and “failed graft.” In the period being discussed (2014-2021), only 7% of upper limb VCAs (1/15) failed, and there was a 100% functioning graft rate in abdominal wall, face, penis, and scalp VCA transplants (Table VCA 2).

4 OBSERVATIONS

Vascularized composite allotransplantation continues to evolve with advances in techniques, immunomodulation, and patient selection. Nonetheless, the number of VCA recipients within the United States continues to be small and trended downward in 2021. Although it is clear that the inclusion of VCA transplant within the Final Rule in 2014 was a milestone for the field, several factors may be contributing to this trend in 2021, including lack of funding and VCA programs’ access to resources necessary to sustain programs and possibly continued impact of the COVID-19 pandemic. Other challenges that the VCA community faces include unstandardized definitions, non-validated VCA outcome-specific tools, chronic rejection, and missingness of data entries submitted to the OPTN database. To address some of these challenges, VCA will be integrated into the OPTN Computer System (UNet) in 2023, and will include implementation of several approved modifications to policy/data collection, including updates to the definition of VCA graft failure. Like intestinal transplants, it is likely that VCA transplants will be concentrated and performed at referral transplant centers.

REFERENCES

McDiarmid SV, Levin LS, Luskin RS. Vascularized composite tissue allografts (VCA): the policy side. Curr Transplant Rep. 2016;3:50-56. doi:10.1007/s40472-016-0094-9

Cherikh WS, Cendales LC, Wholley CL, 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(3):865-875. doi:10.1111/ajt.15062

Wholley CL. List Covered Body Parts Pertaining to VCA. OPTN/UNOS Vascularized Composite Allograft (VCA) Transplantation Committee. 2016. Accessed November 7, 2022. https://optn.transplant.hrsa.gov/media/1864/vca_briefingpaper_201606.pdf.

Hernandez JA, Miller J, Oleck NC, et al. OPTN/SRTR 2020 Annual Data Report: VCA. Am J Transplant. 2022;22(suppl2):623-647. doi:10.1111/ajt.16980

This publication was produced for the U.S. Department of Health and Human Services (HHS), Health Resources and Services Administration (HRSA), by Hennepin Healthcare Research Institute (HHRI) and the United Network for Organ Sharing (UNOS) under contracts HHSH75R60220C00011 and HHSH250201900001C, respectively.

This publication lists nonfederal resources in order to provide additional information to consumers. The views and content in these resources have not been formally approved by HHS or HRSA. Neither HHS nor HRSA endorses the products or services of the listed resources.

The OPTN/SRTR 2021 Annual Data Report is not copyrighted. Readers are free to duplicate and use all or part of the information contained in this publication. Data are not copyrighted and may be used without permission if appropriate citation information is provided.

Pursuant to 42 U.S.C. 1320b-10, this publication may not be reproduced, reprinted, or redistributed for a fee without specific written authorization from HHS.

Suggested Citations:
Full citation: Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2021 Annual Data Report. U.S. Department of Health and Human Services, Health Resources and Services Administration; 2023. Accessed [insert date]. http://srtr.transplant.hrsa.gov/annual_reports/Default.aspx
Abbreviated citation: OPTN/SRTR 2021 Annual Data Report. HHS/HRSA; 2023. Accessed [insert date]. http://srtr.transplant.hrsa.gov/annual_reports/Default.aspx

Publications based on data in this report or supplied on request must include a citation and the following statement: The data and analyses reported in the OPTN/SRTR 2021 Annual Data Report have been supplied by the United Network for Organ Sharing and Hennepin Healthcare Research Institute under contract with HHS/HRSA. The authors alone are responsible for reporting and interpreting these data; the views expressed herein are those of the authors and not necessarily those of the U.S. government.

This report is available at https://srtr.transplant.hrsa.gov. Individual chapters may be downloaded.

List of Figures

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 2016
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 non-uterus 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 transplant hospitals performing VCA transplants by non-uterus organ since 2014

List of Tables

Table VCA 1: Number of uterus transplants by state where transplant hospital is located
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 hospital is located

**Number of prevalent uterus candidates.** Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time during the year.

Figure VCA 1: Number of prevalent uterus candidates. Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time during the year.

**Number of uterus candidates by age since 2016.** Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

Figure VCA 2: Number of uterus candidates by age since 2016. Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

**Number of uterus candidates by race since 2016.** Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

Figure VCA 3: Number of uterus candidates by race since 2016. Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

**Number of uterus candidates by blood type since 2016.** Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

Figure VCA 4: Number of uterus candidates by blood type since 2016. Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

Figure VCA 5: Number of uterus transplants. All uterus transplant recipients, including retransplant, and multiorgan recipients.

**Number of uterus transplants by age since 2016.** All uterus transplant recipients, including retransplant, and multiorgan recipients.

Figure VCA 6: Number of uterus transplants by age since 2016. All uterus transplant recipients, including retransplant, and multiorgan recipients.

$**Number of uterus transplants by race since 2016.** All uterus transplant recipients, including retransplant, and multiorgan recipients.$

Figure VCA 7: Number of uterus transplants by race since 2016. All uterus transplant recipients, including retransplant, and multiorgan recipients.

**Number of uterus transplants by blood type since 2016.** All uterus transplant recipients, including retransplant and multiorgan recipients.

Figure VCA 8: Number of uterus transplants by blood type since 2016. All uterus transplant recipients, including retransplant and multiorgan recipients.

**Number of uterus transplants by diagnosis since 2016.** All uterus transplant recipients, including retransplant, and multiorgan recipients.

Figure VCA 9: Number of uterus transplants by diagnosis since 2016. All uterus transplant recipients, including retransplant, and multiorgan recipients.

**Number of uterus transplants by donor type since 2016.** All uterus transplant recipients, including retransplant, and multiorgan recipients.

Figure VCA 10: Number of uterus transplants by donor type since 2016. All uterus transplant recipients, including retransplant, and multiorgan recipients.

**Number of uterus transplants by donor age since 2016.** All uterus transplant recipients, including retransplant, and multiorgan recipients.

Figure VCA 11: Number of uterus transplants by donor age since 2016. All uterus transplant recipients, including retransplant, and multiorgan recipients.

$**Posttransplant outcome counts among uterus transplant recipients since 2016.** All uterus transplant recipients, including retransplant, and multiorgan recipients.$

Figure VCA 12: Posttransplant outcome counts among uterus transplant recipients since 2016. All uterus transplant recipients, including retransplant, and multiorgan recipients.

**Number of prevalent non-uterus VCA candidates by organ.** Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time during the year.

Figure VCA 13: Number of prevalent non-uterus VCA candidates by organ. Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time during the year.

**Number of non-uterus VCA candidates by organ type since 2014.** Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

Figure VCA 14: Number of non-uterus VCA candidates by organ type since 2014. Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

**Number of non-uterus VCA candidates by age since 2014.** Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

Figure VCA 15: Number of non-uterus VCA candidates by age since 2014. Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

**Number of non-uterus VCA candidates by race/ethnicity since 2014.** Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

Figure VCA 16: Number of non-uterus VCA candidates by race/ethnicity since 2014. Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

**Number of non-uterus VCA candidates by sex since 2014.** Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

Figure VCA 17: Number of non-uterus VCA candidates by sex since 2014. Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

**Number of non-uterus VCA candidates by blood type since 2014.** Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

Figure VCA 18: Number of non-uterus VCA candidates by blood type since 2014. Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time.

**Median days to transplant among non-uterus VCA candidates by organ since 2014.** Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time. Organs with no visible bar in the graph have a median days to transplant of 0, meaning that more than 50% of candidates are added to the list on the same day that they are transplanted or do not have a recorded listing date, in which case their listing date is assumed to be their transplant date.

Figure VCA 19: Median days to transplant among non-uterus VCA candidates by organ since 2014. Candidates listed at multiple centers are counted once per listing. Includes active and inactive candidates on the list any time. Organs with no visible bar in the graph have a median days to transplant of 0, meaning that more than 50% of candidates are added to the list on the same day that they are transplanted or do not have a recorded listing date, in which case their listing date is assumed to be their transplant date.

**Number of non-uterus VCA transplants by organ.** Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients.

Figure VCA 20: Number of non-uterus VCA transplants by organ. Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients.

**Number of non-uterus VCA transplants by organ type since 2014.** Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients. 'Other/Multiple' category includes penis, scalp and abdominal wall transplants.

Figure VCA 21: Number of non-uterus VCA transplants by organ type since 2014. Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients. ‘Other/Multiple’ category includes penis, scalp and abdominal wall transplants.

**Number of non-uterus VCA transplants by age since 2014.** Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients.

Figure VCA 22: Number of non-uterus VCA transplants by age since 2014. Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients.

**Number of non-uterus VCA transplants by race since 2014.** Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients.

Figure VCA 23: Number of non-uterus VCA transplants by race since 2014. Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients.

**Number of non-uterus VCA transplants by sex since 2014.** Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients.

Figure VCA 24: Number of non-uterus VCA transplants by sex since 2014. Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients.

**Number of non-uterus VCA transplants by blood type since 2014.** Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients.

Figure VCA 25: Number of non-uterus VCA transplants by blood type since 2014. Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients.

**Number of non-uterus VCA transplants by diagnosis since 2014.** Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients.

Figure VCA 26: Number of non-uterus VCA transplants by diagnosis since 2014. Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients.

**Number of non-uterus VCA transplants by donor age since 2014.** Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients.

Figure VCA 27: Number of non-uterus VCA transplants by donor age since 2014. Non-uterus VCA transplant recipients, including adult and pediatric, retransplant, and multiorgan recipients.

**Number of transplant hospitals performing VCA transplants by non-uterus organ since 2014.** All unique transplant hospitals performing non-uterus VCA transplants by organ type

Figure VCA 28: Number of transplant hospitals performing VCA transplants by non-uterus organ since 2014. All unique transplant hospitals performing non-uterus VCA transplants by organ type