Effect of ABO-Incompatible Listing on Infant Heart Transplant Waitlist Outcomes: Analysis of the United Network for Organ Sharing (UNOS) Database

doi:10.1016/j.healun.2009.06.024

The Journal of Heart and Lung Transplantation

Volume 28, Issue 12, December 2009, Pages 1254-1260

https://doi.org/10.1016/j.healun.2009.06.024 Get rights and content

Background

Midterm heart transplant outcomes of ABO-incompatible (ABO-I) organ use in infants are favorable. ABO-I transplantation has resulted in reduced waitlist mortality in some countries. This study assessed the effect of an ABO-I listing strategy on pre-transplant outcomes in the United States.

Methods

The Organ Procurement and Transplantation Network (OPTN)/United Network of Organ Sharing (UNOS) database was used to identify infants aged younger than 1 year listed as status 1 for heart transplantation between January 1, 2001, and May 20, 2008. The cohort was divided into 2 groups: eligible for ABO-compatible (ABO-C) transplant and eligible for ABO-I transplant. Baseline characteristics, waitlist times, and outcomes were compared in univariate analysis. Competing risks analysis evaluated differences in time to transplant in the presence of other outcomes.

Results

Of 1,029 infants listed for transplant, 277 (27%) were listed for an ABO-I transplant. Overall, 92% of transplant recipients received an ABO-C organ regardless of listing type. Among recipients eligible for ABO-I, only 27% received an ABO-I organ. The percentage that underwent transplant in each group did not differ. Although infants listed for an ABO-I organ had a shorter wait time for transplant, waitlist mortality was similar.

Conclusions

Despite the intended merits of ABO-I heart transplantation, ABO-I listing and organ acceptance have not yielded lower waitlist mortality in the United States under the current UNOS allocation algorithm. Consideration should be given to altering the allocation system to one that gives less preference toward blood group compatibility in hopes of improving organ use and reducing waitlist mortality.

Section snippets

Patient Population

After administrative review and approval by our institutional research ethics board, we retrospectively reviewed de-identified patient data extracted from the Organ Procurement and Transplantation Network (OPTN)/UNOS research database. We identified all infants aged younger than 12 months listed for primary heart transplantation between January 1, 2001, and May 20, 2008. Medical urgency as defined by UNOS includes status 1A (highest clinical acuity), 1B, and 2. Only patients designated at

Patient Demographics

As of May 20, 2008, 1,029 infants aged younger than 12 months were listed to undergo heart transplantation, and 277 (27%) were listed as eligible to receive an ABO-I organ. The percentage of infants during the study period listed as eligible to accept an ABO-I organ increased over time from 5.8% (9 of 154) in 2001 to 43.9% (65 of 148) in 2007. Baseline patient characteristics at the time of listing differed between groups. Infants listed as eligible for an ABO-I transplant were smaller by

Discussion

ABO-I heart transplantation for infants without established isohemagglutinin production is increasingly performed worldwide with favorable post-transplant outcomes.7, 13, 14 These favorable results led to the acceptance of ABO-I organ transplantation in 2001 by the UNOS, which governs transplantation in the United States. Our study shows that although the number of infants listed as eligible for ABO-I transplant in the United States has steadily increased, such that approximately half of all

Disclosure Statement

This work was supported in part by Health Resources and Services Administration contracts 231-00-0115 and 234-2005-370011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

None of the authors has a financial relationship with a commercial entity that has an interest in the

References (15)

S. Horslen et al.
Pediatric transplantation in the United States, 1996–2005
Am J Translant
(2007)
N.D. Patel et al.
ABO-incompatible heart transplantation in infants: analysis of the United Network for Organ Sharing Database
J Heart Lung Transplant
(2008)
L.J. West et al.
Impact on outcomes after listing and transplantation, of a strategy to accept ABO blood group-incompatible donor hearts for neonates and infants
J Thorac Cardiovasc Surg
(2006)
S.L. Roche et al.
Multicenter experience of ABO-incompatible pediatric cardiac transplantation
Am J Transplant
(2008)
S.M. Pollock-BarZiv et al.
Competing outcomes after neonatal and infant wait-listing for heart transplantation
J Heart Lung Transplant
(2007)
A.I. Dipchand et al.
ABO-incompatible paediatric heart transplantation: the first 10 years
J Heart Lung Transplant
(2007)
D.G. Renlund et al.
New UNOS rules: historical background and implications for transplantation management
J Heart Lung Transplant
(1999)

There are more references available in the full text version of this article.

Cited by (35)

Clinical outcomes of children receiving ABO-incompatible versus ABO-compatible heart transplantation: a multicentre cohort study
2021, The Lancet Child and Adolescent Health
ABO-incompatible heart transplantation increases donor availability in young children and is evolving into standard of care in children younger than 2 years. Previous smaller studies suggest similar outcomes to ABO-compatible heart transplantation, but persisting alterations of the immune system in ABO-incompatible recipients might increase the risk of some infections or benefit the graft owing to reduced HLA reactivity. We aimed to assess long-term outcomes in young children after they received ABO-incompatible or ABO-compatible heart transplantation.
In this multicentre, prospective cohort study, we analysed data from the Pediatric Heart Transplant Society registry to compare children who received ABO-incompatible or ABO-compatible heart transplantation before age 2 years between Jan 1, 1999, and June 30, 2018. Given significantly different clinical demographics between the two groups, we also matched each ABO-incompatible recipient to two ABO-compatible recipients using propensity score matching. We assessed patient and graft survival, coronary allograft vasculopathy, malignancy, acute rejection (any episode resulting in augmentation of immunosuppression), and infections (requiring intravenous antibiotic or antiviral therapy or life-threatening infections treated with oral therapy).
We included 2206 children who received a heart transplant before age 2 years, with 11 332·6 patient-years of cumulative observation time. Children who received an ABO-incompatible transplant (n=364) were younger and a larger proportion had congenital heart disease and ventilator and mechanical circulatory support than the ABO-compatible recipients (n=1842). After matching, only differences in blood group (more O in ABO-incompatible and more AB in ABO-compatible groups) and use of polyclonal induction therapy with anti-thymocyte globulins persisted. The two matched groups had similar post-transplantation graft survival (p=0·74), freedom from coronary allograft vasculopathy (p=0·75), and malignancy (p=0·51). ABO-incompatible recipients showed longer freedom from rejection (p=0·0021) in the overall cohort, but not after matching (p=0·48). Severe infections (p=0·0007), bacterial infections (p=0·0005), and infections with polysaccharide encapsulated bacteria (p=0·0005) that share immunological properties with blood group antigens occurred less frequently after ABO-incompatible heart transplantation.
ABO-incompatible heart transplantation for children younger than 2 years is a clinically safe approach, with similar survival and incidences of rejection, coronary allograft vasculopathy, and malignancy to ABO-compatible recipients, despite higher-risk pre-transplant profiles. ABO-incompatible transplantation was associated with less bacterial infection, particularly encapsulated bacteria, suggesting that the acquired immunological changes accompanying ABO tolerance might benefit rather than jeopardise transplanted children.
Pediatric Heart Transplant Society.
ABO-incompatible heart transplant in pediatric population
2019, Cirugia Cardiovascular
El trasplante cardiaco ABO incompatible se inició en el año 2001 y desde entonces son varios los centros que han adoptado esta estrategia. Describimos los 2 primeros pacientes trasplantados en España con donante ABO incompatible, así como el protocolo utilizado.
El requisito fundamental para poder ser incluido en lista de trasplante cardiaco ABO incompatible establecido en nuestro centro, y de acuerdo con otros centros de más experiencia, es tener un título de isohemaglutininas menor o igual a 1:8. Son precisas determinaciones periódicas de isohemaglutininas y puede ser necesario realizar varias exanguinotransfusiones durante el trasplante. Tras el trasplante se mantendrá la siguiente política transfusional de por vida: hematíes del grupo receptor o grupo 0, plasma AB y plaquetas AB o lavadas.
Realizamos 2 trasplantes en nuestro centro con donante ABO incompatible. Ambos receptores presentaban un síndrome de cavidades izquierdas hipoplásicas tratados con procedimiento híbrido (stent en ductus y banding pulmonar). El primero evolucionó muy favorablemente, sin ninguna complicación durante su ingreso. El segundo presentó un rechazo cardiaco con compromiso hemodinámico que precisó asistencia en ECMO en el contexto de bajos niveles de tacrolimus y no relacionado con la incompatibilidad de grupo. Se realizaron 4 ciclos de plasmaféresis. La evolución posterior fue satisfactoria.
El trasplante ABO incompatible en pacientes con títulos de isohemaglutininas inferior o igual a 1:8 es una técnica segura que permite aumentar las probabilidades de trasplante, reduciendo su tiempo en lista de espera y, con ello, sus posibles complicaciones y mortalidad.
ABO-incompatible cardiac transplantation began in 2001 and since then there have been several centers that have adopted this strategy. We describe the first 2 patients transplanted in Spain with incompatible ABO donor as well as the protocol used.
The fundamental requirement to be included in the ABO-incompatible cardiac transplant list established in our center and according to other more experienced centers is to have an isohemagglutinin titre less than or equal to 1: 8. Periodic determinations of isohemagglutinins are required and it may be necessary to perform several exchange transfusions at the time of transplantation. After transplantation, the following transfusion policy will be maintained for life: red blood cells from the recipient group or group 0, plasma AB and platelets AB or washed.
We performed 2 transplants in our center with an incompatible ABO donor. Both recipients presented a hypoplastic left heart syndrome treated with a hybrid procedure (ductus stent and pulmonary banding). The first evolved very favorably without any complications during his admission. The second one presented a cardiac rejection with hemodynamic compromise that required ECMO assistance in the context of low levels of tacrolimus and not related to the group incompatibility. Four plasmapheresis cycles were performed. The subsequent evolution was satisfactory.
ABO-incompatible transplantation in patients with isohemagglutinin titrers less than or equal to 1:8 is a safe technique that increases the chances of transplantation, reducing their waiting list time and thus its possible complications and mortality.
C3d plasma levels and CD21 expressing B-cells in children after ABO-incompatible heart transplantation: Alterations associated with blood group tolerance
2014, Journal of Heart and Lung Transplantation
Most children transplanted with ABO-incompatible (ABOi) hearts develop selective tolerance to donor A/B antigens, whereas anti-A/B antibodies typically re-accumulate in adults after ABOi kidney transplantation. Deficiency of essential factors linking innate and adaptive immunity in early childhood may promote development of tolerance, specifically interactions between complement split product C3d and its ligand CD21 on B cells, considering their role in augmenting “T-independent” B-cell activation.
Blood and clinical data were analyzed from children after ABOi or ABO-compatible (ABOc) heart transplantation (HTx). Plasma C3d levels were quantified by enzyme-linked immunoassay. Peripheral blood mononuclear cells (PBMC) were phenotyped by flow cytometry; expression of B-cell co-receptor components CD21 and CD81 was quantified.
Fifty-five samples from pediatric HTx recipients (median age at transplant: 4.2 [range 0.03 to 20.4] months; age at sample collection: 14.6 [0.04 to 51.3] months; 53% ABOi) and 21 controls were studied. CD21-expressing B cells increased in trend with age (p = 0.079); longitudinal measures in individual patients showed a strong correlation with age. CD21 expression intensity in B-cells was not age-dependent. Plasma C3d levels did not correlate with age. Comparing ABOc vs ABOi HTx, CD21-expressing cell proportions were similar; however, serum C3d levels were significantly lower after ABOi HTx (p < 0.05).
In children, including HTx patients, CD21-expressing B-cells show a trend to increase with age, corresponding with improved responsiveness to polysaccharide antigens. This does not differ in patients with ABOi grafts developing tolerance to donor ABO antigens. C3d levels are not age-dependent, but reduced C3d levels after ABOi HTx suggest altered complement metabolism contributing to ABO tolerance.
Risk factors for mortality or delisting of patients from the pediatric heart transplant waiting list
2014, Journal of Thoracic and Cardiovascular Surgery
Current literature assessing factors associated with outcomes of patients waiting for pediatric heart transplants has focused on survival to transplant and mortality. Our aim was to determine risk factors associated with the outcomes of delisting, transplant, or death while waiting.
In this single-center, retrospective study of patients listed for heart transplants, competing risk analysis was used to model survival from listing to 4 competing outcomes (transplant, death, delisting for clinical deterioration, delisting for clinical improvement or surgical intervention).
There were 308 listing episodes in 280 patients. In competing risk analysis, 11% remained listed at 6 months (transplant 62%, dead 13%, delisted worse 6%, delisted improved 8%). Extracorporeal membrane oxygenation and ventricular assist devices were associated both with higher probability of transplant (hazard ratio [HR], 2.8; P < .001) and delisting for clinical deterioration (HR, 2.7; P = .06). Younger age at listing and complex congenital heart disease were shared risk factors for mortality (HR, 1.07; P = .05; HR, 2.9; P = .003) and delisting because of clinical deterioration (HR, 1.17; P = .01; HR, 2.8; P = .02). Younger age at listing and fetal listing were associated with delisting for clinical improvement or surgical intervention (HR, 1.13; P = .01; HR, 2.9; P = .02).
Overall survival to transplant depends on risk factors including age at listing, cardiac diagnosis, and mechanical circulatory support. Knowledge of risk factors for death and delisting for clinical deterioration or improvement can assist patient selection and timing of transplant listing.
Lung and heart allocation in the United States
2012, American Journal of Transplantation
Lung and heart allocation in the United States has evolved over the past 20–30 years to better serve transplant candidates and improve organ utilization. The current lung allocation policy, based on the Lung Allocation Score, attempts to take into account risk of death on the waiting list and chance of survival posttransplant. This policy is flexible and can be adjusted to improve the predictive ability of the score. Similarly, in response to the changing clinical phenotype of heart transplant candidates, heart allocation policies have evolved to a multitiered algorithm that attempts to prioritize organs to the most infirm, a designation that fluctuates with trends in therapy. The Organ Procurement and Transplantation Network and its committees have been responsive, as demonstrated by recent modifications to pediatric heart allocation and mechanical circulatory support policies and by ongoing efforts to ensure that heart allocation policies are equitable and current. Here we examine the development of US lung and heart allocation policy, evaluate the application of the current policy on clinical practice and explore future directions for lung and heart allocation.
Pushing the boundaries: The current status of ABO-incompatible cardiac transplantation
2012, Journal of Heart and Lung Transplantation
Citation Excerpt :
Data from the USA showed that there is a difference in listing times between children listed for ABOc and ABOi transplants. One study indicated that infants eligible for ABOi hearts have a median waiting time of 2 weeks less than those only listed for ABOc hearts.47 Another analysis showed a reduction in median waiting time (72 days for ABOc-listed patients compared with 54 days for ABOi-listed patients).49
Since the introduction of intentional ABO-incompatible (ABOi) cardiac transplantation in infants in the late 1990’s, the number of patients listed for and undergoing ABOi transplants has increased. This practice has been shown to lead to a reduction in waiting list mortality and increased utilisation of donor organs with equivalent outcomes to ABO-compatible transplants. Differences in the infant immune system provide a window of opportunity for ABOi transplantation. However it is increasingly clear that older patients and those with significant amounts of blood group antibody specific isohaemagglutinins may also benefit. Newer research is now focussing on longer term outcomes of ABOi transplants - in particular the development of graft accommodation or tolerance. This review assesses the current status of ABO-incompatible cardiac transplantation both in infants and in sensitized and older patients.

View all citing articles on Scopus

View full text

Featured articleEffect of ABO-Incompatible Listing on Infant Heart Transplant Waitlist Outcomes: Analysis of the United Network for Organ Sharing (UNOS) Database

Background

Methods

Results

Conclusions

Section snippets

Patient Population

Patient Demographics

Discussion

Disclosure Statement

Am J Translant

J Heart Lung Transplant

J Thorac Cardiovasc Surg

Am J Transplant

J Heart Lung Transplant

J Heart Lung Transplant

J Heart Lung Transplant

Featured article
Effect of ABO-Incompatible Listing on Infant Heart Transplant Waitlist Outcomes: Analysis of the United Network for Organ Sharing (UNOS) Database