ABO-incompatible heart transplantation in early childhood: An international multicenter study of clinical experiences and limits

doi:10.1016/j.healun.2012.11.022

The Journal of Heart and Lung Transplantation

Volume 32, Issue 3, March 2013, Pages 285-292

https://doi.org/10.1016/j.healun.2012.11.022 Get rights and content

Background

Intentional blood group (BG)-incompatible (ABOi) heart transplantation in childhood is emerging in many centers. Safety limits remain undetermined. In this multicenter study we have compiled experience on clinical and immunologic boundaries.

Methods

Data from six centers in Europe and North America on ABOi transplantation were collected in a standardized survey.

Results

Fifty-eight ABOi transplants were performed in 57 patients. Median age at transplant was 6.8 months (0.03 to 90 months); post-transplant follow-up was 37.7 months (0.46 to 117 months), accumulating 188 patient-years. Forty-seven percent of the patients received pretransplant mechanical circulatory support. Donors were either blood group A (n = 25), B (n = 18) or AB (n = 15). The median peak antibody titer to the donor BG pretransplant was 1:8 (0 to 1:64) for anti-A and 1:4 (0 to 1:32) for anti-B. Titers against the donor BG were lower post- than pretransplant in B recipients (p = 0.02), whereas third-party antibodies in BG O recipients developed normally post-transplant. Induction immunosuppression included anti-thymocyte globulin (61%), basiliximab (32%) or none (7%). All patients received calcineurin inhibitors, including 62% with mycophenolate mofetil, 10% with azathioprine, 2% with everolimus and 24% with steroids. There were 4 episodes of cellular rejection (Grade≥2R) and 7 antibody-mediated rejections. Five patients underwent antibody removal post-transplant. One patient developed severe graft vasculopathy. Freedom from death or retransplantation was 100%/96%/69% at 1/5/10 years. No graft loss was attributed to BG antibodies.

Conclusions

Successful ABOi heart transplantation can be performed at an older age and with higher isohemagglutinin titers than initially assumed and using similar immunosuppressive regimens as for ABO-compatible transplants. Rejection and graft vasculopathy are rare. Persistently low titers of antibodies to the donor BG post-transplant suggest elements of tolerance and/or accommodation.

Section snippets

Methods

Approval from the human research ethics board of the University of Alberta, Edmonton, Canada, was obtained to perform an anonymized survey in children after ABOi heart transplantation. Confirmation or full ethics approval was obtained from the contributing centers. Data were collected in an anonymized questionnaire and included: patient demographics; donor–recipient BG; highest antibody titers to donor BG pre-, peri- and post-transplant; current and previously discontinued immunosuppressive

Results

Data were contributed on 58 transplants performed in 57 children between 2001 and 2010 from six centers in four countries and four donor organ allocation organizations: University of Alberta, Edmonton, Canada; Freeman Hospital, Newcastle upon Tyne and Great Ormond Street Hospital, London, UK; Ludwig Maximilians University Children’s Hospital, Munich, Germany; Children’s Memorial Hospital, Chicago, IL, USA; and Loma Linda University Children’s Hospital, Loma Linda, CA, USA.

Patient demographics

Discussion

The acceptance and implementation of a strategy of ABOi heart transplantation in early childhood still varies widely in different regions of the world. In this survey we have gathered together experiences from multiple centers in different countries to explore boundaries in the current clinical application for determining the extent to which ABOi transplantation appears safe in terms of age and immune maturity. Given the retrospective nature of this study, we have examined clinical information

Disclosure statement

The authors have no conflicts of interest to disclose.

References (28)

S.M. Pollock-BarZiv et al.
Competing outcomes after neonatal and infant wait-listing for heart transplantation
J Heart Lung Transplant
(2007)
M.D. Everitt et al.
Effect of ABO-incompatible listing on infant heart transplant waitlist outcomes: analysis of the United Network for Organ Sharing (UNOS) database
J Heart Lung Transplant
(2009)
S. Urschel et al.
Absence of donor-specific anti-HLA antibodies after ABO-incompatible heart transplantation in infancy: altered immunity or age?
Am J Transplant
(2010)
W.D. Park et al.
Accommodation in ABO-incompatible kidney allografts, a novel mechanism of self-protection against antibody-mediated injury
Am J Transplant
(2003)
A.I. Dipchand et al.
Equivalent outcomes for pediatric heart transplantation recipients: ABO-blood group incompatible versus ABO-compatible
Am J Transplant
(2010)
S.L. Roche et al.
Multicenter experience of ABO-incompatible pediatric cardiac transplantation
Am J Transplant
(2008)
R. Kirk et al.
The registry of the International Society for Heart and Lung Transplantation: thirteenth official pediatric heart transplantation report—2010
J Heart Lung Transplant
(2010)
J.B. Sorensen et al.
Transplantation of ABO group A2 kidneys from living donors into group O and B recipients
Am J Transplant
(2001)
J. Conway et al.
Development of donor-specific isohemagglutinins following pediatric ABO-incompatible heart transplantation
Am J Transplant
(2012)
M.J. O'Connor et al.
Ventricular assist device-associated anti-human leukocyte antigen antibody sensitization in pediatric patients bridged to heart transplantation
J Heart Lung Transplant
(2010)

L.J. West et al.

ABO-incompatible heart transplantation in infants

N Engl J Med

(2001)

L.J. West

B-cell tolerance following ABO-incompatible infant heart transplantation

Transplantation

(2006)

C.S. Almond et al.

Impact of ABO-incompatible listing on wait-list outcomes among infants listed for heart transplantation in the United States: a propensity analysis

Circulation

(2010)

X.H. Fan et al.

Donor-specific B-cell tolerance after ABO-incompatible infant heart transplantation

Nature Med

(2004)

Cited by (69)

ABO-Incompatible Heart Transplantation: Where Science, Society, and Policy Collide
2024, Journal of Cardiac Failure
Consensus statement on heart xenotransplantation in children: Toward clinical translation
2023, Journal of Thoracic and Cardiovascular Surgery
The International Society for Heart and Lung Transplantation (ISHLT) guidelines for the care of heart transplant recipients
2023, Journal of Heart and Lung Transplantation
ABO blood group antigens and differential glycan expression: Perspective on the evolution of common human enzyme deficiencies
2023, iScience
Enzymes catalyze biochemical reactions and play critical roles in human health and disease. Enzyme variants and deficiencies can lead to variable expression of glycans, which can affect physiology, influence predilection for disease, and/or directly contribute to disease pathogenesis. Although certain well-characterized enzyme deficiencies result in overt disease, some of the most common enzyme deficiencies in humans form the basis of blood groups. These carbohydrate blood groups impact fundamental areas of clinical medicine, including the risk of infection and severity of infectious disease, bleeding risk, transfusion medicine, and tissue/organ transplantation. In this review, we examine the enzymes responsible for carbohydrate-based blood group antigen biosynthesis and their expression within the human population. We also consider the evolutionary selective pressures, e.g. malaria, that may account for the variation in carbohydrate structures and the implications of this biology for human disease.
Congenital Heart Disease
2023, Avery's Diseases of the Newborn
Congenital heart disease (CHD) is the most common birth defect encountered in the clinical setting. The prevalence of all forms of congenital heart lesions is approximately 1% of live births, although estimates in the newborn are likely compromised by underdiagnosis of some lesions such as bicuspid aortic valve and overdiagnosis of normal structures that are in transition, including the foramen ovale and ductus arteriosus. The presentation of the newborn with CHD can range from being asymptomatic to complete cardiovascular collapse. The presentation of neonates with CHD is vast and can range from murmurs to cyanosis, and/or congestive heart failure (CHF). Lesions that result in each of these clinical findings will be considered separately although considerable overlap exists among the three groups.
Neonatal heart transplant outcomes: A single institutional experience
2021, Journal of Thoracic and Cardiovascular Surgery
Neonatal orthotopic heart transplantation was introduced in the 1980s as a treatment for complex congenital heart disease. Progress in single-ventricle palliation and biventricular correction has resulted in a decline in neonatal heart transplant volume. However, limited reports on neonatal heart transplants have demonstrated favorable outcomes. We report the long-term outcomes of patients with neonatal heart transplants at our institution spanning nearly 30 years.
A retrospective analysis of neonatal heart transplants and neonates listed for transplant was performed at Children's Hospital Colorado. Primary outcomes were early and late survival. Secondary outcomes were rejection episodes, retransplantation, and development of cardiac allograft vasculopathy or post-transplant lymphoproliferative disease.
A total of 21 neonates underwent orthotopic heart transplantation at our institution. Among these, 10 neonates were transplanted from 1991 to 2000, 8 neonates were transplanted from 2001 to 2010, and 3 neonates were transplanted from 2011 to 2020. The average age of these patients was 17 days, and the average weight was 3.43 kg. Early survival was 95.2%. Survival at 1 and 5 years was 85.7% (confidence interval [CI], 61.9%-95.2%) and 75% (CI, 45.6%-85.5%), respectively. Of eligible patients, the 10-year and 20-year survival was 72.2% (CI, 45.1%-85.3%) and 50% (CI, 25.9%-70.1%), respectively.
Our institution reports favorable outcomes of neonatal heart transplantation. These results should be considered within the context of outcomes for patients awaiting transplant and the limited donor availability. However, the successful nature of these procedures suggest it may be necessary to reevaluate the indications for neonatal heart transplantation, particularly where risk of mortality and morbidity with palliative or corrective surgery is high.

View all citing articles on Scopus

View full text

ABO-incompatible heart transplantation in early childhood: An international multicenter study of clinical experiences and limits

Background

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Disclosure statement

J Heart Lung Transplant

J Heart Lung Transplant

Am J Transplant

Am J Transplant

Am J Transplant

Am J Transplant

J Heart Lung Transplant

Am J Transplant

Am J Transplant

J Heart Lung Transplant

ABO-incompatible heart transplantation in infants

N Engl J Med

B-cell tolerance following ABO-incompatible infant heart transplantation

Transplantation

Impact of ABO-incompatible listing on wait-list outcomes among infants listed for heart transplantation in the United States: a propensity analysis

Circulation

Donor-specific B-cell tolerance after ABO-incompatible infant heart transplantation

Nature Med