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

Simon Urschel, Ingrid M. Larsen, Richard Kirk, Julie Flett, Michael Burch, Nadine Shaw, Julia Birnbaum, Heinrich Netz, Elfriede Pahl, Kathleen L. Matthews, Richard Chinnock, Joyce K. Johnston, Kim Derkatz, Lori J. West

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)285-292
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume32
Issue number3
DOIs
StatePublished - Mar 1 2013

Fingerprint

Heart Transplantation
Multicenter Studies
Blood Group Antigens
Transplants
Antibodies
Mycophenolic Acid
Antilymphocyte Serum
Azathioprine
Graft Rejection
Hemagglutinins
Immunosuppressive Agents
North America
Immunosuppression
Transplantation
Steroids
Tissue Donors
Safety

Keywords

  • ABO incompatible
  • antibodies
  • blood groups
  • children
  • heart transplantation
  • immature immune system
  • mechanical circulatory support
  • tolerance

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

Cite this

ABO-incompatible heart transplantation in early childhood : An international multicenter study of clinical experiences and limits. / Urschel, Simon; Larsen, Ingrid M.; Kirk, Richard; Flett, Julie; Burch, Michael; Shaw, Nadine; Birnbaum, Julia; Netz, Heinrich; Pahl, Elfriede; Matthews, Kathleen L.; Chinnock, Richard; Johnston, Joyce K.; Derkatz, Kim; West, Lori J.

In: Journal of Heart and Lung Transplantation, Vol. 32, No. 3, 01.03.2013, p. 285-292.

Research output: Contribution to journalArticle

Urschel, S, Larsen, IM, Kirk, R, Flett, J, Burch, M, Shaw, N, Birnbaum, J, Netz, H, Pahl, E, Matthews, KL, Chinnock, R, Johnston, JK, Derkatz, K & West, LJ 2013, 'ABO-incompatible heart transplantation in early childhood: An international multicenter study of clinical experiences and limits', Journal of Heart and Lung Transplantation, vol. 32, no. 3, pp. 285-292. https://doi.org/10.1016/j.healun.2012.11.022
Urschel, Simon ; Larsen, Ingrid M. ; Kirk, Richard ; Flett, Julie ; Burch, Michael ; Shaw, Nadine ; Birnbaum, Julia ; Netz, Heinrich ; Pahl, Elfriede ; Matthews, Kathleen L. ; Chinnock, Richard ; Johnston, Joyce K. ; Derkatz, Kim ; West, Lori J. / ABO-incompatible heart transplantation in early childhood : An international multicenter study of clinical experiences and limits. In: Journal of Heart and Lung Transplantation. 2013 ; Vol. 32, No. 3. pp. 285-292.
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AU - Flett, Julie

AU - Burch, Michael

AU - Shaw, Nadine

AU - Birnbaum, Julia

AU - Netz, Heinrich

AU - Pahl, Elfriede

AU - Matthews, Kathleen L.

AU - Chinnock, Richard

AU - Johnston, Joyce K.

AU - Derkatz, Kim

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N2 - 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.

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