ABO-Incompatible Lung Transplantation in an Infant

Waitlist mortality continues to be a limiting factor for all solid-organ transplant programs. Strategies that could improve this situation should be considered. We report the first ABO-incompatible lung transplantation in an infant. The recipient infant was ABO blood group A1 and the donor group B. The recipient was diagnosed with surfactant protein B deficiency, which is a fatal condition and lung transplantation is the only definitive therapy. At 32 days of age, a bilateral lung transplantation from a donation after cardiac death (DCD) donor was performed. Intraoperative plasma exchange was the only preparatory procedure performed. No further interventions were required as the recipient isohemagglutinins were negative before transplant and have remained negative to date. At 6 months posttransplant, the recipient is at home, thriving, with normal development. This outcome suggests that ABO-incompatible lung transplantation is feasible in infants, providing another option to offer life-saving lung transplantation in this age range. Waitlist mortality continues to be a limiting factor for all solid-organ transplant programs. Strategies that could improve this situation should be considered. We report the first ABO-incompatible lung transplantation in an infant. The recipient infant was ABO blood group A1 and the donor group B. The recipient was diagnosed with surfactant protein B deficiency, which is a fatal condition and lung transplantation is the only definitive therapy. At 32 days of age, a bilateral lung transplantation from a donation after cardiac death (DCD) donor was performed. Intraoperative plasma exchange was the only preparatory procedure performed. No further interventions were required as the recipient isohemagglutinins were negative before transplant and have remained negative to date. At 6 months posttransplant, the recipient is at home, thriving, with normal development. This outcome suggests that ABO-incompatible lung transplantation is feasible in infants, providing another option to offer life-saving lung transplantation in this age range. Lung transplantation is effective life-saving treatment for selected children (1Solomon M Grasemann H Keshavjee S Pediatric Lung Transplantation.Pediatric Clin North Am. 2010; 57: 375-391Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar) and adults with end-stage lung diseases, but the number of patients waiting for a lung transplant greatly exceeds the number of available donor organs. The current donor shortage encourages us to pursue approaches that increase the availability of donor organs. Current strategies include donation after cardiac death (DCD), utilization of ex vivo evaluation and treatment of extended donor organs (2Cypel M Yeung JC Liu M et al.Normothermic ex vivo lung perfusion in clinical lung transplantation.N Engl J Med. 2011; 364: 1431-1440Crossref PubMed Scopus (771) Google Scholar) and living related lung donors. Size mismatch is a problem for small patients in need of lung transplantation, including infants and when an organ of small size becomes available, often these organs cannot be utilized because of blood group incompatibility. The waitlist mortality for infants has to date been discouragingly high. As previously described from our center (3West LJ Pollock-Barziv SM Dipchand AI et al.ABO-incompatible heart transplantation in infants.N Engl J Med. 2001; 344: 793-800Crossref PubMed Scopus (359) Google Scholar), with appropriate immunological preparation and management, ABO-incompatible heart transplantation is clinically achievable in infants with long-term success. Here, we report the first ABO-incompatible lung transplantation in an infant. This case report illustrates a potential means of increasing the donor pool for infant lung transplant candidates. The lung transplant recipient was born at 38 weeks gestational age with a birth weight of 3720 g. He developed cyanosis and respiratory distress by 1 h of age, necessitating intubation and mechanical ventilation. Deterioration in respiratory status required high frequency oscillation and high oxygen supplementation. Genetic testing confirmed a diagnosis of surfactant protein B deficiency, which is fatal without lung transplantation. At the age of 4 weeks, he was referred to our center for lung transplantation. Within 5 days of listing, a size-matched DCD donor became available. However, the donor was ABO-incompatible. The recipient infant was ABO blood group A1+ and the donor B–. With parental consent, an ABO-incompatible bilateral lung transplant was performed through a clamshell incision at 32 days of age. Recipient isohemagglutinins and HLA antibodies were negative at the time of transplantation. Plasma exchange of 1.5×, the recipient blood volume was performed intraoperatively as per the infant ABO-incompatible heart transplant protocol at our center. No other preparatory procedures were performed. Postoperative immunosuppression included basiliximab (induction), tacrolimus, mycophenolate mofetil and methylprednisolone. The immunosuppression regimen was based on our infant lung transplant protocol, as opposed to the infant heart transplant protocol which utilizes thymoglobulin. No graft dysfunction occurred and the infant was extubated on the fifth postoperative day. Supraventricular tachycardia requiring adenosine occurred on postoperative day 8, followed by episodes of atrial ectopic tachycardia that resolved on propranolol. Isohemagglutinins were assessed according to our center’s ABO-incompatible heart transplant protocol (daily for 7 days, weekly for 3 weeks, biweekly for 2 months, monthly for 4 months and every 3–6 months thereafter). At 6 months posttransplant, the recipient’s anti-B isohemagglutinins remain negative. He has not had any episodes of graft rejection, based on transbronchial lung biopsies taken at 7 weeks, 3 months, 6 months posttransplant. He is thriving (height: 25–50th percentile, weight: 25th percentile), is developmentally appropriate and has normal expiratory flows on infant pulmonary function testing at 4 months and 6 months posttransplant. Transplantation of the lungs from ABO-incompatible donors is not intentionally performed as standard clinical practice because of the risk of hyperacute and acute antibody mediated rejection. The few available reports on ABO-incompatible lung transplantation generally discuss cases that have occurred in adults because of clerical errors (4Pierson 3rd, RN Loyd JE Goodwin A et al.Successful management of an ABO-mismatched lung allograft using antigen-specific immunoadsorption, complement inhibition, and immunomodulatory therapy.Transplantation. 2002; 74: 79-84Crossref PubMed Scopus (55) Google Scholar, 5Banner NR Rose ML Cummins D et al.Management of an ABO-incompatible lung transplant.Am J Transplant. 2004; 4: 1192-1196Crossref PubMed Scopus (32) Google Scholar, 6Patel M Carby M Rice A Cummins D Banner NR Medium-term outcome of an ABO incompatible lung transplant.Am J Transplant. 2010; 10: 702-703Crossref PubMed Scopus (6) Google Scholar, 7Campion EW The Death at Duke.N Engl J Med. 2003; 348: 1083-1084Crossref PubMed Scopus (34) Google Scholar). Only one intentional ABO-incompatible lung transplantation has been reported. It was performed in a 21-year-old cystic fibrosis patient who was mechanically ventilated and on arterio–venous interventional lung assist (Novalung; Novalung GmbH, Heilbronn, Germany). The recipient was blood group O and because timely allocation was believed to be impossible, a donor with blood group AB was accepted (8Strüber M Warnecke G Hafer C et al.Intentional ABO-incompatible lung transplantation.Am J Transplant. 2008; 8: 2476-2478Crossref PubMed Scopus (25) Google Scholar). An intense antibody depletion protocol, based on algorithms from ABO-incompatible kidney transplantation, using plasmapheresis, IVIG, rituximab and immunoadsorption, was required. She was reported to be well at 9 months posttransplant. To our knowledge, this is the first ABO-incompatible lung transplant performed in an infant. This option was considered in our patient because infant ABO-incompatible heart transplantation is now considered routine in some centers, including ours, with excellent early and long-term results. Since 1996, infants referred for cardiac transplant at the Hospital for Sick Children in Toronto have been offered the heart from the first available donor of compatible size, regardless of blood type (3West LJ Pollock-Barziv SM Dipchand AI et al.ABO-incompatible heart transplantation in infants.N Engl J Med. 2001; 344: 793-800Crossref PubMed Scopus (359) Google Scholar). In this experience, in the absence of preformed antibodies against blood group antigens, hyperacute and acute antibody mediated rejection did not occur. Besides intraoperative plasma exchange during cardiopulmonary bypass, no additional treatment or procedure is required as long as the isohemaggutinin levels remain negative. Within 5 years of the adoption of a strategy to accept ABO-incompatible donor hearts for infants at the Hospital for Sick Children, the waitlist mortality rate in infants aged younger than 6 months waiting for heart transplantation decreased from 58% to 7% (3West LJ Pollock-Barziv SM Dipchand AI et al.ABO-incompatible heart transplantation in infants.N Engl J Med. 2001; 344: 793-800Crossref PubMed Scopus (359) Google Scholar). This impressive drop was not seen in the review of United Network for Organ Sharing (UNOS) data, most likely because of the difference in allocation algorithms in each country (9Everitt MD Donaldson AE Casper TC 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; 28: 1254-1260Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar). More recently, our center reported that over a 10-year period, 43% of their infant heart transplants are ABO-incompatible and have outcomes that are indistinguishable from those of the ABO-compatible recipients (10Dipchand AI Pollock BarZiv SM Manlhiot C West LJ VanderVliet M McCrindle BW Equivalent outcomes for pediatric heart transplantation recipients: ABO-blood group incompatible versus ABO-compatible.Am J Transplant. 2010; 10: 389-397Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar). The long-term success of ABO-incompatible infant heart transplantation is likely because of several reasons. Some infants do not develop antigraft antibodies, likely because of acquired donor-specific B-cell tolerance. This is thought to be achieved by elimination of donor-specific B lymphocytes through persistent exposure to donor antigens during an immunologically susceptible window (11Fan X Ang A Pollock-Barziv SM et al.Donor-specific B-cell tolerance after ABO-incompatible infant heart transplantation.Nat Med. 2004; 10: 1227-1233Crossref PubMed Scopus (177) Google Scholar). Other infants show low-levels of antigraft antibodies, but no evidence of graft dysfunction. This may be related to the development of graft cell resistance to humoral injury (12Takahashi K Accomodation in ABO-incompatible kidney transplantation: Why do kidney grafts survive?.Transplant Proc. 2004; 36: 193S-196SCrossref PubMed Scopus (50) Google Scholar) or to a reduction in the binding effectiveness of the antibodies to donor cells to allow accommodation of the transplant (13Ishida H Tanabe K Ishizuka T et al.The mechanism responsible for accomodation after living-related kidney transplantations across the blood barrier.Transpl Int. 2005; 18: 716-720Crossref PubMed Scopus (15) Google Scholar). The current shortage of infant donor lungs encourages us to look at all potential options to increase the donor pool. Here, we report on an infant with an ABO-incompatible lung transplantation using a DCD donor. The use of DCD donors is routine in some centers, but is infrequently utilized in pediatric patients (14Yoo PS Olthoff KM Abt PL Donation after cardiac death in pediatric organ transplantation.Curr Opin Organ Transpl. 2011; 16: 483-488Crossref PubMed Scopus (26) Google Scholar); and to our knowledge, there is no reported case of a DCD lung transplantation in an infant. In addition, our case illustrates that ABO-incompatible lung transplantation can be safely performed in young infants. Both DCD and ABO-incompatible transplantation can be used to increase the donor organ pool to offer life-saving lung transplantation in this age group. The authors gratefully acknowledge Dr. Lori West for her innovation and development of ABO-incompatible heart transplant protocols, Dr. Anne Dipchand and the perfusionists from the Sickkids heart transplant program, for their advice and help at the time of the transplant. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

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