ABO-Incompatible Heart Transplantation in Older Children Using Immune Modulation

Abstract

Purpose ABO-incompatible (ABOi) heart transplantation (HTx) has become a standard approach for infants with low isohemagglutinin titers (ISO). ABOi HTx may also be safe for older pediatric patients with altered immune response, however, thresholds are yet to be defined. Methods Data on management, clinical course and ISO were analyzed from two patients undergoing ABOi HTx beyond infancy. Results A 4-yr old ABO-O girl with hypoplastic left heart syndrome developed refractive protein-losing enteropathy, effusions and edema shortly after Fontan palliation, in the context of AV valve regurgitation and ventricular dysfunction. She was listed for HTx and deemed high-risk due to elevated pulmonary vascular resistance, HLA sensitization (cPRA 81 %), and need for ventilatory support. Despite her age, ISO titers were only moderately high (anti-A 1:32; anti-B 1:16); she underwent ABOi HTx (donor ABO-B) with plasmapheresis, ATG and methylprednisolone induction which was expanded for rituximab and IVIG. She required temporary right ventricular support and dialysis after HTx. Immunosuppression was maintained with tacrolimus and mycophenolate mofetil (MMF), modified during the clinical course to now receiving sirolimus / MMF for the past 6 years. Her B-ISO titres never exceeded 1:2 post-transplant. She remains free of rejection and graft vasculopathy now 9.5 years post-HTx. Another 4-yr old ABO-O girl with microdeletion 22q11 syndrome, pulmonary atresia, ventricular septal defect and MAPCAs sustained coronary artery injury resulting in ventricular dysfunction, requiring ECMO followed by milrinone dependency. She was listed for HTx and was highly HLA sensitized (cPRA 92%). Desensitisation was initiated with rituximab and IVIG; her A-ISO (peak anti-A 1:128) dropped to 1:16 at which point her listing was opened to ABOi. She received an ABOi HTx (donor ABO-A) at age 5 11/12 years, not crossing donor-specific HLA antibodies, receiving plasma exchange, ATG induction and methylprednisolone. Maintenance therapy included tacrolimus and MMF. She remains free of rejection now 1.5 years post-HTx with anti-A titre never exceeding 1:4. Conclusion ABOi HTx can be performed safely in selected older pediatric patients if ISO are low even secondary to immune manipulation. This approach may offer a long-term HTx option for older children who are highly sensitized or in urgent need of transplantation.