Introduction: ABO-incompatible liver transplantation (ABOi LT) is a critical alternative in pediatric liver transplantation due to organ scarcity. However, ABOi LT remains prone to antibody-mediated rejection (ABMR), which can lead to graft loss despite standard treatments. Daratumumab, an anti-CD38 monoclonal antibody, has shown promise in managing ABMR in other organ transplants, but its role in ABOi LT remains unexplored.
Methods: We report the case of two pediatric patients with acute liver failure that received an ABO-incompatible liver graft.
In both cases the indication for a super-urgent LT was acute liver failure. The first case was a 13-years-old boy for which the cause of liver failure kept unknown. Given his critical condition and lack of compatible donors worsen by SARS-CoV-2 pandemic, he received an ABOi whole liver graft from a deceased donor (blood group A2, recipient blood group O). The second case was a 14-years old girl that underwent paracetamol overdose that also received a liver graft from a deceased donor (blood group A, recipient blood group O).   
In both cases, patients underwent pre-transplant rituximab administration and plasma-exchange to reduce anti-A isoagglutinin titers below 1/16. Post-transplant immunosuppression was managed with basiliximab, high-dose steroids, tacrolimus, mycophenolate mofetil, multiple plasma-exchange and IVIG infusions. Despite these therapies, ABMR was diagnosed based on rising anti-A titers (1/32 for the boy, 1/128 for the girl, goal 1/16), abnormal liver tests, intra-hepatic biliary dilatation and liver biopsy. After multidisciplinary discussion, daratumumab was introduced. Four weekly infusions resulted in significant improvement in liver function and anti-A titers (1/4 for the boy, 1/8 for the girl).
For the first case, follow-up biopsies at 2 years showed no signs of rejection, and mild T-cell mediated rejection (TCMR) at 1 year was treated successfully with corticosteroids. Over 4 years, liver function remained normal, and no biliary dilatation or side effects were observed. For the second case we have a shorter follow-up. Anyways, biopsy at 20 post-operative days showed the absence of both cellular and antibody-mediated rejection and the patient was discharged with a normal liver function.
Conclusion: Daratumumab was effective in managing refractory ABMR, likely by reducing both blood-type antibodies and donor-specific anti-HLA antibodies. These cases highlight daratumumab’s potential in ABOi LT, especially in overcoming ABMR when standard therapies fail. Further research is needed to confirm its efficacy across blood groups and optimize management strategies for ABMR.