317.1: Personalized Approach to Risk-Stratified Desensitization in Modified Multivisceral Transplantation

Introduction: Human leukocyte antigen (HLA) allosensitization prolongs waitlist times and can increase the risk of rejection and both graft and patient loss for intestinal transplant candidates. Desensitization offers a potential therapeutic option to facilitate transplantation with a more compatible donor however there is paucity of evidence on the field. We aim to describe a case of personalized approach to risk-stratified desensitization in a modified non-liver multivisceral transplant (MVT) candidate with cPRA of 100%. Method: A 45 y.o female with history of multiple severe gastroparesis and pseudoobstruction on chronic parenteral nutrition, sensitized via multiple blood transfusions and pregnancy x 2 actively listed for modified MVT was prospectively follow up to determined risk stratification desensitization based on HLA and C1q antibodies (Ab) tests. She underwent desensitization with Rituximab 375 mg/m2 x 1, therapeutic plasma exchange (TPE) x 5 sessions in March 2021 followed by 2 g/k monthly IVIG x 6. We report her follow up at 12 months since the therapy. Results: Before starting desensitization strategies, she tested positive for T and B cell virtual cross match (VCM) with all her donor offers. Her cPRA was 100 % with 54% for Class I (dominant HLA Ab: B7: 22775 MFI) and 63 % of class II (dominant HLA Ab: DR17: 21021 MFI). Following desensitization strategy, we identify using C1q test her dominants HLA Ab as B7, B81 and DR4 with 17321, 8619 and 3133 MFIs respectively; therefore, they were classified as unacceptable antigens. A donor’s offer was accepted when her HLA ab were deemed appropriate in the context of T cell VXM negative and the expected B cell VXM positive (6. 48 ratio) by flow cytometry. She underwent modified MVT in August 2021. The patient received induction immunosuppression with Methylprednisolone taper, Rituximab 150 mg/m2, anti-thymoglobulin 2 mg/kg x 5 doses, TPE x 5 sessions, Vedolizumab 300 mg IV 10, 30 and 60 days posttransplant. Her current maintenance immunosuppression is with tacrolimus (target trough level: 8-10 ng/ml now 7 months post transplant), mophetil mycophenolate 500 mg twice daily and prednisone taper to 5 mg daily. Her dominant donor specific antibody (DSA) was DR 7, which decreased on pre-transplant sample from 13982 to 3053 MFI post induction treatment a week after finishing TPE. The patient’s protocol biopsies showed no evidence of rejection. At 7 months post -transplant her DR7 DSA remains low at 1576 MFI and there is no evidence of de novo DSA. Conclusion: We described the use of personalized approach to risk-stratified desensitization that lead to accept an organ offer based on HLA and C1q antibodies test follow by tailored immunosuppression strategies with early successful results. Further studies are needed to reproduce our outcomes.