Rituximab-based Induction in Vascularized Composite Allotransplantation: Prolonged Rejection-free Survival and the Role of Donor-specific Antibodies

Background: Vascularized composite allotransplantation (VCA) restores form and function in patients with severe disfigurement, yet acute rejection remains common within the first year. In solid organ transplantation, rituximab, a B cell-depleting agent, has been shown to reduce rejection in highly sensitized recipients, and donor-specific antibodies (DSAs) are established biomarkers of rejection. The impact of rituximab and DSAs in VCA remains unclear. This study examined rejection-free survival following rituximab induction and the relationship between positive DSA levels and rejection in VCA recipients. Methods: This retrospective review analyzed 4 patients who underwent facial transplantation between 2015 and 2023 at our institution. All patients received rituximab and antithymocyte globulin as part of their induction immunosuppression. Rejection-free survival was the primary outcome, with DSA levels assessed at baseline and throughout follow-up. A generalized linear mixed-effects model was used to evaluate the relationship between DSA positivity and rejection. Results: = 0.693). Some patients were DSA-negative during clinical rejection, and some were DSA-positive without signs of rejection. Conclusions: This is the first study to evaluate rituximab-based induction in a cohort of VCA recipients, demonstrating median rejection-free survival exceeding one and a half years. Although some patients were DSA-positive during rejection episodes, no significant correlation was observed, challenging the predictive value of DSAs as seen in solid organ transplantation and highlighting the need to explore alternative biomarkers for rejection in VCA.