PURPOSE:Antibodies directed against donor human leukocyte antigens (HLA) are believed to contribute to the development of acute and chronic allograft rejection after lung transplantation. Despite increasing recognition of the importance of humoral sensitization in allograft rejection, its treatment remains controversial. Rituximab (RIT), a humanized monoclonal antibody directed to the antigen CD20, has been used successfully in the management of humoral rejection in other solid organ transplant recipients; however, no studies have defined its role in lung transplantation. The purpose of this study is to evaluate the efficacy of RIT therapy upon anti-HLA antibodies, including donor specific antibody (DSA), in a cohort of consecutively treated lung transplant recipients.
METHODS:Thirty lung transplant recipients with de novo anti-HLA antibodies detected by flow cytometry were treated with a single 375mg/m2 rituximab dose. The pre- and post-RIT panel of reactive antibody (PRA) values were compared using the paired Wilcoxon signed-rank test, and percentage with pre- and post-DSA using McNemar’s test for paired binary samples.
RESULTS:Patients received RIT after development of de novo anti-HLA antibodies at a mean 560 days after transplant. A significant decrease in the percentage of class I PRA reactivity was observed following treatment (median pretreatment 16% vs. posttreatment 0%, p=0.0001). Class II PRA reactivity was also significantly decreased following RIT (median pretreatment 14.5% vs. posttreatment 2%, p=0.005). Additionally, the number of patients with DSA was significantly decreased after RIT. Seventy percent (21/30) exhibited DSA prior to treatment compared to 20% (6/30) after rituximab (p=0.0001).
CONCLUSION:RIT therapy significantly reduces both Class I and Class II PRA in lung transplant recipients as well as DSAs. Additional studies are needed to determine the long-term safety of RIT in this population and determine if the reduction in PRA reactivity and DSA leads to improved long-term allograft outcomes and patient survival.
CLINICAL IMPLICATIONS:RIT appears to be a useful therapy in lung transplant recipients with donor specific antibodies.
DISCLOSURE:Travis Dick, No Financial Disclosure Information; No Product/Research Disclosure Information