Autoimmune cytopenias following alemtuzumab-induced renal transplant: clinical features and treatment outcomes

Abstract

The anti-CD52 monoclonal antibody, alemtuzumab, is used as induction therapy for renal transplantation. Its use has been associated with autoimmune manifestations, particularly autoimmune cytopenias (AICs). Here, we report a single-center, retrospective analysis of patients who developed AICs after an alemtuzumab-induced renal transplant. Over a period of 8 years, 40 renal transplant patients developed immune thrombocytopenia (ITP) (n=28), autoimmune hemolytic anemia (AIHA) (n=7) or Evans syndrome (ES) (n=5), with two peaks of incidence, at 18 and 36 months after alemtuzumab. Response and relapse rates to standard first-line ITP and AIHA therapy were comparable to primary forms, with two thirds requiring second-line agents. Most patients with ITP who failed to go into remission after steroids or IVIG received either rituximab or a thrombopoietin receptor agonist (TPO-RA). Compared to primary ITP, a higher response rate (91.6%) and median duration of response (56 months) were achieved with rituximab; and a higher proportion of patients were able to discontinue TPO-RAs and maintain remission (50%). Most patients experienced one or more adverse events, most commonly, infections (62.5%), cardiovascular diseases (27.5%) and deep vein thrombosis (25%).

In conclusion, AICs are a significant complication following alemtuzumab-induced renal transplantation, typically occurring within the 5-year period of immune reconstitution. Both rituximab and TPO-RAs show good efficacy, a few patients develop multi refractory disease, and the majority go into sustained remission off-treatment. Given that treatment is complicated by high rates of infections and thrombosis, supportive measures using antimicrobials as well as quick re-introduction of antiplatelet or anticoagulants in ITP and addition of anticoagulation in AIHA is recommended.