Safety of Cumulative Dose Anti-Thymocyte Globulin in Lung Transplant

Abstract

<h3>Purpose</h3> The optimal dose of anti-thymocyte globulin (ATG) in kidney transplant is well established, however, dosing of ATG in lung transplant (LTx) is not well defined. LTx patients have a more delicate balance between infection and rejection given higher immunosuppression goals and constant exposure of the graft to the external environment. We sought to evaluate the optimal dose (mg/kg) of ATG in LTx patients. <h3>Methods</h3> LTx patients who received ≥1 dose of ATG between 6/2016 and 9/2019 were categorized based on indication (induction, treatment of rejection, or treatment of chronic allograft dysfunction (CLAD)). Cumulative dose (mg/kg) was calculated using actual weight at time of ATG. Safety endpoints following the last ATG dose included infection ≤1 year and malignancy until last follow-up. <h3>Results</h3> ATG indications were induction (n=11, 24%), rejection (n=21, 47%), and CLAD (n=13, 29%). Median doses (mg/kg) were: 3.2 for induction, 4.9 for rejection, and 4.2 for CLAD. Bacterial infections occurred in 23 patients (51%) (1 clinically significant urinary tract infection requiring intravenous antibiotics, 12 blood stream, and 19 respiratory) at a median of 38 days (d) after last ATG dose; viral infections occurred in 11 patients (24%) with cytomegalovirus viremia being the most common; fungal infections occurred in 27 patients (60%). The most common organisms identified were Pseudomonas and Aspergillus species. Four patients (9%) developed malignancy at a median of 339d, including 3 cases of cutaneous malignancy and 1 case of small cell lung cancer. <h3>Conclusion</h3> Safety concerns with ATG in LTx include infection and malignancy with a possible dose-correlated risk. We found a >50% incidence of both bacterial and fungal infections following ATG; those who received ATG for induction experienced the highest rates (64% bacterial, 73% fungal). The high incidence of infections supports using lower cumulative doses, however, further evaluation into the ideal dosing threshold to balance safety and efficacy within each ATG indication is warranted.