Retrospective Review of Use of Individualized Dosing of Rabbit Anti-Thymocyte Globulin on Outcomes in Pediatric Post Allogeneic Stem Cell Transplant Patients: A Single Center Experience

Abstract

Background Allogeneic hematopoietic stem cell transplantation (aHSCT) is a curative treatment for numerous benign and malignant hematologic and immunological processes. Rabbit anti-thymocyte globulin (rATG) was introduced into conditioning regimens to reduce the risk of GVHD and graft failure. High exposure (AUC) of rATG before stem cell infusion leads to reduced graft failure and GVHD while low post-transplant exposure (AUC) is associated with improved T-cell reconstitution. Initial lymphocyte counts also affect the exposure to rATG. Hence the dosing and timing of rATG is crucial to balance the risks and benefits of rATG. At our center in the United States, we implemented individualized dosing and timing of rATG like that previously reported by authors in the Netherlands. ATG dosing is based on body weight, stem cell source, and absolute lymphocyte. Objectives To study rates of overall survival (OS), graft failure and acute and chronic GvHD in patients who received individualized dosing of rATG Methods We performed a retrospective chart review of consecutive pediatric patients who underwent aHSCT between January 2015 and June 2018 and received rATG (Thymoglobulin). All patients received individualized ATG dosing. Results A total of 18 patients were included (median age-9 years, range 15 months to 21 years; 14 malignant, 4 non-malignant); matched sibling (n=1), unrelated (n= 10 complete match, n=5 mismatched 9/10, n=1 mismatched 7/8) and haplo-identical transplant (n=1). Graft source included bone marrow (n=15), peripheral blood stem cells (n=2) and cord blood (n=1). Conditioning regimens were variable depending on donor source and indication for transplant, with fludarabine, busulfan and rATG being the most commonly utilized regimen (50%). GVHD prophylaxis for most patients was tacrolimus with mini-methotrexate. Seventeen of the 18 transplants resulted in neutrophil engraftment at a median of 17 days (1 graft failure: 6%; who died in neutropenia of fungal infection). One patient relapsed after +100d. Severe acute GVHD (≥ grade III) occurred in 1/18 patients (6%) while grade II-IV acute GVHD was noted in 4 patients (23%). Five patients developed chronic GVHD, but only two developed extensive cGVHD (12%), one of which was known to be due to non-compliance of medications. Overall survival for our cohort is 88%, with a median follow up of 1.3 years. Conclusion Use of an individualized dosing of rATG is feasible in a pediatric aHSCT patient population and resulted in minimal acute and chronic graft versus host disease with very little graft failure in patients undergoing aHSCT for a wide variety of indications. Our results compare favorably with those of authors first reporting this approach to rATG dosing.