Determining the best premedication regimen to prevent rabbit anti-human thymocyte globulin infusion-associated reactions: A retrospective study comparing two hematopoietic stem cell transplant centers

Abstract

Background

Thymoglobulin® (ATG), a rabbit anti-human thymocyte globulin, is used in allogeneic hematopoietic stem cell transplantation (HSCT) mainly to prevent the development of graft-versus-host disease (GVHD). Three doses (ATG1, ATG2, and ATG3) are administered on separate days, apart from the graft day. Since infusion-associated reactions (IAR) are frequent, patients were treated with acetaminophen, antihistamine, and corticosteroids (CS) as premedication (PR); however, the best PR regimen remains to be defined.

Methods

The study compared the incidence and severity of IAR related to ATG according to the different PR therapy. This descriptive retrospective cohort study included patients receiving ATG in two HSCT transplant centers (Hospitals A and B). The data cut-off was in March 2020, but the period of interest was different between the two hospitals to balance the two groups. Four PR regimens were compared, one from Hospital A (PR-A) and three from Hospital B (PR-B1, B2, and B3), which have changed twice in the last decade. Along with PR therapy, the indication and method of administration of ATG also differed between hospitals.

Results

A total of 132 patients were included from May 2011 to March 2020. Groups PR-A, B1, B2, and B3 had, respectively, 61, 22, 26, and 23 patients. Of them, 115 (87 %) had at least one IAR, and 86 (65 %) had at least one severe IAR during any ATG infusions. ATG3 had the lowest incidence of IAR (39 %), and it seemed better tolerated when given after graft infusion than before (32 % vs. 46 %, respectively; p = 0.11). Almost three-quarters of patients had at least one IAR that occurred after the end of an ATG infusion, but there was less IAR with PR-B3 protocol where acetaminophen and diphenhydramine were regularly administered beyond ATG infusion. Hospital A used a progressive rate of infusion, but early IAR was seen compared to Hospital B (p = 0.03), where a fixed rate was used. No direct association was found between the CS dose received and IAR incidence (p = 0.21) or severity (p = 0.61). However, there was a recurrent signal for less severe IAR in the PR-B3 group compared to its predecessors, B1 and B2 groups (p = 0.12), and the key difference was an increased CS dose. The mean total CS therapy received was nearly double at Hospital A compared with Hospital B (1182 vs. 692 mg prednisone equivalent; p < 0.01). Fungal infection rate was higher in Hospital A compared to Hospital B (33 % vs. 13 %; p < 0.01). The infection rate correlated with a higher dose of CS received on days of ATG therapy (p < 0.01).

Conclusion

ATG3 given the day after HSCT appears to play a key role in reducing the incidence and severity of IAR. Infusion over six hours at a fixed rate was safe. Frequent, regular, and extended doses of acetaminophen and antihistamines beyond ATG infusion appear useful. Increasing CS doses led to IAR reduction, but this correlated with an increased infection rate.