Administration of Rabbit Anti-Thymocyte Globulin: Slowing Infusion Rate over a 4 Day Course with Aggressive Use of Pre-Medications May Decrease ATG Related Infusion Reactions

Anti-thymocyte globulin (ATG) during conditioning for allogeneic HSCT is often accompanied by infusion reactions; however, optimal methods to reduce these reactions have yet to be established. We report our experience with a modified infusion approach.

Between Nov 2010 and June 2013, 24 patients received rabbit ATG for MUD allo-HSCT at our institution. From Nov 2010 - Oct 2012 14 patients received protocol A with 2 mg/kg ATG on days -4, -3, and -2 via titrated infusion over 4+ hrs with methylprednisolone 60 mg IV and diphenhydramine 50 mg PO prior to each ATG dose. From Oct 2012 - June 2013, 10 patients received protocol B whereby ATG was over four days (1 mg/kg on day -5 and -2, 2 mg/kg on days -4 and -3) at fixed rate over 20 hrs with no change to premedication; however, additional diphenhydramine and famotidine were given around the clock. For all patients, if ATG was held resulting in wasting of partial dose, additional ATG was given to complete total dose prescribed.

Over the course of ATG, the number of times the ATG infusion was held due to an infusion reaction was higher for protocol A (12 times for 14 patients) than protocol B (7 times for 10 patients). For the 14 patients on protocol A, 64% had ATG held on day 1, 7% on day 2, and 14% on day 3. For the 10 patients on protocol B, 20% had ATG held on day 1, 10% on day 2, and 20% on days 3 and 4, respectively. Although the percent of patients experiencing fever, rigors, or tachycardia appeared to be lower for protocol B on the first two days of ATG, this was not consistent for alterations in blood pressure or for the third day of ATG infusion.

For each ATG day, additional doses of steroid were required in more patients on protocol A vs. B (day one: 8 vs. 0; day two: 2 vs. 0; day three: 5 vs. 1; day four: n/a vs. 0). The median amount of additional steroid (in mg of methylprednisolone equivalents) necessary in protocol A was 40 mg (range 20-145) for the 8 patients treated on day one, 48 mg (range 32-100) for the 3 patients on day two, and 80 mg (range 30-125) for the 5 patients on day three. For protocol B, only 1 patient required 30 mg of methylprednisolone on day three.

No difference was noted in the number of patients who required an additional amount of ATG to complete the regimen (3/14 vs. 2/10). However, for protocol A the amount of ATG administered on an additional day to complete the regimen ranged from 11-33% of total ATG dose whereas for protocol B the amount was 2.5-11% with one patient having the amount added to the last day of scheduled ATG. Importantly, all patients successfully received the full amount of ATG. No difference in time to engraftment was noted between groups.

This pilot data suggests slowing the infusion rate and spreading the total ATG dose over 4 days with aggressive use of antihistamine pre-medications has the potential to decrease infusion reactions and need for additional steroid doses.  Additional patients on protocol B are being added and results including long-term outcomes will be updated.