Differences of Antithymocyte Globulin (ATG) Side Effects during Allogeneic Stem Cell Transplantation

Introduction: Due to its production and mechanism of action, antithymocyte globulin (ATG) is associated with two main side effects: immunological responses and infections.

Objective: We evaluate the incidence and differences of ATG infusion reactions and fungal and viral infections in patients who receive SCT across a period of 10 years.

Patients and methods: From January 2005 to December 2014, 100 patients who underwent and allogeneic stem cell transplantation (SCT) in our center received ATG (Thymoglobulin [TG] or ATG-Fresenius [ATG-F]) as part of conditioning regimen. Because an out of trend had been noted in stability profiling of TG finished product lots manufactured since December 2009 and since July 2012, TG was switched by ATG-F, patients were divided into three groups (TG-1: 45 patients; TG-2: 31 patients; ATG-F: 24 patients). Total median dose of TG was 7.5 mg/Kg in both groups.

Results: Patients transplanted with ATG-F were significantly older than those who received TG (p=0.009). In addition, the use of an unrelated donor and GVHD prophylaxis with calcineurin inhibitor combined with mycophenolate mofetil was more frequent in ATG-F group (p=0.04 and p <0.0001 respectively). There were no differences between the groups in the underlying disease and its status at the transplant, the intensity of the conditioning regimen and the recipient/donor CMV and EBV serology. The majority of patients engrafted (93.3%, 93.5% and 95.8%) and neutrophil and platelet recovery was similar between three groups. Although there were no statistical differences, TG-2 showed less acute and chronic GVHD compared with TG-1 and ATG-F. All patients received premedication with corticoids. In all groups, pyrexia and chills were the most frequent symptom associated with ATG administration. All patients in TG-2 group showed infusion reaction (p= 0.006) and compared with TG-1 and ATG-F, they presented more peripheral edema (p=0.003), diarrhea (p=0.001), pulmonary edema (p=0.002) and dyspnea (p=0.005).

Fungal infection was more frequent in TG-1 (30.2% vs 13.3% and 4.3%,p=0.024). CMV reactivation and BK viruria was more frequent in ATG-F (p=0.048 and 0.005, respectively). In contrast, EBV reactivation and Post Transplant Lymphoproliferative Disorder (PTLD) was more frequent in TG-2 group (33.3% vs 2.6% and 16.7%, p=0.003 and 25.8% vs 0% and 4.2%, p<0.0001, respectively).

Conclusion

During ATG infusion, pyrexia and chills are the most common side in SCT. The screening and prophylaxis of fungal infections may be associated with the diminishing of the incidence of this complication during the studied period. The use of older patients and the mycophenolate may be associated with an increasing incidence of CMV reactivation. By contrast, it is unclear if the out of trend noted in stability profiling of TG finished product lots manufactured since December 2009 has had influence in the type of infusion reactions and the incidence of EBV reactivations and PTLD observed in the TG-2 group.