Determining the Optimal Anti-Thymocyte Globulin Exposure in Haploidentical Peripheral Blood Stem Cell Transplantation

By Patrick Daly - Last Updated: March 24, 2022

Anti-thymocyte globulin (ATG) is used in conditioning prior to allogeneic hematopoietic stem cell transplantation for acute graft-versus-host disease (aGVHD) prophylaxis—however, ATG was shown to increase virus reactivation after transplantation. Researchers, led by HaiTao Wang, conducted a prospective study to identify an optimal ATG exposure that “ensures engraftment, effectively prevents aGVHD, and reduces the risk of virus reactivation without increasing relapse of malignant diseases.” Their study, published in Transplantation and Cellular Therapy, advanced their findings in support of an “optimal active ATG exposure of 110–148.5 UE/ml per day.”

The prospective study enrolled a total of 106 patients with hematological malignancies who received a first-time haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with 10 mg/kg rabbit-ATG (thymoglobulin) administered on the fifth through the second days prior to transplantation. The primary measures of the study were the areas under the concentration-time curve (AUCs) of total, pre-, and post-transplant active ATG.

According to the article, the AUC of total active ATG was the strongest predictor for virus reactivation and onset of grade II to IV aGVHD. The optimal total AUC range of active ATG was shown to be 100–148.5 UE/ml per day. The median time to myeloid engraftment was 14 days for patients who received the optimal AUC range, compared to 13 days for patients who received non-optimal AUC (p = 0.184). Additionally, median time to platelet engraftment was 13 days in both the optimal and non-optimal AUC groups (p = 0.263). Patients with optimal AUC had a lower cumulative incidence (CI) of cytomegalovirus (CMV) reactivation (60.6% [95% confidence interval (CI), 21.2–45.3%] vs. 77.1% [95% CI, 64.5–87.7%]; p = 0.016) and persistent CMV viremia (31.5% [95% CI, 21.2–45.3%] vs. 56.3% [95% CI, 42.9–70.4%]; p = 0.007) than patients with non-optimal AUC. Likewise, the CI of persistent Epstein-Barr virus (EBV) viremia was significantly lower in the optimal AUC group versus the non-optimal group (33.1% [95% CI, 22.5–46.8%] vs. 52.6% [95% CI, 39.3–67.2%] p = 0.048); However, the authors found no difference between the groups in the rate of EBV reactivation (p = 0.752). Both groups demonstrated similar rates of grade II–IV and grade III–IV aGVHD (48.6% [95% CI, 36.8–62.0%] vs. 37.0% [95% CI, 24.8–52.5%]; p = 0.113; and 10.4% [95% CI, 4.8–21.7%] versus 4.2% [95% CI, 1.0–15.6%]; p = 0.234, respectively).

Lastly, though relapse, non-relapse mortality, and disease-free survival were not significantly different between the groups, two-year overall survival “tended to increase in optimal AUC group,” according to the authors (p = 0.061). Altogether, the study’s contributors proposed an optimal range of ATG exposure, and ultimately suggested their study indicated that “Individualized dosing of ATG in allo-HCT might reduce the risk of virus reactivation and effectively prevent aGVHD simultaneously”