Association between the pharmacokinetics of rabbit anti-thymocyte globulin and acute graft-versus-host disease in patients who received haploidentical hematopoietic stem cell transplantation.

Anti-thymocyte globulin (ATG) is an important prophylactic drug against acute graft-versus-host disease (aGVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). This study analyzed the pharmacokinetics of rabbit ATG 2.5 mg/kg and its effect against aGVHD in 24 patients undergoing unmanipulated haplo-HSCT. All patients had hematological malignancies not in remission. The median absolute lymphocyte count (ALC) before rabbit ATG administration was 9.5/µL (range 0-41/µL). The grade ≥ II aGVHD group had a significantly lower median rabbit ATG concentration on days 0 (C ₀ ) and 7 (C ₇ ) and areas under the curve on days 0-7 (AUC _0-7 ) and 0-32 (AUC _0-32 ) than the grade 0-I aGVHD group. Among the four parameters, C ₀ was the most optimal for predicting aGVHD according to the receiver-operating characteristic (ROC) analysis (area under the ROC curve 0.893; 95% confidence interval 0.738-1.000). The high C ₀ (≥ 27.8 µg/mL) group had significantly lower cumulative incidence of grade ≥ II aGVHD on day 100 than the low C ₀ (< 27.8 µg/mL) group (13.8% vs. 88.9%, p < 0.001). In haplo-HSCT, the C ₀ of rabbit ATG is a good predictor of grade ≥ II aGVHD, even though ALC before rabbit ATG administration is not a predictor of aGVHD.
(© 2022. Japanese Society of Hematology.)