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

International Journal of Hematology(2022)

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摘要
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.
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关键词
Haploidentical hematopoietic stem cell transplantation, Pharmacokinetics, ATG, GVHD, Concentration
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