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

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作者
Masahiro Teramoto
Satoshi Maruyama
Hiroya Tamaki
Katsuji Kaida
Azusa Mayumi
Keiko Fukunaga
Takayuki Inoue
Kyoko Yoshihara
Satoshi Yoshihara
Kazuhiro Ikegame
Masaya Okada
Yuko Osugi
Hiroyasu Ogawa
Satoshi Higasa
Kunihiko Morita
Kana Matsumoto
Takashi Kijima
机构
[1] Hyogo College of Medicine,Department of Respiratory Medicine and Hematology
[2] Chiba Cancer Center,Department of Hematology
[3] Kyoto Prefectural University of Medicine,Oncology
[4] Hyogo College of Medicine,Department of Pediatrics
[5] Doshisha Women’s College of Liberal Arts,Department of Transfusion Medicine and Cell Therapy
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关键词
Haploidentical hematopoietic stem cell transplantation; Pharmacokinetics; ATG; GVHD; Concentration;
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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 (C0) and 7 (C7) and areas under the curve on days 0–7 (AUC0–7) and 0–32 (AUC0–32) than the grade 0–I aGVHD group. Among the four parameters, C0 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 C0 (≥ 27.8 µg/mL) group had significantly lower cumulative incidence of grade ≥ II aGVHD on day 100 than the low C0 (< 27.8 µg/mL) group (13.8% vs. 88.9%, p < 0.001). In haplo-HSCT, the C0 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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页码:248 / 257
页数:9
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