Department of Hematology and Oncology, JA Aichi Konan Kosei Hospital, 137, Omatsubara, Takaya-cho, Konan, Aichi, 483-8704, Japan.
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
Int J Hematol. 2021 Jan;113(1):63-72. doi: 10.1007/s12185-020-02986-8. Epub 2020 Sep 2.
Tacrolimus (TAC) is essential for prophylaxis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (allo-HSCT). We have sometimes observed large fluctuations in TAC concentration. However, links between the variability in the concentration or the concentration/dose (C/D) ratio of TAC and clinical complications remain ambiguous. To clarify relationships between various parameters of TAC and early complications such as pre-engraftment immune reactions/engraftment syndrome, aGVHD, and transplant-associated thrombotic microangiopathy (TA-TMA), a total of 146 patients who underwent allo-HSCT were included. Intrapatient variabilities in the concentration and C/D ratio of TAC were estimated by intrapatient mean absolute deviation (iMAD). The mean concentration and C/D ratio of TAC were not significantly different between with and without complications. A strong association was observed between greater iMAD for TAC C/D ratio from days 15 to 21 and the development of TA-TMA. iMAD values for TAC C/D ratio of 11.4 or greater was a risk factor for TA-TMA and the cumulative incidence of nonrelapse mortality (NRM) was significantly higher in patients with iMAD values for TAC C/D ratio of 11.4 or greater. Intrapatient variability in the C/D ratio of TAC was associated with the incidence of TA-TMA and NRM and might be useful for predicting TA-TMA.
他克莫司（TAC）是预防异基因造血细胞移植（allo-HSCT）后急性移植物抗宿主病（aGVHD）所必需的。我们有时会观察到 TAC 浓度的大幅波动。然而，TAC 浓度或浓度/剂量（C/D）比值的变化与临床并发症之间的联系仍不清楚。为了阐明 TAC 的各种参数与早期并发症（如植入前免疫反应/植入综合征、aGVHD 和移植相关血栓性微血管病（TA-TMA））之间的关系，共纳入了 146 例接受 allo-HSCT 的患者。通过个体内平均绝对偏差（iMAD）来估计 TAC 浓度和 C/D 比值的个体内变异性。有并发症和无并发症患者的 TAC 平均浓度和 C/D 比值无显著差异。TAC C/D 比值从第 15 天到第 21 天的 iMAD 与 TA-TMA 的发生呈强相关性。TAC C/D 比值的 iMAD 值为 11.4 或更高是 TA-TMA 的危险因素，且 TAC C/D 比值的 iMAD 值为 11.4 或更高的患者累积无复发生存率（NRM）显著更高。TAC C/D 比值的个体内变异性与 TA-TMA 和 NRM 的发生有关，可能有助于预测 TA-TMA。
