Barkholt L, Remberger M, Bodegård H, Ringdén O, Böttiger Y
Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
Bone Marrow Transplant. 2007 Oct;40(7):683-9. doi: 10.1038/sj.bmt.1705788. Epub 2007 Jul 30.
Cyclosporine A (CsA) therapy based on 2-h concentrations (C2) after oral administration has demonstrated low acute rejection rates after solid organ transplantation. We analysed the correlation between C2 and trough (C0) levels of oral CsA therapy in samples obtained twice in consecutive weeks from 58 patients during their first admission for allogeneic haematopoietic stem cell transplantation. Also 8-h concentration curves were obtained from 23 patients. The mean (range) CsA dose was 332 (167-763) and 255 (113-575) mg/day for patients with matched unrelated donor (MUD) and human leukocyte antigen identical sibling donor (Sib), respectively. Median (range) C0 and C2 were 254 (145-332) and 898 (419-1466) ng/ml in MUD patients, and 130 (93-265) and 554 (196-988) ng/ml in Sib patients. In MUD patients with either aGVHD grade < II or > or = II, the median C2 were 915 (419-1466) and 890 (519-1399) ng/ml, respectively. In Sib patients with aGVHD grade < II or grade > or = II, the median C2 were 552 (404-718) and 539 (196-988) ng/ml, respectively. The median C2 levels were comparable in patients with or without severe infections. Interindividual variations in CsA uptake and metabolism may explain the wide variation of C2 levels without prediction for increased risk for severe aGVHD or infectious complication when C0 guided the CsA dosing.
基于口服给药后2小时浓度（C2）的环孢素A（CsA）治疗已显示出实体器官移植后较低的急性排斥率。我们分析了58例患者在首次接受异基因造血干细胞移植入院期间连续两周采集的样本中口服CsA治疗的C2与谷浓度（C0）水平之间的相关性。此外，还获得了23例患者的8小时浓度曲线。匹配无关供体（MUD）和人类白细胞抗原相同同胞供体（Sib）的患者，CsA平均（范围）剂量分别为332（167 - 763）和255（113 - 575）mg/天。MUD患者中，C0和C2的中位数（范围）分别为254（145 - 332）和898（419 - 1466）ng/ml，Sib患者中分别为130（93 - 265）和554（196 - 988）ng/ml。在aGVHD分级< II级或≥ II级的MUD患者中，C2中位数分别为915（419 - 1466）和890（519 - 1399）ng/ml。在aGVHD分级< II级或≥ II级的Sib患者中，C2中位数分别为552（404 - 718）和539（196 - 988）ng/ml。有或无严重感染的患者C2中位数水平相当。CsA吸收和代谢的个体差异可能解释了C2水平的广泛差异，且当以C0指导CsA给药时，无法预测严重aGVHD或感染并发症风险增加。
