Higher tacrolimus concentrations early after transplant reduce the risk of acute GvHD in reduced-intensity allogeneic stem cell transplantation.
Higher tacrolimus concentrations early after transplant reduce the risk of acute GvHD in reduced-intensity allogeneic stem cell transplantation.
复制标题
移植后较高的克莫司浓度降低了强度同种异体干细胞移植中急性GVHD的风险。
DOI：
10.1038/bmt.2015.323
复制
发表时间：
2016-04
影响因子：
4.8
通讯作者：
Reshef R
中科院分区：
文献类型：
--
作者：
Ganetsky A;Shah A;Miano TA;Hwang WT;He J;Loren AW;Hexner EO;Frey NV;Porter DL;Reshef R
由于药物相互作用和基因组变异，移植后早期他克莫司的血清浓度存在显着差异。我们对 120 名连续同种异体移植患者采用统一的降低强度预处理方案，评估了移植后早期他克莫司浓度是否与急性移植物抗宿主病的发生率相关。所有患者均接受口服他克莫司和静脉注射甲氨蝶呤的标准预防治疗。主要感兴趣的变量是移植后最初 4 周内他克莫司的平均每周浓度。在多变量分析中，第 1 周他克莫司浓度是急性 2 – 4 级移植物抗宿主病的独立预测因子（HR，0.90；95% CI，0.84 至 0.97；P < 0.01）。这种关联是由于第 1 周他克莫司浓度 >12 ng/mL 的患者发生急性 2 – 4 级移植物抗宿主病的风险较低（HR .47；95% CI，0.25 – .88；P = .02）。第 1 周他克莫司浓度与慢性移植物抗宿主病、复发或总生存期无关。第 2、3 和 4 周时较低的他克莫司浓度与较高的移植物抗宿主病发生率无关。总之，我们发现同种异体移植后第一周内较高的他克莫司浓度与强度降低的预处理方案与显着降低急性2-4级移植物抗宿主病的风险相关，并且不会增加复发风险。
There is significant variability in the serum concentrations of tacrolimus attained early post-transplant due to drug interactions and genomic variation. We evaluated whether tacrolimus concentrations early post-transplant correlate with incidence of acute graft-versus-host disease in 120 consecutive patients allografted with a uniform reduced-intensity conditioning regimen. All patients received standard prophylaxis with oral tacrolimus and intravenous methotrexate. The primary variable of interest was mean weekly tacrolimus concentrations in the initial 4 weeks post-transplant. In multivariate analysis, week 1 tacrolimus concentration was an independent predictor of acute grade 2 – 4 graft-versus-host disease (HR, .90; 95% CI, .84 to .97; P < .01). This association was driven by a lower risk of acute grade 2 – 4 graft-versus-host disease in patients with week 1 tacrolimus concentrations >12 ng/mL (HR .47; 95% CI, .25 – .88; P = .02). Week 1 tacrolimus concentrations were not associated with chronic graft-versus-host disease, relapse, or overall survival. Lower tacrolimus concentrations at weeks 2, 3, and 4 were not associated with a higher incidence of graft-versus-host disease. In summary, we found that higher tacrolimus concentrations during the first week after allografting with a reduced-intensity conditioning regimen were associated with significantly reduced risk of acute grade 2 – 4 graft-versus-host disease without increasing risk of relapse.
登录
查看更多内容
同种异体造血细胞移植后钙调神经磷酸酶抑制剂的血液浓度与结局之间的关联。
影响因子：
4.3
作者：
Ram, Ron;Storer, Barry;Mielcarek, Marco;Sandmaier, Brenda M.;Maloney, David G.;Martin, Paul J.;Flowers, Mary E. D.;Chua, Bee K.;Rotta, Marcello;Storb, Rainer
通讯作者：
Storb, Rainer
影响因子：
2.1
作者：
Johnston, Laura
通讯作者：
Johnston, Laura
影响因子：
20.3
作者：
Armand, Philippe;Kim, Haesook T.;Saber, Wael
通讯作者：
Saber, Wael
影响因子：
45.3
作者：
Eapen, Mary;Logan, Brent R.;Champlin, Richard E.
通讯作者：
Champlin, Richard E.
影响因子：
20.3
作者：
Sun, K;Wilkins, DEC;Murphy, WJ
通讯作者：
Murphy, WJ