Association between calcineurin inhibitor blood concentrations and outcomes after allogeneic hematopoietic cell transplantation.
Association between calcineurin inhibitor blood concentrations and outcomes after allogeneic hematopoietic cell transplantation.
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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。
DOI：
10.1016/j.bbmt.2011.08.016
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发表时间：
2012-03
影响因子：
4.3
通讯作者：
Storb, Rainer
中科院分区：
文献类型：
--
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
确定异基因造血细胞移植（HCT）后第一个月内钙调神经磷酸酶抑制剂（CNI）血药浓度是否与移植物抗宿主病（GVHD）的发生率和其他结局相关，我们回顾性分析了1181例血液系统恶性肿瘤患者的数据，这些患者的HCT来自HLA匹配的相关（n=634）或无关（n=547）2001年至2009年期间，一个机构的捐助者。清髓性HCT（n=774）后，较高的CNI浓度与急性或慢性GVHD的风险降低无关。在非清髓性HCT（n=407）后，较高的环孢素浓度与2-4级和3-4级急性GVHD风险降低相关（环孢素浓度每100 ng/ml变化的风险比[HR]，0.7; 95%置信区间[CI]，0.6-0.82;和HR，分别为0.66，95%CI，0.49-0.9）、非复发死亡率（HR，0.6，95%CI，0.41-0.88）和总死亡率（HR，0.83，95%CI，0.71-0.99）。环孢素浓度与非清髓性HCT后慢性GVHD和恶性肿瘤复发的风险无关。在非清髓性HCT后给予他克莫司的患者中，观察到CNI相关GVHD保护的相似趋势。较高的CNI浓度与明显的肾毒性无关。我们的结论是，较高的环孢素浓度相对较早的非清髓性HCT后提供保护急性GVHD，转化为非复发和总死亡率的风险降低。
To determine whether calcineurin inhibitor (CNI) blood concentrations within the first month after allogeneic hematopoietic cell transplantation (HCT) correlated with the incidence of graft-versus-host disease (GVHD) and other outcomes, we retrospectively analyzed data from 1181 patients with hematologic malignancies who had HCT from HLA-matched related (n=634) or unrelated (n=547) donors at a single institution between 2001 and 2009. After myeloablative HCT (n=774), higher CNI concentrations were not associated with lower risks of acute or chronic GVHD. After nonmyeloablative HCT (n=407), higher cyclosporine concentrations were associated with decreased risks of grade 2–4 and 3–4 acute GVHD (hazard ratio [HR] per 100 ng/ml change in cyclosporine concentrations, 0.7; 95% confidence interval [CI], 0.6–0.82; and HR, 0.66, 95%CI, 0.49–0.9, respectively), non-relapse mortality (HR, 0.6, 95% CI, 0.41–0.88), and overall mortality (HR, 0.83, 95%CI, 0.71–0.99). Cyclosporine concentrations were not associated with risks of chronic GVHD and recurrent malignancy after nonmyeloablative HCT. Among patients given tacrolimus after nonmyeloablative HCT, a similar trend of CNI-associated GVHD-protection was observed. Higher CNI concentrations were not associated with apparent renal toxicity. We conclude that higher cyclosporine concentrations relatively early after nonmyeloablative HCT confer protection against acute GVHD that translates into reduced risks of non-relapse and overall mortality.
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影响因子：
20.3
作者：
Hockenbery, David M.;Cruickshank, Scott;McDonald, George B.
通讯作者：
McDonald, George B.
影响因子：
20.3
作者：
Storb, R;Yu, C;Shulman, H
通讯作者：
Shulman, H
影响因子：
6.5
作者：
STOCKSCHLAEDER, M;STORB, R;WITHERSPOON, R
通讯作者：
WITHERSPOON, R
影响因子：
2.9
作者：
GHALIE, R;FITZSIMMONS, WE;KAIZER, H
通讯作者：
KAIZER, H
影响因子：
20.3
作者：
GRATWOHL, A;HERMANS, J;NIEDERWIESER, D
通讯作者：
NIEDERWIESER, D