Longitudinal assessment of morbidity and acute graft-versus-host disease after allogeneic hematopoietic cell transplantation: retrospective analysis of a multicenter phase III study.
Longitudinal assessment of morbidity and acute graft-versus-host disease after allogeneic hematopoietic cell transplantation: retrospective analysis of a multicenter phase III study.
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DOI：
10.1016/j.bbmt.2009.03.009
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发表时间：
2009-06
影响因子：
4.3
通讯作者：
Nash, Richard A.
中科院分区：
文献类型：
--
作者：
Carnevale-Schianca, Fabrizio;Leisenring, Wendy;Martin, Paul J.;Furlong, Terry;Schoch, Gary;Anasetti, Claudio;Appelbaum, Frederick R.;Carpenter, Paul A.;Deeg, H. Joachim;Kiem, Hans-Peter;Storb, Rainer;McDonald, George B.;Nash, Richard A.
由于HCT后早期的发病率在很大程度上是由于急性GVHD的发生，我们先前提出，对涉及皮肤、肝脏和胃肠道的发病率进行纵向评估，可能为比较两组急性GVHD预防的开放标签随机临床试验提供更完整、客观的方法。在本研究中，我们对一项开放标签随机临床试验的数据库进行了回顾性分析，比较了他克莫司/甲氨蝶呤与环孢素/甲氨蝶呤在清髓性预处理和HLA匹配的无关供体骨髓移植后的发病率和GVHD。结果证实，与0-I级GVHD患者相比，II-IV级GVHD峰值患者的总体发病率随时间推移存在差异，但与0-I级GVHD相比，II级GVHD相关的发病率无显著差异。我们观察到他克莫司组随着时间的推移，（p=0.04; p= 0.09），但不包括胃肠道或总体发病率，尽管他克莫司组中皮肤和肝脏分期以及GVHD总体分级随时间显著降低。在急性GVHD预防的随机临床试验中，作为急性GVHD的量度，对发病率差异（无论原因如何）的客观评估具有有限的效用。从客观参数（如生存率和发病率）证明临床获益的难度以及急性GVHD分级的主观性强调了在GVHD预防的临床试验中需要进行盲法评估。
Since morbidity early after HCT results in large part from the development of acute GVHD, we previously proposed that a longitudinal assessment of morbidity involving the skin, liver, and gastrointestinal tract might provide a more complete, objective approach for comparing two arms of open-label randomized clinical trials for acute GVHD prevention. In the current study, we determined both morbidity-across-time and GVHD-across-time in a retrospective analysis of a database from an open-label randomized clinical trial comparing tacrolimus/methotrexate versus cyclosporine/methotrexate after myeloablative conditioning and marrow transplantation from HLA-matched unrelated donors. The results confirmed differences in overall morbidity across time among patients with peak grades II-IV GVHD as compared to those with grades 0-I GVHD, but no significant differences were found between morbidity associated with grade II GVHD as compared to grades 0-I GVHD. We observed less skin and a trend towards less liver morbidity across time in the tacrolimus group (p=0.04; p= 0.09, respectively) but not for gastrointestinal or overall morbidity, despite significantly decreased skin and liver stages and overall grades of GVHD-across-time in the tacrolimus arm. In conclusion, an objective assessment of differences in morbidity (regardless of cause) as a measure of acute GVHD in a randomized clinical tria of acute GVHD prevention had limited utility. The difficulty of demonstrating clinical benefits from objective parameters such as survival and morbidity and the subjectivity of grading acute GVHD emphasize that blinded assessments are required in clinical trials of GVHD prevention.
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影响因子：
4.8
作者：
Martin, P;Nash, R;Appelbaum, F
通讯作者：
Appelbaum, F
影响因子：
168.9
作者：
Wagner, JE;Thompson, JS;Kernan, NA
通讯作者：
Kernan, NA
影响因子：
20.3
作者：
Leisenring, Wendy M.;Martin, Paul J.;McDonald, George B.
通讯作者：
McDonald, George B.
影响因子：
6.2
作者：
GLUCKSBERG, H;STORB, R;THOMAS, ED
通讯作者：
THOMAS, ED
影响因子：
6.5
作者：
Al-Ghamdi, H;Leisenring, W;Martin, PJ
通讯作者：
Martin, PJ