NOTCH1, SF3B1, and TP53 mutations in fludarabine-refractory CLL patients treated with alemtuzumab: results from the CLL2H trial of the GCLLSG
NOTCH1, SF3B1, and TP53 mutations in fludarabine-refractory CLL patients treated with alemtuzumab: results from the CLL2H trial of the GCLLSG
复制标题
DOI：
10.1182/blood-2013-03-488197
复制
发表时间：
2013-08-15
期刊：
影响因子：
20.3
通讯作者：
Stilgenbauer, Stephan
中科院分区：
文献类型：
--
作者：
Schnaiter, Andrea;Paschka, Peter;Stilgenbauer, Stephan
在CLL2H试验中，我们研究了NOTCH1和SF3B1突变(NOTCH1（mut), SF3B1(mut)）与TP53（mut）在阿仑单抗治疗的氟达拉滨难治性慢性淋巴细胞白血病（CLL）患者中的发病率，相关性和预后作用。我们分别在13.4%、17.5%和37.4%的患者中发现NOTCH1（mut）、SF3B1（mut）和TP53（mut）。NOTCH1（mut）和SF3B1（mut）相互排斥，而TP53（mut）在两个亚组中均匀分布。除了SF3B1（mut）与11q缺失相关（P 5.029）外，突变与任何基线特征或应答率没有其他显著关联。然而，与野生型病例相比，NOTCH1（mut）病例的无进展生存期（PFS）明显更长（15.47个月vs 6.74个月；P = 0.025），尽管总生存期（OS）没有显著差异。SF3B1（mut）对PFS和OS无显著影响。在多变量分析中，NOTCH1（mut）被确定为PFS的独立有利标记。该临床试验在www.clinicaltrials.gov注册，编号为#NCT00274976。
We studied the incidences, associations, and prognostic roles of NOTCH1 and SF3B1 mutations (NOTCH1(mut), SF3B1(mut)) as compared with TP53(mut) in fludarabine-refractory chronic lymphocytic leukemia (CLL) patients treated with alemtuzumab in the CLL2H trial. We found NOTCH1(mut), SF3B1(mut), and TP53(mut) in 13.4%, 17.5%, and 37.4% of patients, respectively. NOTCH1(mut) and SF3B1(mut) weremutually exclusive, whereas TP53(mut) were evenly distributed within both subgroups. Apart from correlation of SF3B1(mut) with 11q deletion (P 5.029), there were no other significant associations of the mutations with any baseline characteristics or response rates. However, NOTCH1(mut) cases had a significantly longer progression-free survival (PFS) compared with wild-type cases (15.47 vs 6.74 months; P = .025), although there was no significant difference with overall survival (OS). SF3B1(mut) had no significant impact on PFS and OS. In multivariable analyses, NOTCH1(mut) was identified as an independent favorable marker for PFS. This clinical trial is registered at www.clinicaltrials.gov as #NCT00274976.