Comprehensive assessment of prognostic factors predicting outcome in Chinese patients with chronic lymphocytic leukemia treated with fludarabine and cyclophosphamide
Comprehensive assessment of prognostic factors predicting outcome in Chinese patients with chronic lymphocytic leukemia treated with fludarabine and cyclophosphamide
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DOI：
10.1007/s12032-011-0054-2
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发表时间：
2012-09
期刊：
影响因子：
3.4
通讯作者：
Min Xu;L. Fan;K. Miao;Peng Liu;W. Xu;Jian-yong Li
中科院分区：
文献类型：
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作者：
Min Xu;L. Fan;K. Miao;Peng Liu;W. Xu;Jian-yong Li
为了确定预后因素是否仍然与氟达拉滨和环磷酰胺（FC）治疗的慢性淋巴细胞白血病（CLL）患者相关，我们前瞻性评估了86例接受FC一线治疗的中国CLL患者。24例患者（27.9%）达到完全缓解（CR），总有效率为75.6%。中位随访时间为41个月，中位无进展生存期（PFS）为36.0个月，中位总生存期（OS）尚未达到。单因素分析显示，晚期Binet分期、未突变IGHV、del（17 p13）或del（11 q23）细胞遗传学异常和p53突变与CR率较低密切相关。逐步logistic回归分析表明，未突变的IGHV和p53异常（p53缺失或突变）与实现CR的几率降低相关。治疗周期短、未达到CR、Binet分期晚期和p53异常与PFS缩短显著相关。此外，在多因素分析中，p53异常和先进的Binet分期被确定为早期复发的重要危险因素。未达到CR、Binet分期晚期、ZAP-70阳性和p53异常是决定OS的不利因素。多因素分析显示，只有p53异常与OS显著缩短独立相关。这些结果表明，p53异常的患者应考虑替代治疗。
To determine whether prognostic factors remain relevant to chronic lymphocytic leukemia (CLL) patients treated with fludarabine and cyclophosphamide (FC), we prospectively evaluated 86 Chinese CLL patients who received FC in first-line therapy. Twenty-four patients (27.9%) achieved complete remission (CR), and overall response rate was 75.6%. With a median follow-up of 41 months, the median progression-free survival (PFS) was 36.0 months and median overall survival (OS) has not been reached. The strong correlations of lower CR rate with advanced Binet stage, unmutated IGHV, cytogenetic abnormalities of del(17p13) or del(11q23), and p53 mutations were observed by univariable analyses. Stepwise logistic regression identified that unmutated IGHV and p53 abnormality (p53 deletion or mutation) were associated with a decreased odds of achieving CR. The less cycles of treatment, not achieving CR, advanced Binet stage, and p53 abnormality significantly correlated with a shortened PFS. Furthermore, in a multivariate analysis, p53 abnormality and advanced Binet stage were identified as being significant risk factors for early relapse. Not achieving CR, advanced Binet stage, ZAP-70-positive, and p53 abnormality were the adverse factors in determining OS. Only p53 aberration was independently associated with significantly shorter OS by a multivariate analysis. These results suggest that patients with p53 abnormality should be considered for alternative therapies.