Baff serum level predicts time to first treatment in early chronic lymphocytic leukemia
Baff serum level predicts time to first treatment in early chronic lymphocytic leukemia
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DOI：
10.1111/j.1600-0609.2010.01482.x
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发表时间：
2010-10-01
影响因子：
3.1
通讯作者：
Ferrarini, Manlio
中科院分区：
文献类型：
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作者：
Molica, Stefano;Digiesi, Giovanna;Ferrarini, Manlio
我们分析了 B 细胞慢性淋巴细胞白血病 (CLL) 中已确立的与预后相关的生物学参数之间的相关性 [即免疫球蛋白重链可变区 (IgVH)、ZAP-70 和 CD38 表达的突变状态]和 B 细胞激活因子（TNF 家族的 BAFF）的血清水平，通过评估这些变量对 169 名 Binet A 期既往未治疗的 CLL 患者的首次治疗时间 (TFT) 的影响。较高水平的 BAFF 更常见与女性性别 (P = 0.02)、年轻年龄 (P = 0.01），Rai 0 期（P = 0.002），较高的血小板计数（P = 0.005），突变的 IgVH 疾病（P = 0.002），正常细胞遗传学特征或存在 13q 缺失的发生率较高（P = 0.02），低 ZAP-70-（P = 0.003）和 CD38 表达（P = 0.02）。最大选择对数秩统计图确定血清 BAFF 浓度 0.313 ng/mL 为最佳截止值 (P < 0.0001)。该阈值识别出具有不同 TFT 的两个患者子集 (P < 0.0001)。因为在多变量分析中可溶性BAFF[风险比(HR)，8.23；置信区间 (CI) 95%，3.0-22.6，P < 0.0001] 和 IgVH 突变状态（HR = 2.60；CI 95% 1.10-6.14，P = 0.03）保持了区分力，评估了它们对临床结果的综合影响。当考虑三组时：（1）低风险（n = 93）、IgVH（mut）一致且可溶性 BAFF 较高的患者； (2) 中危 (n = 50)，IgVH(mut) 和低 BAFF 水平或 IgVH(unmut) 和可溶性较高 BAFF 水平的患者；(3) 高危 (n = 26)，IgVH (unmut) 一致和低可溶性 BAFF 的患者，2 年 TFT 分别为 95%、85% 和 41% (P < 0.0001）。总之，我们的结果表明，在早期 B 细胞 CLL 中，包括可溶性 BAFF 在内的生物学特征可以为了解预后变量的复杂相互关系提供有用的见解。
We analyzed the correlation between well-established biological parameters of prognostic relevance in B-cell chronic lymphocytic leukemia (CLL) [i.e. mutational status of the immunoglobulin heavy chain variable region (IgVH), ZAP-70 and CD38 expression] and serum levels of B cell-activating factor (BAFF of the TNF family) by evaluating the impact of these variables on the time to first treatment (TFT) in a series of 169 previously untreated CLL patients in Binet stage A. Higher levels of BAFF were more frequently associated with female gender (P = 0.02), younger age (P = 0.01), Rai stage 0 (P = 0.002), higher platelet count (P = 0.005), mutated IgVH disease (P = 0.002), higher occurrence of normal cytogenetic profile or presence of 13q deletion (P = 0.02), low ZAP-70- (P = 0.003), and CD38-expression (P = 0.02). Maximally selected log-rank statistic plot identified a serum BAFF concentration of 0.313 ng/mL as the best cut-off (P < 0.0001). This threshold recognized two subsets of patients with different TFT (P < 0.0001). Because in multivariate analysis soluble BAFF [Hazard ratio (HR), 8.23; confidence Interval (CI) 95%,3.0-22.6, P < 0.0001] and mutational status of IgVH (HR = 2.60; CI 95% 1.10-6.14, P = 0.03) maintained the discriminating power their combined effect on clinical outcome was assessed. When three groups were considered: (1) low-risk (n = 93), patients with concordant IgVH(mut) and higher soluble BAFF; (2) intermediate-risk (n = 50), patients with IgVH(mut) and low BAFF levels or IgVH(unmut) and soluble higher BAFF;(3) high-risk (n = 26), patients with concordant IgVH (unmut) and low soluble BAFF, the 2-yr TFTs were, respectively, 95%, 85%, and 41% (P < 0.0001). In conclusion, our results indicate that in early B-cell CLL, the biological profile including among other parameters soluble BAFF may provide a useful insight into the complex interrelationship of prognostic variables.