Clinicoprognostic implications of increased serum levels of vascular endothelial growth factor and basic fibroblastic growth factor in early B-cell chronic lymphocytic leukaemia
Clinicoprognostic implications of increased serum levels of vascular endothelial growth factor and basic fibroblastic growth factor in early B-cell chronic lymphocytic leukaemia
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DOI：
10.1038/sj.bjc.6600022
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发表时间：
2002-01-07
影响因子：
8.8
通讯作者：
Digiesi, G
中科院分区：
文献类型：
--
作者：
Molica, S;Vitelli, G;Digiesi, G
为了评估血管内皮生长因子和碱性成纤维细胞生长因子血清水平升高在预测早期B细胞慢性淋巴细胞白血病患者疾病进展风险方面的相对价值，我们分析了81名Binet A期患者，这些患者在诊断时采集血清，并使用酶联免疫吸附试验（ELISA）评估血管内皮生长因子和碱性成纤维细胞生长因子的存在。连接免疫吸附测定血清血管内皮生长因子水平与Rai分期（P=0.03）、外周血淋巴细胞增多（P=0.03）、骨髓组织学（P=0.04）和β 2-微球蛋白（β 2-m）（P=0.006）呈正相关。当处理碱性成纤维细胞生长因子时，仅发现与Rai亚阶段的相关性（P=0.02）。基于四分位数分层设置的不同截止值未能证明碱性成纤维细胞生长因子的血清水平与疾病进展之间的任何相关性。相比之下，血清血管内皮生长因子水平升高（高于中位数，203 pg ml（-1））的患者疾病进展的风险增加了3倍，尽管在多变量分析中，只有Rai分期（P=0.0001）和淋巴细胞倍增时间（P=0.002）保留了其预后意义。低水平的血管内皮生长因子表明低（P=0.02）或高（P=0.03）β 2-m浓度患者亚组的临床结局良好。最后，当血清血管内皮生长因子和β 2-m联合检测时，获得了最高的预后能力。血清血管内皮生长因子和β 2-m均高于中位值的患者的中位无进展生存期仅为13个月，相比之下，一种标志物升高（即高于第50百分位数）的患者的中位无进展生存期为40个月。两种标志物均低于中位数的患者的临床结局最好（40个月时未达到中位无进展生存期）。总之，早期慢性淋巴细胞白血病患者的血管内皮生长因子或碱性成纤维细胞生长因子的血清水平较高，然而，只有血管内皮生长因子预测疾病的行为，并有助于改善A期患者的预后。
To assess the relative merit of increased serum levels of vascular endothelial growth factor and basic fibroblastic growth factor in predicting the risk of disease progression of patients with early B-cell chronic lymphocytic leukaemia we analyzed 81 Binet stage A patients whose sera were taken at the time of diagnosis and evaluated for the presence of vascular endothelial growth factor and basic fibroblast growth factor using an enzyme-linked immunosorbent assay. Serum levels of vascular endothelial growth factor positively correlated with Rai sub-stages (P=0.03), peripheral blood lymphocytosis (P=0.03), bone marrow histology (P=0.04) and beta2-microglobulin (beta2-m) (P=0.006). When dealing with basic fibroblast growth factor only a correlation with Rai sub-stages (P=0.02) could be found, Different cut-offs set on the basis of a stratification in quartiles, failed to demonstrate any correlation between serum levels of basic fibroblast growth factor and disease progression. In contrast, patients with increased serum levels of vascular endothelial growth factor (above median value, 203 pg ml(-1)) had a three times increased risk of disease progression, although, in multivariate analysis only Rai sub-stages (P=0.0001) and lymphocyte doubling time (P=0.002) retained their prognostic significance. Low levels of vascular endothelial growth factor were indicative of good clinical outcome in the subgroup of patients with either low (P=0.02) or high (P=0.03) beta2-m concentration. Finally, the highest prognostic power was obtained when serum vascular endothelial growth factor and beta2-m were examined in combination. Median of progression-free survival of patients who had both serum vascular endothelial growth factor and beta2-m higher than median value was only 13 months, in contrast median progression-free survival of patients with one marker increased (i.e. above the 50th percentile) was 40 months. Patients with both markers below the median experienced the best clinical outcome (median progression-free survival not reached at 40 months). In conclusion, serum levels of either vascular endothelial growth factor or basic fibroblast growth factor are high in patients with early chronic lymphocytic leukaemia, however, only vascular endothelial growth factor predicts behaviour of disease and helps to refine the prognosis of stage A patients.