Prospective evaluation of clonal evolution during long-term follow-up of patients with untreated early-stage chronic lymphocytic leukemia
Prospective evaluation of clonal evolution during long-term follow-up of patients with untreated early-stage chronic lymphocytic leukemia
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DOI：
10.1200/jco.2006.06.9492
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发表时间：
2006-10-01
影响因子：
45.3
通讯作者：
Dewald, Gordon W.
中科院分区：
文献类型：
--
作者：
Shanafelt, Tait D.;Witzig, Thomas E.;Dewald, Gordon W.
回顾性研究表明，间期荧光原位杂交（FISH）检测细胞遗传学异常可以识别慢性淋巴细胞白血病（CLL）患者，这些患者将经历更积极的病程。其他研究表明，患者可能在疾病过程中获得染色体异常。有最小的前瞻性数据的临床效用的广泛使用的分层FISH预后类别的患者与新诊断的早期CLL或克隆演变的频率由interphase FISH.Patients和MethodsBetween 1994年和2002年，我们招募了159例患者与以前未经治疗的CLL（83%Rai阶段0/1）的前瞻性试验评估克隆演变FISH。患者提供的基线和后续标本FISH检测在2至12 years. ResultsFISH检测到的染色体异常在研究进入预测总生存期。18例患者在随访期间发生克隆演变。克隆演变率随着随访时间的延长而增加，前2年仅发生1例（n = 71; 1.4%），但在5年以上后检测的患者中发生17例（n = 63; 27%）。克隆演变发生在10%的ZAP-70阴性和42%的ZAP-70阳性患者在5+ years（P =.008）.ConclusionThis临床试验证实了前瞻性的细胞遗传学异常检测FISH可以预测CLL患者的总生存率在诊断时，但也表明，许多患者获得新的异常在他们的疾病过程中。具有较高ZAP-70表达的患者可能更有可能经历这种克隆进化。这些发现对高危早期CLL患者的临床管理和早期治疗试验具有重要意义。
PurposeRetrospective studies suggest cytogenetic abnormalities detected by interphase fluorescent in situ hybridization (FISH) can identify patients with chronic lymphocytic leukemia (CLL) who will experience a more aggressive disease course. Other studies suggest that patients may acquire chromosome abnormalities during the course of their disease. There are minimal prospective data on the clinical utility of the widely used hierarchical FISH prognostic categories in patients with newly diagnosed early-stage CLL or the frequency of clonal evolution as determined by interphase FISH.Patients and MethodsBetween 1994 and 2002, we enrolled 159 patients with previously untreated CLL (83% Rai stage 0/1) on a prospective trial evaluating clonal evolution by FISH. Patients provided baseline and follow-up specimens for FISH testing during 2 to 12 years.ResultsChromosomal abnormalities detected by FISH at study entry predicted overall survival. Eighteen patients experienced clonal evolution during follow-up. The rate of clonal evolution increased with duration of follow-up with only one occurrence in the first 2 years (n = 71; 1.4%) but 17 occurrences (n = 63; 27%) among patients tested after 5+ years. Clonal evolution occurred among 10% of ZAP-70-negative and 42% of ZAP-70-positive patients at 5+ years (P =.008).ConclusionThis clinical trial confirms prospectively that cytogenetic abnormalities detected by FISH can predict overall survival for CLL patients at the time of diagnosis, but also suggests that many patients acquire new abnormalities during the course of their disease. Patients with higher ZAP-70 expression may be more likely to experience such clonal evolution. These findings have important implications for both clinical management and trials of early treatment for patients with high-risk, early-stage CLL.