Shanafelt Tait D, Witzig Thomas E, Fink Stephanie R, Jenkins Robert B, Paternoster Sarah F, Smoley Stephanie A, Stockero Kimberly J, Nast Danielle M, Flynn Heather C, Tschumper Renee C, Geyer Susan, Zent Clive S, Call Tim G, Jelinek Diane F, Kay Neil E, Dewald Gordon W
Mayo Clinic College of Medicine, Department of Internal Medicine, Division of Hematology, Rochester, MN 55905, USA.
J Clin Oncol. 2006 Oct 1;24(28):4634-41. doi: 10.1200/JCO.2006.06.9492.
Retrospective 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.
Between 1994 and 2002, we enrolled 159 patients with previously untreated CLL (83% Rai stage 0/I) on a prospective trial evaluating clonal evolution by FISH. Patients provided baseline and follow-up specimens for FISH testing during 2 to 12 years.
Chromosomal 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).
This 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.
回顾性研究表明，通过间期荧光原位杂交（FISH）检测到的细胞遗传学异常可识别出慢性淋巴细胞白血病（CLL）患者中那些疾病进程更为侵袭性的患者。其他研究表明，患者在疾病过程中可能会获得染色体异常。对于新诊断的早期CLL患者中广泛使用的分级FISH预后分类的临床实用性，或间期FISH确定的克隆演变频率，前瞻性数据极少。
1994年至2002年期间，我们招募了159例未经治疗的CLL患者（83%为Rai 0/I期）参与一项前瞻性试验，该试验通过FISH评估克隆演变。患者在2至12年期间提供基线和随访标本用于FISH检测。
研究入组时通过FISH检测到的染色体异常可预测总生存期。18例患者在随访期间发生了克隆演变。克隆演变率随随访时间延长而增加，在前2年仅有1例（n = 71；1.4%），但在5年以上接受检测的患者中有17例（n = 63；27%）。5年以上时，10%的ZAP-70阴性患者和42%的ZAP-70阳性患者发生了克隆演变（P = 0.008）。
这项临床试验前瞻性地证实，FISH检测到的细胞遗传学异常可在诊断时预测CLL患者的总生存期，但也表明许多患者在疾病过程中会获得新的异常。ZAP-70表达较高的患者可能更易发生此类克隆演变。这些发现对高危早期CLL患者的临床管理和早期治疗试验均具有重要意义。
