Majlis A, Smith T L, Talpaz M, O'Brien S, Rios M B, Kantarjian H M
Department of Hematology, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
J Clin Oncol. 1996 Jan;14(1):196-203. doi: 10.1200/JCO.1996.14.1.196.
To describe the incidence and significance of clonal evolution patterns.
We analyzed 264 patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who developed clonal evolution between 1967 and 1993.
The median survival time following clonal evolution was 19 months. Factors associated with worse survival (P < .01) were as follows: chromosome 17 abnormality or chromosomal translocations other than Ph, high percentage of abnormal metaphases, longer time to clonal evolution, and presence of other accelerated-phase features. A recursive partitioning technique (CART) identified different risk groups. The best group (37 patients; no chromosome 17 abnormality, abnormal metaphases < 16%, and interval to clonal evolution < or = 24 months) had an estimated median survival time of 54 months. The worst two groups included 27 patients with chromosome 17 abnormalities and > or = 36% abnormal metaphases (estimated median survival time, 6 months), and 22 patients with other accelerated features and > or = 16% abnormal metaphases (estimated median survival time, 7 months). The intermediate group had an estimated median survival time that ranged from 13 to 24 months. Prior interferon therapy evaluated within risk groups showed a significant survival advantage only in the intermediate-risk group. A multivariate analysis showed similar results, and identified the following independent poor prognostic variables: chromosome 17 abnormality, percentage of abnormal metaphases (cutoff, 24%), longer time to clonal evolution (cutoff, 24 months), other accelerated-phase features, and no prior interferon therapy. Patients with none, one, two, three, or more of the first four features had median survivals times of 51, 24, 14, and 7 months, respectively.
The prognostic significance of clonal evolution in CML is not uniform and is related to the specific abnormality, time to its development, its predominance in metaphases, and the presence of other accelerated features, and it may be modified by specific therapies.
描述克隆进化模式的发生率及意义。
我们分析了1967年至1993年间发生克隆进化的264例费城染色体（Ph）阳性慢性髓性白血病（CML）患者。
克隆进化后的中位生存时间为19个月。与较差生存相关的因素（P <.01）如下：17号染色体异常或除Ph之外的染色体易位、异常中期细胞的高比例、克隆进化时间较长以及存在其他加速期特征。一种递归划分技术（CART）确定了不同的风险组。最佳组（37例患者；无17号染色体异常、异常中期细胞<16%且克隆进化间隔<或=24个月）的估计中位生存时间为54个月。最差的两组包括27例有17号染色体异常且异常中期细胞≥36%的患者（估计中位生存时间为6个月），以及22例有其他加速特征且异常中期细胞≥16%的患者（估计中位生存时间为7个月）。中间组的估计中位生存时间为13至24个月。在风险组内评估的既往干扰素治疗仅在中危组显示出显著的生存优势。多变量分析显示了类似结果，并确定了以下独立的不良预后变量：17号染色体异常、异常中期细胞百分比（临界值，24%）、克隆进化时间较长（临界值，24个月）、其他加速期特征以及无既往干扰素治疗。具有前四个特征中无、一个、两个、三个或更多特征的患者的中位生存时间分别为51、24、14和7个月。
CML中克隆进化的预后意义并不一致，且与特定异常、其发生时间、在中期的优势以及其他加速特征的存在有关，并且可能会因特定治疗而改变。
