Chronic lymphocytic leukemia: A prognostic model comprising only two biomarkers (IGHV mutational status and FISH cytogenetics) separates patients with different outcome and simplifies the CLL-IPI
Chronic lymphocytic leukemia: A prognostic model comprising only two biomarkers (IGHV mutational status and FISH cytogenetics) separates patients with different outcome and simplifies the CLL-IPI
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DOI：
10.1002/ajh.24660
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发表时间：
2017-04-01
影响因子：
12.8
通讯作者：
Montserrat, Emili
中科院分区：
文献类型：
--
作者：
Delgado, Julio;Doubek, Michael;Montserrat, Emili
Rai和Binet分期系统对于预测慢性淋巴细胞白血病（CLL）患者的结局很重要，但不能反映疾病的生物多样性，也不能预测对治疗的反应，这最终影响了患者的结局。我们基于CLL中两个最重要的预后参数（即，IGHV突变状态和荧光原位杂交[FISH]细胞遗传学），将三个不同的风险组分开：（1）低风险（突变的IGHV+无不良FISH细胞遗传学[del（17 p），del（11 q）]）;（2）中等风险（未突变的IGHV或不良FISH细胞遗传学）和（3）高风险（未突变的IGHV+不良FISH细胞遗传学）。在524例未选择的CLL受试者中，低、中和高风险组的10年总生存率分别为82%（95%CI 76%-88%）、52%（45%-62%）和27%（17%-42%）。低风险患者约占该系列的50%，预期寿命与一般人群相当。在两个独立的队列中充分验证了预后模型，包括417例代表一般CLL人群的患者和337例Binet A期CLL患者。该模型具有与CLL-IPI相似的判别值。此外，它适用于所有与年龄无关的CLL患者，并将Rai或Binet临床分期中具有不同风险的患者分开。这里提出的仅生物标记物的CLL预后系统简化了CLL-IPI，并且在日常实践中可能有用，并在临床试验中对患者进行分层。
Rai and Binet staging systems are important to predict the outcome of patients with chronic lymphocytic leukemia (CLL) but do not reflect the biologic diversity of the disease nor predict response to therapy, which ultimately shape patients' outcome. We devised a biomarkers-only CLL prognostic system based on the two most important prognostic parameters in CLL (i.e., IGHV mutational status and fluorescence in situ hybridization [FISH] cytogenetics), separating three different risk groups: (1) low-risk (mutated IGHV+no adverse FISH cytogenetics [del(17p), del(11q)]); (2) intermediate-risk (either unmutated IGHV or adverse FISH cytogenetics) and (3) high-risk (unmutated IGHV+adverse FISH cytogenetics). In 524 unselected subjects with CLL, the 10-year overall survival was 82% (95% CI 76%-88%), 52% (45%-62%), and 27% (17%-42%) for the low-, intermediate-, and high-risk groups, respectively. Patients with low-risk comprised around 50% of the series and had a life expectancy comparable to the general population. The prognostic model was fully validated in two independent cohorts, including 417 patients representative of general CLL population and 337 patients with Binet stage A CLL. The model had a similar discriminatory value as the CLL-IPI. Moreover, it applied to all patients with CLL independently of age, and separated patients with different risk within Rai or Binet clinical stages. The biomarkers-only CLL prognostic system presented here simplifies the CLL-IPI and could be useful in daily practice and to stratify patients in clinical trials.