Wierda William G, O'Brien Susan, Wang Xuemei, Faderl Stefan, Ferrajoli Alessandra, Do Kim-Anh, Garcia-Manero Guillermo, Cortes Jorge, Thomas Deborah, Koller Charles, Burger Jan, Lerner Susan, Kantarjian Hagop, Keating Michael
Department of Leukemia and Biostatistics and Applied Mathematics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
J Clin Oncol. 2009 Apr 1;27(10):1637-43. doi: 10.1200/JCO.2008.18.1701. Epub 2009 Feb 17.
Response to front-line treatment and subsequent clinical course for patients with chronic lymphocytic leukemia (CLL) are heterogeneous. Identifying pretreatment patient characteristics or prognostic factors associated with clinical outcomes is important for counseling patients, conducting clinical research, and evaluating trial results.
We evaluated the pretreatment characteristics of 595 previously untreated patients who had National Cancer Institute Working Group indications to initiate front-line therapy for predictors of complete response (CR), time to treatment failure (TTF), and overall survival (OS). Multivariable models were developed for all three end points.
CR is an important treatment end point correlated with longer TTF and OS. In this retrospective analysis, front-line treatment regimen was a significant independent predictive factor for all three end points; chemoimmunotherapy was the superior treatment regimen. Considering front-line treatment regimen, other independent patient characteristics associated with CR included age and beta(2)-microglobulin (beta-2M). TTF was independently associated with age, beta-2M, percent lymphocytes in bone marrow, and treatment regimen. Improved OS was independently associated with younger age, lower beta-2M, and treatment regimen. Two weighted prognostic models or nomograms, one including and one excluding treatment regimen, were constructed using significant characteristics to predict 5- and 10-year survival probability and estimate median survival time.
Identifying pretreatment patient characteristics associated with CR, TTF, and OS establishes a baseline to compare and incorporate new prognostic factors. Treatment had an impact on the significance of these factors. Prognostic models may help patients and clinicians in decision making as well as facilitate clinical research through design and analyses of clinical trials.
慢性淋巴细胞白血病（CLL）患者对一线治疗的反应及后续临床病程具有异质性。识别与临床结局相关的预处理患者特征或预后因素对于为患者提供咨询、开展临床研究以及评估试验结果至关重要。
我们评估了595例先前未接受过治疗、符合美国国立癌症研究所工作组启动一线治疗指征的患者的预处理特征，以确定完全缓解（CR）、治疗失败时间（TTF）和总生存期（OS）的预测因素。针对所有三个终点建立了多变量模型。
CR是一个重要的治疗终点，与更长的TTF和OS相关。在这项回顾性分析中，一线治疗方案是所有三个终点的显著独立预测因素；化疗免疫疗法是更优的治疗方案。考虑一线治疗方案，与CR相关的其他独立患者特征包括年龄和β2微球蛋白（β-2M）。TTF与年龄、β-2M、骨髓中淋巴细胞百分比和治疗方案独立相关。OS的改善与年龄较轻、β-2M较低和治疗方案独立相关。使用显著特征构建了两个加权预后模型或列线图，一个包括治疗方案，一个排除治疗方案，以预测5年和10年生存概率并估计中位生存时间。
识别与CR、TTF和OS相关的预处理患者特征可建立一个基线，用于比较和纳入新的预后因素。治疗对这些因素的重要性有影响。预后模型可能有助于患者和临床医生进行决策，并通过临床试验的设计和分析促进临床研究。
