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老年慢性淋巴细胞白血病:临床生物学特征、预后及预后模型的建议

Chronic lymphocytic leukemia in the elderly: clinico-biological features, outcomes, and proposal of a prognostic model.

作者信息

Baumann Tycho, Delgado Julio, Santacruz Rodrigo, Martínez-Trillos Alejandra, Royo Cristina, Navarro Alba, Pinyol Magda, Rozman María, Pereira Arturo, Villamor Neus, Aymerich Marta, López Cristina, Carrió Anna, Montserrat Emili

机构信息

Institute of Hematology and Oncology, Department of Hematology, University of Barcelona, Barcelona, Spain Hematopathology Unit, Pathology Department, University of Barcelona, Barcelona, Spain.

Institute of Hematology and Oncology, Department of Hematology, University of Barcelona, Barcelona, Spain.

出版信息

Haematologica. 2014 Oct;99(10):1599-604. doi: 10.3324/haematol.2014.107326. Epub 2014 Jun 27.

Abstract

We investigated the clinico-biological features, outcomes, and prognosis of 949 patients with chronic lymphocytic leukemia according to age. No biological differences (cytogenetics by fluorescent in situ hybridization, IGHV, ZAP-70, CD38, NOTCH1, SF3B1) were found across age groups. Elderly patients (>70 years; n=367) presented more frequently with advanced disease (Binet C/Rai III-IV: 10/12% versus 5/5%; P<0.001), were treated less frequently (23.8% versus 41.9% at 3 years; P<0.001) and in most cases did not receive highly effective regimens and thus had a lower overall response rate (49% with 14% having complete responses versus 69% with 31% having complete responses; P<0.001). The elderly patients also had a shorter overall survival (6.6 versus 13.3 years; P<0.001) and higher disease-unrelated mortality (34.9% versus 6.9% at 10 years; P<0.001). However, disease-attributable mortality was not significantly different between younger and older patients. A combination of Binet stage, ZAP-70 level, β2-microglobulin concentration and comorbidity identified two risk groups (low-risk: 0-1 parameters; high-risk: 2-4 parameters) with different overall survivals (median: 6.8 versus 11.4 years, P<0.001). In patients requiring treatment, comorbidity at treatment (Cumulative Illness Rating Scale-T>4; hazard ratio 2.2, P<0.001) and response (treatment failure versus response: hazard ratio 1.60, P<0.04) were the most important prognostic factors for overall survival. In conclusion, in our series, elderly patients with chronic lymphocytic leukemia did not present with any biological features distinct from those of younger patients, but did have a poorer clinical outcome. This study highlights the importance of comprehensive medical care, achieving response to therapy, and specific management strategies for elderly patients with chronic lymphocytic leukemia.

摘要

我们根据年龄对949例慢性淋巴细胞白血病患者的临床生物学特征、治疗结果及预后进行了研究。各年龄组之间未发现生物学差异(荧光原位杂交检测细胞遗传学、免疫球蛋白重链可变区基因[IGHV]、ζ链相关蛋白70[ZAP-70]、CD38、Notch1、剪接因子3B1[Sf3B1])。老年患者(>70岁;n = 367)疾病进展更为常见(国际预后指数[Binet]C/Rai III-IV期:10/12% 对比5/5%;P<0.001),接受治疗的频率更低(3年时分别为23.8% 对比41.9%;P<0.001),且在大多数情况下未接受高效治疗方案,因此总体缓解率较低(49%,其中14% 完全缓解对比69%,其中31% 完全缓解;P<0.001)。老年患者的总生存期也较短(6.6年对比13.3年;P<0.001),与疾病无关的死亡率更高(10年时分别为34.9% 对比6.9%;P<0.001)。然而,年轻和老年患者的疾病归因死亡率无显著差异。结合Binet分期、ZAP-70水平、β2微球蛋白浓度及合并症情况可确定两个风险组(低风险:0 - 1个参数;高风险:2 - 4个参数),其总生存期不同(中位数:6.8年对比11.4年,P<0.001)。在需要治疗的患者中,治疗时的合并症(累积疾病分级量表-T>4;风险比2.2,P<0.001)及治疗反应(治疗失败对比有反应:风险比1.60,P<0.04)是总生存期最重要的预后因素。总之,在我们的研究系列中,老年慢性淋巴细胞白血病患者未表现出与年轻患者不同的生物学特征,但临床结果较差。本研究强调了综合医疗护理、实现治疗反应以及针对老年慢性淋巴细胞白血病患者采取特定管理策略的重要性。

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