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药物诱导凋亡试验对B细胞慢性淋巴细胞白血病患者化疗反应的预测价值

Drug induction apoptosis assay as predictive value of chemotherapy response in patients with B-cell chronic lymphocytic leukemia.

作者信息

Castejón Raquel, Yebra Miguel, Citores María-Jesús, Villarreal Mercedes, García-Marco José A, Vargas Juan A

机构信息

Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro, Universidad Autonoma de Madrid, Madrid, Spain.

出版信息

Leuk Lymphoma. 2009 Apr;50(4):593-603. doi: 10.1080/10428190902780669.

Abstract

A large number of prognostic factors are available to help predict the course of the disease for patients with B-cell chronic lymphocytic leukemia (B-CLL). However, it is not clear the involvement of these well established prognostic factors in the clinical response of the patients with B-CLL to the chemotherapy. The possible association of the patient clinical-biological characteristics and the in vitro response to chemotherapic agents may serve to provide powerful predictive information to identify optimum treatment for patients. An apoptosis induction assay displays the patient in vitro responses to chemotherapy and the possible association with their clinical-biological characteristics. In this study, patients showed a significant better in vitro response to drugs when they were in the initial stages of the disease or with low beta(2) microglobulin serum level. Response to purine analogues was significantly higher in patients with long lymphocyte doubling time (LDT), few cells expressing CD38, normal karyotype or no p53 deletion, whereas there was no correspondence with ZAP-70 expression. Furthermore, a good correlation was shown between in vitro apoptosis induction assay and the patient clinical response to purine analogues. In conclusion, association between in vitro drug sensitivity and some of the markers considered as prognostic factors could help to develop personalised therapeutic regimens for patients with B-CLL.

摘要

有大量的预后因素可用于帮助预测B细胞慢性淋巴细胞白血病(B-CLL)患者的疾病进程。然而,尚不清楚这些已确立的预后因素在B-CLL患者对化疗的临床反应中的作用。患者的临床生物学特征与对化疗药物的体外反应之间的可能关联,可能有助于为确定患者的最佳治疗方案提供有力的预测信息。凋亡诱导试验可显示患者对化疗的体外反应以及与他们临床生物学特征的可能关联。在本研究中,患者在疾病初期或β2微球蛋白血清水平较低时,对药物的体外反应明显更好。淋巴细胞倍增时间(LDT)长、表达CD38的细胞少、核型正常或无p53缺失的患者对嘌呤类似物的反应明显更高,而与ZAP-70表达无相关性。此外,体外凋亡诱导试验与患者对嘌呤类似物的临床反应之间显示出良好的相关性。总之,体外药物敏感性与一些被视为预后因素的标志物之间的关联,可能有助于为B-CLL患者制定个性化的治疗方案。

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