文章：

急性髓性白血病患者诱导方案与p-糖蛋白表达的相互作用分析：来自MRC AML15试验的结果

Analysis of the interaction of induction regimens with p-glycoprotein expression in patients with acute myeloid leukaemia: results from the MRC AML15 trial

原文发布日期：2011-06-17

DOI: 10.1038/bcj.2011.23

类型: Original Article

开放获取: 是

英文摘要：

Retrospective analyses in non-randomised cohorts suggest that regimens containing fludarabine/Ara C and/or idarubicin/ara C may be more effective than daunorubicin/AraC (DA)-containing regimens in cases of acute myeloid leukaemia (AML) overexpressing p-glycoprotein (Pgp). We prospectively measured Pgp protein and function by flow cytometry in CD45-gated blasts from 434 AML15 trial patients randomised to remission induction therapy with two courses of FLAG-Ida or DA±etoposide (DA/ADE). In all, 34% were positive for Pgp protein and 38% for function. Pgp protein-positive cases had a higher incidence of resistant disease (14% vs 5%), adjusted odds ratio 2.67 (1.14–6.24). There was a trend towards a higher cumulative incidence of relapse at 5 years for Pgp-positive cases (46% vs 55%), adjusted hazard ratio 1.42 (0.98–2.07) (P=0.06). For patients treated with FLAG-Ida, the complete remission (CR) rate was 86% for both Pgp-positive and Pgp-negative patients. In patients treated with DA/ADE, 78% of Pgp-positive and 90% of Pgp-negative cases achieved CR (P=0.06). In analyses of overall survival, there was no interaction between treatment received and Pgp expression. Data for Pgp function followed similar trends. Our data suggest that FLAG-Ida may improve the remission rate for Pgp-positive AML, but the malignant clone is reduced rather than eradicated such that the relapse rate remains high in Pgp-positive patients.

摘要翻译： 

对非随机队列的回顾性分析表明，在过度表达P-糖蛋白（Pgp）的急性髓系白血病（AML）病例中，包含氟达拉滨/阿糖胞苷和/或伊达比星/阿糖胞苷的方案可能比含柔红霉素/阿糖胞苷（DA）的方案更有效。我们通过流式细胞术前瞻性检测了434名AML15试验患者中CD45设门后的原始细胞的Pgp蛋白及其功能，这些患者被随机分配接受两个疗程的FLAG-Ida或DA±依托泊苷（DA/ADE）进行缓解诱导治疗。总体而言，34%的患者Pgp蛋白阳性，38%的患者Pgp功能阳性。Pgp蛋白阳性病例的耐药性疾病发生率更高（14%对5%），调整后的优势比为2.67（1.14-6.24）。Pgp阳性病例的5年累积复发率有更高趋势（46%对55%），调整后的风险比为1.42（0.98-2.07）（P=0.06）。在接受FLAG-Ida治疗的患者中，Pgp阳性和Pgp阴性患者的完全缓解（CR）率均为86%。在接受DA/ADE治疗的患者中，78%的Pgp阳性病例和90%的Pgp阴性病例达到CR（P=0.06）。在总生存期分析中，接受的治疗与Pgp表达之间没有交互作用。Pgp功能的数据也呈现相似趋势。我们的数据表明，FLAG-Ida可能提高Pgp阳性AML的缓解率，但恶性克隆只是被减少而非根除，因此Pgp阳性患者的复发率仍然很高。

原文链接：

Analysis of the interaction of induction regimens with p-glycoprotein expression in patients with acute myeloid leukaemia: results from the MRC AML15 trial