Ustün C, Beksac M, Dalva K, Koc H, Konuk N, Ilhan O, Ozcan M, Topcuoglu P, Sertkaya D, Hayran M
Department of Hematology, Ankara University, School of Medicine, Sihhiye, Turkey.
Med Oncol. 2002;19(1):59-67. doi: 10.1385/MO:19:1:59.
All-trans retinoic acid (ATRA) is used in the treatment of acute promyelocytic leukemia. Because ATRA has effects (increase in apoptosis, suppression of bcl-2), it has also been used for the treatment of other French-American-British (FAB) subtypes of acute myelogenous leukemia (AML). To find out the in vivo and in vitro effects of ATRA in AML, we analyzed 37 patients with de novo AML. Twenty-seven patients received ATRA before remission-induction (RI) treatment (ATRA group). Results were compared to a control group (10 patients) that received induction without ATRA during the same time period. Bone marrow or peripheral blood samples were collected from all patients on d 0 and 4. The immunphenotype, myeloperoxidase (MPO), reac tion and the efflux uptake of rhodamine 123 (Rh123) were analyzed on myeloblasts in these samples. In the myeloblasts from patients treated with ATRA, the uptake of Rh123 was increased significantly (p = 0.026) from d 0 to d 4, and all other parameters remained unaltered. ATRA administration increased the complete remission (CR) rate (88%, 22/25 vs 55%, 5/9) significantly (p = 0.042). Logistic regression analysis revealed that ATRA administration was the important factor in CR, among other potential factors including age, white blood count, bcl-2 expression, and the uptake and efflux of Rh123 (p = 0.05). Estimated disease-free survival and overall survival were similar between these two groups (43% vs 37.5% and 51.2% vs 37.5%, respectively). In conclusion, ATRA treatment prior to RI treatment may improve the CR rate in patients with de novo AML, which seems to be related to its beneficial effect on multidrug resistance.
全反式维甲酸（ATRA）用于治疗急性早幼粒细胞白血病。由于ATRA具有一些作用（增加细胞凋亡、抑制bcl-2），它也被用于治疗急性髓系白血病（AML）的其他法美英（FAB）亚型。为了探究ATRA在AML中的体内和体外作用，我们分析了37例初发AML患者。27例患者在缓解诱导（RI）治疗前接受了ATRA治疗（ATRA组）。将结果与同期接受无ATRA诱导治疗的对照组（10例患者）进行比较。在第0天和第4天从所有患者采集骨髓或外周血样本。对这些样本中的原始粒细胞进行免疫表型、髓过氧化物酶（MPO）、反应以及罗丹明123（Rh123）的流出摄取分析。在接受ATRA治疗的患者的原始粒细胞中，从第0天到第4天，Rh123的摄取显著增加（p = 0.026），而所有其他参数保持不变。给予ATRA显著提高了完全缓解（CR）率（88%，22/25 vs 55%，5/9）（p = 0.042）。逻辑回归分析显示，在包括年龄、白细胞计数、bcl-2表达以及Rh123的摄取和流出等其他潜在因素中，给予ATRA是CR的重要因素（p = 0.05）。两组之间的估计无病生存期和总生存期相似（分别为43% vs 37.5%和51.2% vs 37.5%）。总之，RI治疗前进行ATRA治疗可能提高初发AML患者的CR率，这似乎与其对多药耐药的有益作用有关。
