Qin Tiejun, Xu Zefeng, Zhang Yue, Lin Yani, Ru Kun, Fang Liwei, Zhang Hongli, Pan Lijuan, Hu Naibo, Qu Shiqiang, Wang Jingya, Xing Ruixian, Xiao Zhijian
Institute of Hematology and Blood Disease Hospital, CAMS & PUMC, State Key Laboratory of Experimental Hematology, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2016 Feb;37(2):94-9. doi: 10.3760/cma.j.issn.0253-2727.2016.02.002.
To estimate the long-term outcomes and the prognostic factors of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia (AML).
The CR rate, overall survival (OS) rate, relapse free survival (RFS) rate were retrospectively assayed in 143 de novo AML patients who received the HAD/HAI induction chemotherapy. The outcomes were compared among prognostic groups according to world health organization (WHO) classification, genetic prognosis and initial white blood cell (WBC) count. The role of consolidation chemotherapy consisting of middle-dosage Ara-C (MD-Ara-C) on long term survival was evaluated.
Of 143 patients, 112 (78.3%) achieved CR after the first course of HAD/HAI induction treatment, and early death occurred in only one case. Notably, the CR rate of patients with an initial WBC count ≥100×10(9)/L was not significantly different from those with an initial WBC count<100× 10(9)/L (70.4% vs 80.2%, P=0.266). The CR rate for the patients with favorable, intermediate and unfavorable integrated genetics risk factors was 93.7%, 71.4% and 61.3%, respectively, the difference between groups was statistically significant (P=0.001). Patients with FLT3-ITD mutation obtained similar CR rate (70.6%) to that of patients with FLT3 wild type (79.3%, P=0.528).The estimated 5-year OS rate and 5-year RFS rate for all patients was 40.0% and 37.0%, respectively, with a median follow-up of 24 (range 1-104) months. The median survival time was 30 [95%CI (12, 48)] months. 5-year OS and 5-year RFS of the 96 patients who achieved CR after first course chemotherapy without undergoing allo-HSCT in complete remission was 47.0% and 38.0%, respectively. 5-year OS was significantly higher in MD-Ara-C consolidation group than in no MD-Ara-C consolidation group among CR patients without allo-HSCT (58.0%, 19.0%, respectively, P=0.004). In patients who obtained CR after first course and received MD-Ara-C consolidation without allo-HSCT, the 5-year OS of patients with hyperleukocytosis was not significantly lower than that of patients without hyperleukocytosis (55.5%, 58.8%, respectively,P=0.419). FLT3-ITD mutation patients showed similar 5-year OS to that of wild type FLT3 patients (51.4%, 60.2%, respectively, P=0.482). And furthermore, 5-year OS of favorable, intermediate and unfavorable integrated genetics groups were 59.1%, 62.5%, 51.9%, respectively (P=0.332) in this subgroup.
HAD/HAI induction chemotherapy with sequential consolidation of MD-Ara-C could obtain satisfactory CR rate and long-term survival rate in de novo AML, especially for patients with hyperleukocytosis or FLT3-ITD mutation. It yet remains to be verified by large sample, prospective studies.
评估高三尖杉酯碱、阿糖胞苷、柔红霉素或伊达比星(HAD/HAI)作为初治急性髓系白血病(AML)诱导化疗的长期疗效及预后因素。
回顾性分析143例接受HAD/HAI诱导化疗的初治AML患者的完全缓解(CR)率、总生存(OS)率、无复发生存(RFS)率。根据世界卫生组织(WHO)分类、基因预后及初始白细胞(WBC)计数对预后分组的疗效进行比较。评估由中剂量阿糖胞苷(MD-Ara-C)组成的巩固化疗对长期生存的作用。
143例患者中,112例(78.3%)在首个疗程HAD/HAI诱导治疗后达到CR,仅1例早期死亡。值得注意的是,初始WBC计数≥100×10⁹/L的患者CR率与初始WBC计数<100×10⁹/L的患者相比无显著差异(70.4%对80.2%,P = 0.266)。具有良好、中等和不良综合遗传学危险因素的患者CR率分别为93.7%、71.4%和61.3%,组间差异有统计学意义(P = 0.001)。FLT3-ITD突变患者的CR率(70.6%)与FLT3野生型患者相似(79.3%,P = 0.528)。所有患者的估计5年OS率和5年RFS率分别为40.0%和37.0%,中位随访时间为24(范围1 - 104)个月。中位生存时间为30 [95%CI(12,48)]个月。96例在首次化疗后达到CR且未接受异基因造血干细胞移植(allo-HSCT)处于完全缓解状态的患者,其5年OS率和5年RFS率分别为47.0%和38.0%。在未接受allo-HSCT的CR患者中,MD-Ara-C巩固组的5年OS率显著高于无MD-Ara-C巩固组(分别为58.0%、19.0%,P = 0.004)。在首个疗程后达到CR且接受MD-Ara-C巩固未进行allo-HSCT的患者中,高白细胞血症患者的5年OS率不显著低于无高白细胞血症患者(分别为55.5%、58.8%,P = 0.419)。FLT3-ITD突变患者的5年OS率与FLT3野生型患者相似(分别为51.4%、60.2%,P = 0.482)。此外,在该亚组中,良好、中等和不良综合遗传学组的5年OS率分别为59.1%、62.5%、51.9%(P = 0.332)。
HAD/HAI诱导化疗序贯MD-Ara-C巩固治疗初治AML可获得满意的CR率和长期生存率,尤其对于高白细胞血症或FLT3-ITD突变患者。仍有待大样本前瞻性研究验证。