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. 2018 Jan 14;39(1):15-21.
doi: 10.3760/cma.j.issn.0253-2727.2018.01.004.

[Outcomes of adult patients with de novo acute myeloid leukemia received idarubicin plus cytarabine regimen as induction chemotherapy]

[Article in Chinese]
Affiliations

[Outcomes of adult patients with de novo acute myeloid leukemia received idarubicin plus cytarabine regimen as induction chemotherapy]

[Article in Chinese]
X Ren et al. Zhonghua Xue Ye Xue Za Zhi. .

Abstract

Objective: To explore outcomes in adult with de novo acute myeloid leukemia (AML) received IA10 (10 mg/m(2) d1-3 idarubicin plus cytarabine 100 mg/m(2) d1-7) regimen as induction chemotherapy. Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-M(3)) adults treated with IA10 who achieved morphologic leukemia-free state (MLFS) but not accepted allogeneic hematopoietic stem cell transplantation (allo-HSCT) were assessed retrospectively. Results: A total of 198 patients were included in this study with 96 (48.5%) male and a median age of 42 years old (range, 18-62 years old). Using the SWOG cytogenetic classification, 45 (22.7%), 104 (52.5%), 24 (12.1%) and 25 (12.6%) patients belonged to favorable, intermediate, unfavorable and unknown categories, respectively. 6 (3.0%) patients had monosomal karyotype, and 28 (14.1%) positive FLT3-ITD mutation. A complete remission (CR, defined as MLFS with ANC ≥ 1×10(9)/L and PLT ≥ 100×10(9)/L) achieved in 168 (84.8%) patients, a CRp (defined as MLFS with incomplete PLT recovery) in 16 (8.1%) and a CRi (defined as MLFS with incomplete ANC and PLT recovery) in 14 (7.1%). With a median follow-up period of 15 months (range, 1 to 70 months) in survivors, the probabilities of cumulative incident of relapse (CIR), disease free survival (DFS) and overall survival (OS) rates at 2-year were 45.2%, 46.9% and 62.9%, respectively; the median durations of relapse, DFS and OS were 34, 20 and 37 months respectively. At the time of achieving first MLFS, multivariate analyses showed that positive FLT3-ITD mutation and CRi were common adverse factors affecting CIR, DFS and OS; unfavorable-risk of SWOG criteria was an adverse factor affecting CIR and DFS; monosomal karyotype was associated with shorter OS. After first consolidation therapy, FLT3-ITD mutation positive and unfavorable-risk of SWOG criteria had negatively impact on CIR, DFS and OS; peripheral blasts ≥ 0.50 and positive MRD (defined as RQ-PCR WT1 mRNA ≥ 0.6% or any level of abnormal blast population detected by flow cytometry) after first consolidation therapy were common adverse factors affecting CIR and DFS; CRi was an adverse factor affecting DFS and OS. Conclusions: In adult with de novo AML received IA10 regimen as induction regimen, unfavorable molecular markers or cytogenetics at diagnosis and CRi independently predicted poor outcome. In addition, a higher percentage of peripheral blasts, monosomal karyotype and positive MRD after first consolidation therapy had negatively impact on outcomes.

目的: 探讨接受IA10[去甲氧柔红霉素(IDA)10 mg·m(-2)·d(-1)×3 d联合阿糖胞苷(Ara-C)100 mg·m(-2)·d(-1)×7 d]作为诱导方案且未接受异基因造血干细胞移植(allo-HSCT)的成人急性髓系白血病(AML)患者的预后影响因素。 方法: 回顾2008年1月至2016年2月收治的接受IA10作为诱导化疗方案、获得形态学无白血病状态(MLFS)后未接受allo-HSCT的198例AML(不包括急性早幼粒细胞白血病)连续病例,分析诊断时特征、首次获得MLFS时血细胞恢复程度、首次获得MLFS时和巩固1个疗程后微小残留病(MRD)水平对预后的影响。 结果: 198例患者中,男96例(48.5%),中位年龄42(18~62)岁。SWOG分组:低危45例(22.7%),中危104例(52.5%),高危24例(12.1%),危险度未知25例(12.6%)。FLT3-ITD突变阳性28例(14.1%)。完全缓解(CR,MLFS伴ANC≥1×10(9)/L和PLT≥100×10(9)/L)168例(84.8%),CRp(MLFS伴PLT未恢复)16例(8.1%),CRi(MLFS伴ANC和PLT均未恢复)14例(7.1%)。131例(66.2%)存活患者中位随访时间15(1~70)个月,2年累积复发率(CIR)、无病生存(DFS)、总生存(OS)率分别为45.2%、46.9%、62.9%,中位复发、DFS、OS时间分别为34、20、37个月。在所有获得MLFS的患者中进行多因素分析,FLT3-ITD突变阳性和CRi是影响患者CIR、DFS、OS的共同不利因素;SWOG危险度为高危是影响患者CIR和DFS的共同不利因素;单体核型是影响患者OS的独立危险因素。分析接受巩固治疗≥1个疗程的患者,FLT3-ITD突变阳性和SWOG危险度为高危是影响患者CIR、DFS、OS的共同不利因素;外周血原始细胞≥0.50和巩固治疗1个疗程后MRD阳性[FCM和(或)WT1 mRNA阳性]是影响患者CIR和DFS的共同不利因素;CRi是影响患者DFS和OS的共同不利因素。 结论: 对于接受IA10作为诱导方案且获得MLFS后未接受allo-HSCT的初治成人AML患者,初诊时不良的遗传学特征和CRi是影响患者总体预后的不利因素。此外,外周血原始细胞比例高、单体核型和巩固治疗1个疗程后MRD阳性也与预后不良相关。.

Keywords: Idarubicin; Leukemia, myeloid, acute; Prognosis.

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Figures

图1
图1. 具有不同危险因素患者的累积复发(A)、无病生存(B)和总生存(C)曲线
注:危险因素包括外周原始细胞≥0.50、FLT3-ITD 突变阳性、SWOG危险度分层高危、CRi和巩固1个疗程后微小残留病阳性

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