Objective: To explore impact of minimal residual leukemia (MRD) on outcomes in the non-favorable risk adults with de novo acute myeloid leukemia (AML) . Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed non-favorable risk adults with AML (non-APL) according to SWOG criteria who achieved morphologic leukemia-free state (MLFS) and received continuous chemotherapy were assessed retrospectively. Results: 292 AML patients were enrolled, 150 (51.4%) were male. Median age was 46 years (range, 18-65 years) . Using the SWOG cytogenetic classification, 186 (63.7%) , 49 (16.8%) and 57 (19.5%) patients belonged to intermediate, unfavorable and unknown categories, respectively. With a median follow-up period of 15 months (range, 1 to 94 months) in survivors, the probabilities of cumulative rates of relapse (CIR) , disease free survival (DFS) and overall survival (OS) at 2-years were 51.6%, 42.6% and 60.0%, respectively. Multivariate analyses showed that MRD positive (defined as Q-PCR WT1 mRNA ≥0.6% or any level of abnormal blast population detected by flow cytometry) after achieving MLFS and PLT<100×10(9)/L were common adverse factors affecting CIR and DFS. In addition, positive FLT3-ITD mutation and CRp/CRi had negatively impact on CIR, DFS and OS. Monosomal karyotype was adverse factors affecting CIR and OS. Age ≥44 years and unfavorable-risk of SWOG criteria were associated with shorter DFS. Conclusions: MRD level after achieving MLFS had prognostic significance on outcomes in non-favorable adults with AML who received continuous chemotherapy after achieving MLFS.
目的： 探讨微小残留病（MRD）对初治成人急性髓系白血病（AML）非预后良好型持续化疗患者预后的影响。 方法： 回顾2008年1月至2016年2月收治的按美国西南肿瘤协作组（SWOG）危险度分组为非预后良好型、获得形态学无白血病状态（MLFS）后持续化疗的AML（非急性早幼粒细胞白血病）连续病例，分析诊断时特征、诱导化疗方案、首次获得MLFS时MRD水平（MRD阳性定义为实时荧光定量PCR检测WT1 mRNA≥0.6%或流式细胞术发现残留白血病细胞）与预后的关系。 结果： 292例患者中，男150例（51.4%)，中位年龄46（18~65）岁。SWOG分组：中危186例（63.7%），高危49例（16.8%），未知57例（19.5%）。单体核型15例（5.1%），FLT3-ITD突变阳性45例（15.4%），完全缓解（CR，MLFS伴ANC≥1×10(9)/L和PLT≥100×10(9)/L）231例（79.1%），CRp（MLFS伴PLT未恢复）25例（8.6%），CRi（MLFS伴ANC和PLT均未恢复）36例（12.3%）。189例（64.7%）存活者中位随访15（1~94）个月，2年累积复发率（CIR）、无病生存（DFS）和总生存（OS）率分别为51.6%、42.6%和60.0%。多因素分析显示：MLFS时MRD阳性、PLT<100×10(9)/L是影响患者CIR和DFS的共同不利因素。FLT3-ITD突变阳性和MLFS时血细胞恢复不良是影响患者CIR、DFS和OS的共同不利因素。单体核型是影响患者CIR和OS的不利因素。此外，年龄≥44岁和SWOG危险度分组为高危组是影响DFS的不利因素。 结论： 对于非预后良好型获得MLFS后持续化疗的成人AML患者，MLFS时MRD水平是独立于年龄、诊断时血液学或分子遗传学特征之外影响预后的重要因素。.
Keywords: Leukemia, myeloid, acute; Minimal residual disease; Prognosis.