初发急性髓系白血病诱导化疗后外周血MRD早期检测与临床疗效的关系

Early Detection of MRD in Peripheral Blood after induction Chemotherapy of Newly Diagnosed Patients with AML and Its Correlation with Curative Effects

本研究旨在检测初发急性髓系白血病(AML)患者诱导化疗第8天外周血残存的白血病细胞数量,探索其与诱导缓解及生存时间之间的关系。收集华西医院血液科2009年9月至2010年6月的29例初发AML患者的临床和实验室资料,其中男13例,女16例,中位年龄41(16-75)岁。根据初诊时白血病相关免疫表型特征(LAIP),采用流式细胞术检测患者诱导化疗第8天外周血微小残留病(MRD)细胞数量;应用Kaplan-Meier法计算生存曲线,对数秩检验进行单因素生存分析,观察患者外周血化疗第8天MRD水平与治疗后完全缓解率(CR)及总体生存率之间的关系。结果表明,29例AML患者经第1疗程化疗后,7例外周血MRD水平低于0.01%(阴性组),其余22例外周血MRD水平高于0.01%(0.08%-55%,阳性组);两组患者在性别、年龄、WBC、乳酸脱氢酶水平、骨髓原始细胞比例等均无统计学差异。7例MRD阴性组中6例达CR(86%),22例MRD阳性组中6例达CR(27%),CR率差异有统计学意义(P<0.05)。随访时间1-28个月(中位时间15个月),MRD阴性组患者中位生存期为19个月,MRD阳性组患者中位生存期为9个月(P<0.05),MRD阴性组1年生存率(100%)明显高于阳性组(39.4%,P<0.01)。结论:采用流式细胞术检测AML患者诱导化疗后第8天外周血MRD水平能较好的预测患者的CR率与长期生存率,MRD阴性患者有更高的CR率和更长的生存期。

The purpose of this study was to detect the minimal residual disease （MRD） in peripheral blood of newly diagnosed patients with acut myeloid leukemia （AML） on day 8 of induction chemotherapy and analyze the correlation between day 8 MRD （D8RD） and therapeutic effectiveness. 29 adult patients （13 males and 16 females, aged 16 -75 years, median 41 years） with AML diagnosed and treated in West China Hospital from September 2009 to June 2010 were analyzed and followed up in the study. The leukemia-associated aberrant immunophenotype （LAIP） of all the patients were detected by multiparameter flow cytometry （FCM） before therapy. The level of MRD in the peripheral blood at day 8 of induction chemotherapy was detected by FCM based on the LAIP. The overall survival curve was drawn by calculation using Kaplan-Meier method using, and the comparison between different groups was carried out by Log-rank test. The results indicated that after first course therapy, the levels of peripheral D8RD in 7 out of 29 AML cases were lower than 0.01% （ negative group）, and that in another 22 cases were higher than 0.01% （0.08 % -55 %, positive group）. The sex, age, WBC, LDH, percentage of bone marrow blasts at diagnosis in these groups were not statistically different. 6 cases achieved CR（86% ） in D8RD negative group, and also 6 cases achieved CR （27%） in D8RD positive group, CR rate in D8RD negative group was higher than in D8RD positive group （86% vs 27%, P 〈 0.05 ）. The median follow-up of 29 cases lasted for 15 months; the 1-year overall survival rate of D8RD negative and D8RD positive groups was 100 % and 39.4%, respectively （ P 〈 0.01 ）. It is concluded that MRD level in peripheral blood at day 8 of induction chemotherapy is an early index to predict clinical efficacy of induction therapy in AML.