流式细胞术定期监测微量残留病可预测急性白血病复发——单中心163例研究

目的 研究急性白血病(AL)在化疗获得第1次完全缓解( CR1)后用流式细胞术(FCM)定期监测微量残留病(MRD)的预后价值.方法 对2005年4月至2009年7月北京市道培医院收治的CR1期AL患者(不包括接受造血干细胞移植者),定期用FCM监测患者骨髓MRD,追踪至复发或至2010年7月.根据每例患者的白血病特点选择抗体组合,MRD≥0.01％为阳性,否则为阴性.用Kaplan-Meier法统计持续完全缓解(CCR)率,用Log-rank检验方法比较MRD阳性与阴性患者CCR率差异.结果 163例患者中急性髓系白血病(AML) 108例,急性B淋巴细胞白血病(B-ALL)55例.89例AML患者在诊断后1年内接受MRD监测,根据化疗至12个月时的MRD检测结果将患者分为MRD阳性及阴性组:30例MRD阳性者中仅3例CCR至2010年7月,24、36个月的CCR率分别为13％、13％；59例MRD阴性者中47例CCR至2010年7月,24、36个月的CCR率分别为94％、78％；两组CCR率差异有统计学意义(P＜0.01).35例B-ALL患者在诊断后5个月内接受MRD监测,根据MRD检测结果将患者分为MRD阳性及阴性组:13例MRD阳性者无一例CCR至2010年7月,24、36个月的CCR率为0；22例MRD阴性者中20例CCR至2010年7月,24、36个月的CCR率均为96％；两组CCR率差异有统计学意义(P＜0.01).超过以上监测时间MRD阳性的其他患者均复发,而MRD持续阴性者很少复发.结论 用FCM定期监测AL的MRD有良好的预后价值.

Predictable recurrence by regular monitoring minimal residual disease with flowcytometry in the patients with acult leukemia: a single-center study of 163 cases

Objective To study the predictable value of monitoring minimal residual disease (MRD)regularly by flowcytometry (FCM) in patients with acute leukemia (AL) in the first complete remission (CR1).Methods From April 2005 to July 2009,AL patients who had got CR1 after chemotherapy were regularly monitored for MRD in bone marrow by FCM to relapse or to July 2010 in Beijing Daopei Hospital (not including those received stem cell transplantation).The special antibody combinations were employed for each patient according to aberrant expression of leukemia cells.MRD + was defined as the aberrant cells more than 0.01％.The probability of continuous CR(CCR) was calculated by Kaplan-Meier formula,and the statistical difference between two CCR probabilities was evaluated by log-rank test.Results A total of 163 AL patients in CR1 were monitored to relapse or to July 2010.Among 89 AML patients referred to our hospital within 1 year after diagnosis,30 cases were in MRD + and 59 cases MRD- till 12 months following chemotherapy,3/30 patients in MRD+ and 47/59 remained in CCR to July 2010.The probability of CCR at 24,36months was 13％,13％ in MRD + group,94％,78％ in MRD- group respectively,the difference between them was statistically significant ( P ＜ 0.01 ).Among 35 ALL referred to our hospital within 5 months after diagnosis,13 cases were MRD+ and 22 cases MRD- till 5 months following chemotherapy,0/13 patients in MRD+ and 20/22 patients in MRD - remained in CCR to July 2010.The probability of CCR at 24,36 months was 0％ in MRD+ group,96％,96％ in MRD- group respectively,the difference between them was statistically significant (P ＜0.01 ).Over the time point above,all patients with MRD + or their MRD from negative to positive relapsed finally,and most patients with MRD- remained CCR to July 2010.Conclusion It had a chnical prognostic value to monitor MRD regularly by FCM in the patients with AL after CR1.