急性髓细胞性白血病患者微小残留病流式细胞术检测的临床意义

The clinical significane of detecting minimal residual disease with acute myeloid leukemia by flow cytometry

目的探讨流式细胞术检测急性髓细胞性白血病(AML)微小残留病(MRD)的临床意义。方法对21例生存24～128个月成年人 AML 完全缓解(CR)患者,采用双色直接免疫荧光标记及多参数流式细胞术每隔3～12个月检测一次外周血中 MRD,同时检测骨髓细胞形态的变化。结果 21例动态检测 MRD 水平>10^(-4)患者复发率为80.0%,MRD 水平≤10^(-4)患者复发率为18.1%。21例随访24～128个月,复发10例,其中有3例先髓外复发,未复发有11例。10例 MRD 水平>10^(-4)患者24个月 EFS率为30.0%;11例 MRD 水平≤10^(-4)患者为90.9%。MRD 水平≤10^(-4)患者中复发的2例,分别在 MRD 水平升为10^(-2)后3个月、7个月时出现骨髓复发。结论 MRD 水平为10^(-3)或以上的患者预后较差,易复发。MRD 水平长时间波动在10^(-3)～10^(-4)间,即使骨髓无复发,也要警惕髓外复发。MRD 水平≤10^(-4)者生存期长,预后较好。但在生存期超过5年停化疗后,仍应动态监测 MRD 水平,尤其当 MRD 水平升至10^(-2)水平时应警防复发,甚至考虑采用干预治疗。

Objective Flow cytometry may be used to detect minimal residual disease(MRD)in acute myeloid leukemia(AML).The present study was designed to establish a flow cytometic method for detecting MRD in AML and evaluate its clinical prognostic value.Methods Fifteen cases with AML in complete re- mission(CR)survived 24～128 months.The assary of MDR were made by using the double direct immunofluo- rescence labeling and multy-paramater flow cytometry technology.The specimens for test were peripheral blood once every 3～12 months and examined bone marrow cell morphology.Results In 21 cases at CR, MRD levels>10^(-4) have 80.0% of recurrence rate and MRD levels≤10^(-4) have 18.1%.The patients with MRD levels>10^(-4) at 24 months of therapy had significantly low event free survival compared with patients of MRD levels≤10^(-4).Two out of eleven patients with MRD levels≤10^(-4) had recurrence in the bone marrow (BM)during 3 and 7 months with MRD levels≥10^(-2).Conclusion Patients with MRD levels≥10^(-2) had poor prognosis.The replase of extra-BM often occur at MRD levels of 10^(-3)～10^(-4).Though patients with MRD levels≤10^(-4) had long survival,we must detect dynamly MRD level.It is able to provide strong evidence for predict relapse and select individualized treatment in clinic.