Feller N, van der Pol M A, van Stijn A, Weijers G W D, Westra A H, Evertse B W, Ossenkoppele G J, Schuurhuis G J
Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
Leukemia. 2004 Aug;18(8):1380-90. doi: 10.1038/sj.leu.2403405.
Outgrowth of minimal residual disease (MRD) in acute myeloid leukaemia (AML) is responsible for the occurrence of relapses. MRD can be quantified by immunophenotyping on a flow cytometer using the expression of leukaemia-associated phenotypes. MRD was monitored in follow-up samples taken from bone marrow (BM) of 72 patients after three different cycles of chemotherapy and from autologous peripheral blood stem cell (PBSC) products. The MRD% in BM after the first cycle (n=51), second cycle (n=52) and third cycle (n=30), as well as in PBSC products (n=39) strongly correlated with relapse-free survival. At a cutoff level of 1% after the first cycle and median cutoff levels of 0.14% after the second, 0.11% after the third cycle and 0.13% for PBSC products, the relative risk of relapse was a factor 6.1, 3.4, 7.2 and 5.7, respectively, higher for patients in the high MRD group. Also, absolute MRD cell number/ml was highly predictive of the clinical outcome. After the treatment has ended, an increase of MRD% predicted forthcoming relapses, with MRD assessment intervals of < or =3 months. In conclusion, MRD parameter assessment at different stages of disease is highly reliable in predicting survival and forthcoming relapses in AML.
急性髓系白血病（AML）中微小残留病（MRD）的进展是复发发生的原因。MRD可通过流式细胞仪上白血病相关表型的表达进行免疫表型分析来定量。在72例患者接受三个不同化疗周期后采集的骨髓（BM）随访样本以及自体外周血干细胞（PBSC）产物中监测MRD。第一个周期（n = 51）、第二个周期（n = 52）和第三个周期（n = 30）后BM中的MRD%以及PBSC产物（n = 39）中的MRD%与无复发生存期密切相关。在第一个周期后截断水平为1%，第二个周期后中位数截断水平为0.14%，第三个周期后为0.11%，PBSC产物为0.13%时，高MRD组患者的复发相对风险分别高出6.1、3.4、7.2和5.7倍。此外，每毫升绝对MRD细胞数对临床结局具有高度预测性。治疗结束后，MRD%的增加预示即将复发，MRD评估间隔≤3个月。总之，在疾病不同阶段进行MRD参数评估在预测AML的生存和即将复发方面高度可靠。
