Maurillo Luca, Buccisano Francesco, Spagnoli Alessandra, Del Poeta Giovanni, Panetta Paola, Neri Benedetta, Del Principe Maria Ilaria, Mazzone Carla, Consalvo Maria Irno, Tamburini Anna, Ottaviani Licia, Fraboni Daniela, Sarlo Chiara, De Fabritiis Paolo, Amadori Sergio, Venditti Adriano
Dept. of Hematology, Policlinico Tor Vergata and Ospedale S.Eugenio, Rome, Italy.
Haematologica. 2007 May;92(5):605-11. doi: 10.3324/haematol.10432.
To date, bone marrow (BM) is the most common source of cells to use in order to assess minimal residual disease (MRD) in acute myeloid leukemia (AML). In the present study, we investigated whether peripheral blood (PB) could be an alternative source of cells for monitoring MRD in AML.
Fifty patients with AML were monitored for MRD after the achievement of complete remission. Using multiparametric flow cytometry we compared the levels of MRD in 50 and 48 pairs of BM and PB after induction and consolidation, respectively.
After induction and consolidation therapy, the findings in BM and PB were significantly concordant (r=0.86 and 0.82, respectively, p<0.001 for both comparisons). The cut-off value of residual leukemic cells in PB which correlated with outcome was 1.5x10 (-4). Thirty-three of 43 (77%) patients with >1.5x10 (-4)residual leukemic cells in PB after induction had a relapse, whereas the seven patients with lower levels did not (p=0.0002). After consolidation, 38 patients had a level of MRD >1.5x10 (-4)and 31 (82%) had a relapse; nine out of the remaining ten patients, whose levels of MRD were below 1.5x10 (-4), are still relapse-free (p=0.00006). In multivariate analysis, PB MRD status at the end of consolidation was found to have a significant effect on relapse-free survival (p=0.036).
These preliminary results indicate that: (i) PB evaluation can integrate BM assessment for MRD detection in patients with AML; (ii) PB MRD status at the end of consolidation therapy may provide useful prognostic information.
迄今为止,骨髓(BM)是用于评估急性髓系白血病(AML)微小残留病(MRD)最常用的细胞来源。在本研究中,我们调查了外周血(PB)是否可作为监测AML患者MRD的替代细胞来源。
50例AML患者在达到完全缓解后接受MRD监测。使用多参数流式细胞术,我们分别比较了诱导和巩固治疗后50对骨髓和外周血以及48对骨髓和外周血中的MRD水平。
诱导和巩固治疗后,骨髓和外周血中的结果显著一致(分别为r = 0.86和0.82,两种比较的p均<0.001)。与预后相关的外周血残留白血病细胞的临界值为1.5×10(-4)。诱导后外周血中残留白血病细胞>1.5×10(-4)的43例患者中有33例(77%)复发,而残留水平较低的7例患者未复发(p = 0.0002)。巩固治疗后,38例患者的MRD水平>1.5×10(-4),其中31例(82%)复发;其余10例MRD水平低于1.5×10(-4)的患者中有9例仍未复发(p = 0.00006)。多变量分析发现,巩固治疗结束时的外周血MRD状态对无复发生存有显著影响(p = 0.036)。
这些初步结果表明:(i)外周血评估可用于补充AML患者MRD检测中的骨髓评估;(ii)巩固治疗结束时的外周血MRD状态可能提供有用的预后信息。