Tierens Anne, Bjørklund Elizabeth, Siitonen Sanna, Marquart Hanne Vibeke, Wulff-Juergensen Gitte, Pelliniemi Tarja-Terttu, Forestier Erik, Hasle Henrik, Jahnukainen Kirsi, Lausen Birgitte, Jonsson Olafur G, Palle Josefine, Zeller Bem, Fogelstrand Linda, Abrahamsson Jonas
Department of Pathobiology and Laboratory Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada.
Department of Pathology, Oslo University Hospital, Oslo, Norway.
Br J Haematol. 2016 Aug;174(4):600-9. doi: 10.1111/bjh.14093. Epub 2016 Apr 13.
Early response after induction is a prognostic factor for disease outcome in childhood acute myeloid leukaemia (AML). Residual disease (RD) detection by multiparameter flow cytometry (MFC) was performed at day 15 and before consolidation therapy in 101 patients enrolled in the Nordic Society of Paediatric Haemato-Oncology AML 2004 study. A multicentre laboratory approach to RD analysis was used. Event-free survival (EFS) and overall survival (OS) was significantly different in patients with and without RD at both time points, using a 0·1% RD cut-off level. RD-negative and -positive patients after first induction showed a 5-year EFS of 65 ± 7% and 22 ± 7%, respectively (P < 0·001) and an OS of 77 ± 6% (P = 0·025) and 51 ± 8%. RD-negative and -positive patients at start of consolidation therapy had a 5-year EFS of 57 ± 7% and 11 ± 7%, respectively (P < 0·001) and an OS of 78 ± 6% and 28 ± 11%) (P < 0·001). In multivariate analysis only RD was significantly correlated with survival. RD before consolidation therapy was the strongest independent prognostic factor for EFS [hazard ratio (HR):5·0; 95% confidence interval (CI):1·9-13·3] and OS (HR:7·0; 95%CI:2·0-24·5). In conclusion, RD before consolidation therapy identifies patients at high risk of relapse in need of intensified treatment. In addition, RD detection can be performed in a multicentre setting and can be implemented in future trials.
诱导治疗后的早期反应是儿童急性髓系白血病（AML）疾病预后的一个预测因素。在北欧儿科血液肿瘤学会AML 2004研究纳入的101例患者中，于第15天和巩固治疗前通过多参数流式细胞术（MFC）检测残留病（RD）。采用多中心实验室方法进行RD分析。在两个时间点，采用0.1%的RD临界值水平时，有RD和无RD的患者的无事件生存期（EFS）和总生存期（OS）有显著差异。首次诱导后RD阴性和阳性患者的5年EFS分别为65±7%和22±7%（P<0.001），OS分别为77±6%（P=0.025）和51±8%。巩固治疗开始时RD阴性和阳性患者的5年EFS分别为57±7%和11±7%（P<0.001），OS分别为78±6%和28±11%（P<0.001）。在多变量分析中，只有RD与生存显著相关。巩固治疗前的RD是EFS[风险比（HR）：5.0；95%置信区间（CI）：1.9 - 13.3]和OS（HR：7.0；95%CI：2.0 - 24.5）的最强独立预后因素。总之，巩固治疗前的RD可识别出需要强化治疗的高复发风险患者。此外，RD检测可在多中心环境中进行，并可在未来试验中实施。
