Buldini Barbara, Rizzati Frida, Masetti Riccardo, Fagioli Franca, Menna Giuseppe, Micalizzi Concetta, Putti Maria Caterina, Rizzari Carmelo, Santoro Nicola, Zecca Marco, Disarò Silvia, Rondelli Roberto, Merli Pietro, Pigazzi Martina, Pession Andrea, Locatelli Franco, Basso Giuseppe
Department of Woman and Child Health, Laboratory of Haematology-Oncology, University of Padova, Padova, Italy.
Department of Pediatrics, Lalla Seragnoli, Haematology-Oncology Unit, University of Bologna, Bologna, Italy.
Br J Haematol. 2017 Apr;177(1):116-126. doi: 10.1111/bjh.14523. Epub 2017 Feb 27.
In children with acute myeloid leukaemia (AML), assessment of initial treatment response is an essential prognostic factor; methods more sensitive than morphology are still under evaluation. We report on the measurement of minimal residual disease (MRD), by multicolour flow-cytometry in one centralized laboratory, in 142 children with newly diagnosed AML enrolled in the Associazione Italiana di EmatoOncologia Pediatrica-AML 2002/01 trial. At the end of the first induction course, MRD was <0·1% in 69, 0·1-1% in 16 and >1% in 51 patients. The 8-year disease-free survival (DFS) of 125 children in morphological complete remission and with MRD <0·1%, 0·1-1% and ≥1% was 73·1 ± 5·6%, 37·8 ± 12·1% and 34·1 ± 8·8%, respectively (P < 0·01). MRD was also available after the second induction course in 92/142 patients. MRD was ≥0·1% at the end of the first induction course in 36 patients; 13 reached an MRD <0·1% after the second one and their DFS was 45·4 ± 16·7% vs. 22·8 ± 8·9% in patients with persisting MRD ≥0·1% (P = 0·037). Multivariate analysis demonstrated that MRD ≥0·1% after first induction course was, together with a monosomal karyotype, an independent adverse prognostic factor for DFS. Our results show that MRD detected by flow-cytometry after induction therapy predicts outcome in patients with childhood AML and can help stratifying post-remission treatment.
在急性髓系白血病（AML）患儿中，初始治疗反应评估是一项重要的预后因素；比形态学更敏感的方法仍在评估中。我们报告了在一个集中实验室中，通过多色流式细胞术对142例新诊断为AML且参加意大利儿科血液肿瘤学会-AML 2002/01试验的患儿进行微小残留病（MRD）测量的情况。在第一个诱导疗程结束时，69例患儿的MRD<0.1%，16例患儿的MRD为0.1%-1%，51例患儿的MRD>1%。125例形态学完全缓解且MRD<0.1%、0.1%-1%和≥1%的患儿的8年无病生存率（DFS）分别为73.1±5.6%、37.8±12.1%和34.1±8.8%（P<0.01）。在92/142例患者的第二个诱导疗程后也可获得MRD数据。36例患者在第一个诱导疗程结束时MRD≥0.1%；其中13例在第二个诱导疗程后MRD<0.1%，其DFS为45.4±16.7%，而MRD持续≥0.1%的患者DFS为22.8±8.9%（P=0.037）。多变量分析表明，第一个诱导疗程后MRD≥0.1%与单倍体核型一起是DFS的独立不良预后因素。我们的结果表明，诱导治疗后通过流式细胞术检测到的MRD可预测儿童AML患者的预后，并有助于对缓解后治疗进行分层。
