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Br J Haematol. 2017 Apr;177(1):116-126. doi: 10.1111/bjh.14523. Epub 2017 Feb 27.

Prognostic significance of flow-cytometry evaluation of minimal residual disease in children with acute myeloid leukaemia treated according to the AIEOP-AML 2002/01 study protocol.

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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.
Pediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Torino, Italy.
Department of Pediatric Haemato-Oncology, Santobono-Pausilipon Hospital, Napoli, Italy.
Department of Pediatric Haemato-Oncology, IRCCS Istituto "Giannina Gaslini", Genova, Italy.
Department of Pediatrics, Centro Ricerca Tettamanti, Università di Milano-Bicocca, Monza, Italy.
Department of Pediatrics, Policlinico di Bari, Bari, Italy.
Department of Pediatric Haemato-Oncology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
Department of Pediatric Haematology-Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Bambino Gesù, Rome; University of Pavia, Pavia, Italy.


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.


Acute myeloid leukaemia; Flow-cytometry; Minimal residual disease; Paediatric; Risk group

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