title: 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.
abstract: 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.
authors.affiliation: Department of Woman and Child Health, Laboratory of Haematology-Oncology, University of Padova, Padova, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Buldini
authors.affiliation: Department of Woman and Child Health, Laboratory of Haematology-Oncology, University of Padova, Padova, Italy.
authors.forename: Frida
authors.initials: F
authors.lastname: Rizzati
authors.affiliation: Department of Pediatrics, Lalla Seragnoli, Haematology-Oncology Unit, University of Bologna, Bologna, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Masetti
authors.affiliation: Pediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Torino, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Fagioli
authors.affiliation: Department of Pediatric Haemato-Oncology, Santobono-Pausilipon Hospital, Napoli, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Menna
authors.affiliation: Department of Pediatric Haemato-Oncology, IRCCS Istituto "Giannina Gaslini", Genova, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Micalizzi
authors.affiliation: Department of Woman and Child Health, Laboratory of Haematology-Oncology, University of Padova, Padova, Italy.
authors.forename: Maria Caterina
authors.initials: MC
authors.lastname: Putti
authors.affiliation: Department of Pediatrics, Centro Ricerca Tettamanti, Università di Milano-Bicocca, Monza, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Rizzari
authors.affiliation: Department of Pediatrics, Policlinico di Bari, Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Santoro
authors.affiliation: Department of Pediatric Haemato-Oncology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.affiliation: Department of Woman and Child Health, Laboratory of Haematology-Oncology, University of Padova, Padova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Disarò
authors.affiliation: Department of Pediatrics, Lalla Seragnoli, Haematology-Oncology Unit, University of Bologna, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rondelli
authors.affiliation: Department of Pediatric Haematology-Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Bambino Gesù, Rome; University of Pavia, Pavia, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Merli
authors.affiliation: Department of Woman and Child Health, Laboratory of Haematology-Oncology, University of Padova, Padova, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Pigazzi
authors.affiliation: Department of Pediatrics, Lalla Seragnoli, Haematology-Oncology Unit, University of Bologna, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.affiliation: Department of Pediatric Haematology-Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Bambino Gesù, Rome; University of Pavia, Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Department of Woman and Child Health, Laboratory of Haematology-Oncology, University of Padova, Padova, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality*; D008297:Male; D015999:Multivariate Analysis; D018365:Neoplasm, Residual / Q000175:diagnosis*; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: Acute myeloid leukaemia; Flow-cytometry; Minimal residual disease; Paediatric; Risk group