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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., (© 2017 John Wiley & Sons Ltd.)

Paediatric patients with acute myeloid leukaemia (AML) who fail induction due to primary resistance to chemotherapy account for a significant proportion of cases and have a particularly dismal prognosis. We report the clinical and biological data, and final outcome of 48 paediatric patients with primary-resistant AML enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 clinical trial. These patients had a significantly higher white blood cell count at diagnosis compared to other AML patients. Cytogenetic and molecular features did not differ between patients with primary induction failure and patients allocated to the high-risk group. For the whole patient population, the probability of overall survival, event-free survival (EFS) and disease-free survival (DFS) was 21·8% ± 6·2, 20·4% ± 5·9, and 49·5% ± 11·3, respectively. Twenty-eight (58%) patients received haematopoietic stem cell transplantation (HSCT); 3 were autologous and 25 were allogeneic. Patients who underwent HSCT had improved EFS (31·2% vs. 5%, P < 0·0001). Only one of the 20 patients who did not receive HSCT is alive and disease free. The 19 patients in complete remission at time of HSCT showed significantly better DFS than the 9 with active disease (46% vs. 0%, P = 0·02). This study represents one of the largest series with long-term follow up of paediatric AML patients with primary refractory disease. Children who underwent transplantation had an encouraging long-term outcome. Disease recurrence remains the major cause of treatment failure; a better understanding of the disease biology is desirable to develop more effective treatment strategies., (© 2015 John Wiley & Sons Ltd.)

Imatinib mesylate (IM) is used for the management of childhood chronic myeloid leukaemia (CML). The most effective dosage of IM and its long-term efficacy in children are not well defined. The purpose of this multicentre study is to report on the long-term results of high-dose IM (340 mg/m2 /d) in CML patients in chronic phase (CP-CML) aged <18 years at diagnosis. A total of 47 CP-CML patients with a median age at diagnosis of 11 years 9 months were enrolled in nine Italian centres. Complete cytogenetic response was achieved in 91.5% of the evaluable patients at a median time of 6 months. BCR-ABL1 International Scale ≤ 0.1% (major molecular response; MMR) and ≤0.01% (molecular response; MR) at 12 months were 66.6% and 33%, respectively. During follow-up, MMR and MR were achieved in 78.6% and 61% of children, respectively. IM was safely discontinued in 3 long-term treated children with a durable MR. Twelve patients (eight cytogenetic/molecular responders) underwent stem cell transplantation. The progression-free survival probabilities at 96 months for responding patients who continued IM and for those transplanted were 60% and 50%, respectively. After a median follow-up of 52 months (range 3-146), all patients are alive. High-dose IM is a long-term effective therapy in children and adolescents with CP-CML., (© 2015 John Wiley & Sons Ltd.)

Sporadic essential thrombocythaemia (ET) is rare in paediatrics, and the diagnostic and clinical approach to paediatric cases cannot be simply copied from experience with adults. Here, we assessed 89 children with a clinical diagnosis of ET and found that 23 patients (25·8%) had a clonal disease. The JAK2 V617F mutation was identified in 14 children, 1 child had the MPL W515L mutation, and 6 had CALR mutations. The monoclonal X-chromosome inactivation pattern was seen in six patients (two with JAK2 V617F and two with CALR mutations). The other 66 patients (74·2%) had persistent thrombocytosis with no clonality. There were no clinical or haematological differences between the clonal and non-clonal patients. The relative proportion of ET-specific mutations in the clonal children was much the same as in adults. The higher prevalence of non-clonal cases suggests that some patients may not have myeloproliferative neoplasms, with significant implications for their treatment., (© 2015 John Wiley & Sons Ltd.)