title: Results of a randomized trial in children with Acute Myeloid Leukaemia: medical research council AML12 trial.
abstract: The Medical Research Council Acute Myeloid Leukaemia 12 (MRC AML12) trial (children) addressed the optimal anthracenedione/anthracycline in induction and the optimal number of courses of consolidation chemotherapy. 504 children (<16 years) with AML were randomized between mitoxantrone/cytarabine/etoposide or daunorubicin/cytarabine/etoposide as induction chemotherapy and 270 entered a second randomization between a total of four or five courses of treatment. Ten-year event-free (EFS) and overall survival (OS) was 54% and 63% respectively; the relapse rate was 35%. There was no difference in complete remission rate between the induction regimens, but there was a benefit for mitoxantrone with regard to relapse rate [32% vs. 39%; Hazard ratio (HR) 0·73; 95% confidence interval (CI) 0·54, 1·00] and disease-free survival (DFS; 63% vs. 55%; HR 0·72; 95% CI 0·54, 0·96). However, this did not translate into a better EFS or OS (HR 0·84; 95% CI 0·63, 1·12). Results of the second randomization did not show a survival benefit for a fifth course of treatment (HR 1·01; 95% CI 0·63, 1·62), suggesting a ceiling of benefit for conventional chemotherapy and demonstrating the need for new agents. EFS was superior compared to the preceding trial AML10, partly due to fewer deaths in remission, highlighting the importance of supportive care.
authors: Department of Haematology, Royal Hospital for Sick Children, Glasgow G3 8SJ, Scotland, UK. brenda.gibson@ggc.scot.nhs.uk
authors: Brenda E S
authors: BE
authors: Gibson
authors: David K H
authors: DK
authors: Webb
authors: Andrew J
authors: AJ
authors: Howman
authors: Siebold S N
authors: SS
authors: De Graaf
authors: Christine J
authors: CJ
authors: Harrison
authors: Keith
authors: K
authors: Wheatley
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D060830:Consolidation Chemotherapy; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage; D011379:Prognosis; D016019:Survival Analysis; D013866:Thioguanine / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D005047:Etoposide; D008942:Mitoxantrone; D013866:Thioguanine; D003630:Daunorubicin