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. Tenyear 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) 0AE73; 95% confidence interval (CI) 0AE54, 1AE00] and disease-free survival (DFS; 63% vs. 55%; HR 0AE72; 95% CI 0AE54, 0AE96). However, this did not translate into a better EFS or OS (HR 0AE84; 95% CI 0AE63, 1AE12). Results of the second randomization did not show a survival benefit for a fifth course of treatment (HR 1AE01; 95% CI 0AE63, 1AE62), 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.

Effectiveness of supportive care measures to reduce infections in pediatric AML: a report from the Children’s Oncology Group

“…Therapy consisted of 5 cycles of intensive chemotherapy based on the UK Medical Research Council 12 study, 10 and patients were randomized to receive or not receive gemtuzumab ozogamicin (GMTZ) at 3 mg/kg per dose once on day 6 during induction I and intensification II. Induction I consisted of cytarabine 100 mg/m 2 per dose intravenously every 12 hours on days 1 through 10; daunorubicin 50 mg/m 2 per dose intravenously on days 1, 3, and 5; and etoposide 100 mg/m 2 per dose intravenously daily on days 1 through 5 (ara-C, daunorubicin, etoposide 10 1 3 1 5).…”

Dose-related efficacy and toxicity of gemtuzumab ozogamicin in pediatric acute myeloid leukemia

“…Unfortunately, one-third of the patients eventually relapse [1][2][3][4][5][6][7][8]. Over the past years, new therapies have been designed to improve the prognosis in AML including the development of antigen-targeted therapies.…”

Outcomes of allogeneic stem cell transplantation among patients with acute myeloid leukemia presenting active disease: Experience of a single European Comprehensive Cancer Center

“…3,5,6 Recent results from clinical trials indicate a 1-year overall survival (OS) rate of 60 to 70%. [7][8][9] In children with AML who relapsed post-ASCT and after a second ASCT, it was reported at approximately 30 to 40% by Lee et al 9 In 2013, survival outcomes were reported to be similar between adolescents and children with AML following ASCT. 10 Myeloablative preparative regimen used for ASCT induces profound neutropenia and platelet decrease.…”