Results of a randomized trial in children with Acute Myeloid Leukaemia: medical research council AML12 trial.

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.

Prognostic factor analysis of the survival of elderly patients with AML in the MRC AML11 and LRF AML14 trials.

This analysis, of 2483 patients with acute myeloid leukaemia (AML) aged 60+ years entered into two UK trials, was performed to determine the baseline parameters related to survival and to develop a risk index. The Medical Research Council (MRC) AML11 trial (n = 1071) was used to develop the index; this was validated using data from the Leukaemia Research fund (LRF) AML14 trial on 1137 intensively (AML14I) and 275 non-intensively (AML14NI) treated patients. In AML11, cytogenetic group, age, white blood count, performance status and type of AML (de novo, secondary) were all highly significantly related to prognosis in multivariate analysis. The regression coefficients were used to define good, standard and poor risk groups, with 1-year survival of 53%, 43% and 16% respectively (P < 0.0001). The risk index showed very good discrimination in both AML14I and AML14NI (both P < 0.0001), thereby providing validation, although survival in all groups was very poor in AML14NI. The risk factors for survival in older AML patients were similar to those in younger ones and discrimination of patient groups with relatively good to very poor prognosis was possible. These risk groups apply to both intensively and non-intensively treated patients. Randomized trials of intensive versus non-intensive therapy are needed to determine which types of patient should be given which type of treatment.

Hyperfractionated Accelerated Radiotherapy (HART) with maintenance chemotherapy for metastatic (M1-3) Medulloblastoma--a safety/feasibility study.

BACKGROUND AND PURPOSE: To evaluate feasibility and toxicity of Hyperfractionated Accelerated Radiotherapy (HART) 1.24Gy b.i.d. followed by chemotherapy for M1-3 Medulloblastoma (MB). The aim of HART was to use hyperfractionation to improve therapeutic ratio combined with acceleration to minimise tumour cell repopulation during radiotherapy (RT). MATERIALS AND METHODS: Between February 2002 and May 2008, 34 eligible patients (22 male, 12 female) aged 3-15years (median 7) with metastatic MB (M1-9; M2-3, M3-22) received HART with a craniospinal radiotherapy (CSRT) dose of 39.68Gy followed by 22.32Gy boost to the whole posterior fossa and 9.92Gy metastatic boosts. The 8th and subsequent patients received vincristine (VCR) 1.5mg/m(2) weekly×8 doses over 8weeks starting during the 1st week of RT. Maintenance chemotherapy comprised 8 six-weekly cycles of VCR 1.5mg/m(2) weekly×3, CCNU 75mg/m(2) and cisplatin 70mg/m(2). RESULTS: Median duration of HART was 34days (range 31-38). Grade 3-4 toxicities included mucositis (8), nausea (10), anaemia (5), thrombocytopaenia (2), leucopaenia (24). With 4.5-year median follow-up, 3-year EFS and OS were 59% and 71%, respectively. Of 10 relapses, 1 was outside the central nervous system (CNS), 1 posterior fossa alone and 8 leptomeningeal with 3 also associated with posterior fossa. CONCLUSION: HART with or without VCR was well tolerated and may have a place in the multi-modality management of high-risk MB.