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Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial.

Burnett, Alan K and Russell, Nigel H and Hills, Robert K and Hunter, Ann E and Kjeldsen, Lars and Yin, John and Gibson, Brenda E S and Wheatley, Keith and Milligan, Donald (2013) Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 31 (27). pp. 3360-8. ISSN 1527-7755. This article is accessible to all HEFT staff and students via NHS Evidence www.evidence.nhs.uk by using their HEFT Athens login IDs

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Official URL: http://jco.ascopubs.org/content/31/27/3360.long

Abstract

PURPOSE

Treatment outcomes in younger patients with acute myeloid leukemia (AML) have improved, but optimization and new combinations are needed. We assess three combinations in induction and consolidation.

PATIENTS AND METHODS

Younger untreated patients with AML (median age, 49 years; range, 0 to 73 years) were randomly allocated to two induction courses of daunorubicin and cytarabine (DA) with or without etoposide (ADE; n = 1983) or ADE versus fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-Ida; n = 1268), and to amsacrine, cytarabine, etoposide, and then mitoxantrone/cytarabine (MACE-MidAC) or high-dose cytarabine (n = 1,445) 3 g/m(2) or 1.5 g/m(2) (n = 657) in consolidation, and finally to a fifth course (cytarabine) or not (n = 227).

RESULTS

Overall remission rates were similar for DA versus ADE (84% v 86%; P = .14) and ADE versus FLAG-Ida (86% v 85%; P = .7), with more course 1 remissions after FLAG-Ida (77%) reducing relapse (38% v 55%; P < .001) and improving relapse-free survival (45% v 34%; P = .01), overall and in subgroups, but with increased myelosuppression, reducing participation in the consolidation randomization. Overall outcomes were similar between MACE/MidAc and high-dose cytarabine (1.5/3.0 g/m(2)), but cytarabine required less supportive care. MACE/MidAc was superior for high-risk patients. A fifth course provided no benefit. The outcome for recipients of only two FLAG-Ida courses were not different from that with DA/ADE with consolidation.

CONCLUSION

FLAG-Ida is an effective remission induction treatment, with a high complete remission rate after course 1 and reduced relapse. Consolidation with MACE/MidAc is similar overall to high-dose cytarabine, but superior in high-risk patients. Cytarabine at 1.5 g/m(2) is equivalent to a 3 g/m(2) dose. A fifth course is unnecessary. In patients receiving FLAG-Ida (two courses) and cytarabine (two courses), 8-year survival was 63% for patients with intermediate-risk and 95% for those with favorable-risk disease.

Item Type: Article
Additional Information: This article is accessible to all HEFT staff and students via NHS Evidence www.evidence.nhs.uk by using their HEFT Athens login IDs
Subjects: QZ Pathology. Oncology
Divisions: Planned IP Care > Oncology and Clinical Haematology
Related URLs:
Depositing User: Mrs Caroline Tranter
Date Deposited: 03 Feb 2015 13:50
Last Modified: 03 Feb 2015 13:50
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/779

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