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Blood, 15 January 2005, Vol. 105, No. 2, pp. 481-488.
Prepublished online as a Blood First Edition Paper on June 22, 2004; DOI 10.1182/blood-2004-01-0326.


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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine

Kenneth F. Bradstock, Jane P. Matthews, Raymond M. Lowenthal, Heather Baxter, John Catalano, Timothy Brighton, Devinder Gill, Paul Eliadis, Douglas Joshua, Paul Cannell, Anthony P. Schwarer, Simon Durrant, Anne Gillett, Jerry Koutts, Kerry Taylor, John Bashford, Christopher Arthur, Arno Enno, Lindsay Dunlop, Jeff Szer, Michael Leahy, Surender Juneja, and Graham A. R. Young, for the Australasian Leukaemia and Lymphoma Group

From the Department of Haematology, Westmead Hospital, Westmead, NSW, Australia; Statistical Centre, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Royal Hobart Hospital, Hobart, TAS, Australia; Monash Medical Centre, Clayton, VIC, Australia; St George Hospital, Kogarah, NSW, Australia; Princess Alexandra Hospital, Woolloongabba, QLD, Australia; Wesley Medical Centre, Brisbane, QLD, Australia; Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Royal Perth Hospital, Perth, WA, Australia; Alfred Hospital, Prahran, VIC, Australia; Royal Brisbane Hospital, Herston, QLD, Australia; Mater Hospital, South Brisbane, QLD, Australia; Royal North Shore Hospital, St Leonards, NSW, Australia; Mater Hospital, Newcastle, NSW, Australia; Liverpool Hospital, Liverpool, NSW, Australia; Royal Melbourne Hospital, Melbourne VIC, Australia; and Fremantle Hospital, Fremantle, WA, Australia.

The value of administering sequential courses of chemotherapy containing high-dose cytarabine in both induction and consolidation therapy for acute myeloid leukemia (AML) has not been assessed in a prospective randomized trial. Two hundred ninety-two AML patients aged 15 to 60 years were enrolled in the Australasian Leukaemia and Lymphoma Group (ALLG) AML trial number 7 (M7) protocol to evaluate this question. All received induction therapy with the ICE protocol (idarubicin 9 mg/m2 x 3; cytarabine 3 g/m2 twice a day on days 1, 3, 5, 7; etoposide 75 mg/m2 x 7). Complete remission was achieved in 234 (80%) patients. Two hundred two patients in remission were then randomized to either a further identical cycle of ICE or 2 attenuated courses (cytarabine 100 mg/m2 daily x 5, idarubicin x 2, etoposide x 5 [IcE]). ICE consolidation therapy was more toxic than IcE, however, the treatment-related death rate was not significantly different. There was no difference between the 2 consolidation arms for relapse-free survival at 3 years (49% for ICE vs 46% for IcE; P = .66), survival following randomization (61% vs 62%; P = .91), or the cumulative incidence of relapse (43% vs 51%; P = .31), and there was no difference within cytogenetic risk groups. Intensive induction chemotherapy incorporating high-dose cytarabine results in high complete remission rates, but further intensive consolidation treatment does not appear to confer additional benefit.


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