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6-Thioguanine, Cytarabine, and Daunorubicin (TAD) and High-Dose Cytarabine and Mitoxantrone (HAM) for Induction, TAD for Consolidation, and Either Prolonged Maintenance by Reduced Monthly TAD or TAD-HAM-TAD and One Course of Intensive Consolidation by Sequential HAM in Adult Patients at All Ages With De Novo Acute Myeloid Leukemia (AML): A Randomized Trial of the German AML Cooperative Group

Thomas Büchner, Wolfgang Hiddemann, Wolfgang E. Berdel, Bernhard Wörmann, Claudia Schoch, Christa Fonatsch, Helmut Löffler, Torsten Haferlach, Wolf-Dieter Ludwig, Georg Maschmeyer, Peter Staib, Carlo Aul, Andreas Grüneisen, Eva Lengfelder, Norbert Frickhofen, Wolfgang Kern, Hubert L. Serve, Rolf M. Mesters, Maria Cristina Sauerland, Achim Heinecke

From the Department of Medicine, Hematology/Oncology, University of Münster, Münster, Germany.

Address reprint requests to Thomas Büchner, MD, PhD, University Medical Center, Department of Medicine, Hematology and Oncology, Albert-Schweitzer-Str 33, D-48129 Münster, Germany; e-mail: buechnr{at}uni-muenster.de.

Purpose: To examine the efficacy of prolonged maintenance chemotherapy versus intensified consolidation therapy for patients with acute myeloid leukemia (AML).

Materials and Methods: Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were randomly assigned to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m² [age < 60 years] or 1 g/m² [age 60 years] x 6) induction, TAD consolidation, and monthly modified TAD maintenance for 3 years, or TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m² (age < 60 years) or 0.5 g/m² (age 60 years) x 8 instead of maintenance.

Results: A total of 69.2% patients went into complete remission (CR). Median relapse-free survival (RFS) was 19 months for patients on the maintenance arm, with 31.4% of patients relapse-free at 5 years, versus 12 months for patients on the S-HAM arm, with 24.7% of patients relapse-free at 5 years (P = .0118). RFS from maintenance was superior in patients with poor risk by unfavorable karyotype, age 60 years, lactate dehydrogenase level greater than 700 U/L, or day 16 bone marrow blasts greater than 40% (P = .0061) but not in patients with good risk by complete absence of any poor risk factors. Although a survival benefit in the CR patients is not significant (P = .085), more surviving patients in the maintenance than in the S-HAM arm remain in first CR (P = .026).

Conclusion: We conclude that TAD-HAM-TAD-maintenance first-line treatment has a higher curative potential than TAD-HAM-TAD-S-HAM and improves prognosis even among patients with poor prognosis.

Supported by Deutsche Krebshilfe, Bonn, Germany, grant no. M 17/92/Bü 1.

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