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Double Induction Containing Either Two Courses or One Course of High-Dose Cytarabine Plus Mitoxantrone and Postremission Therapy by Either Autologous Stem-Cell Transplantation or by Prolonged Maintenance for Acute Myeloid Leukemia

Thomas Büchner, Wolfgang E. Berdel, Claudia Schoch, Torsten Haferlach, Hubert L. Serve, Joachim Kienast, Susanne Schnittger, Wolfgang Kern, Joelle Tchinda, Albrecht Reichle, Eva Lengfelder, Peter Staib, Wolf-Dieter Ludwig, Carlo Aul, Hartmut Eimermacher, Leopold Balleisen, Maria-Cristina Sauerland, Achim Heinecke, Bernhard Wörmann, Wolfgang Hiddemann

From the Department of Medicine, Hematology and Oncology, the Department of Human Genetics, and the Department of Medical Informatics and Biomathematics, University of Muenster, Muenster; Department of Hematology and Oncology, University of Regensburg, Regensburg; Department of Hematology and Oncology, University of Heidelberg, Mannheim; Department of Hematology and Oncology, University of Cologne, Cologne; and Department of Hematology and Oncology, University of Berlin, Berlin; Department of Hematology and Oncology, St Johannes Hospital, Duisburg; Catholic Hospital, Hagen; and Evangelian Hospital, Hamm; Department of Hematology and Oncology, Municipal Medical Centre, Braunschweig, Braunschweig; Department of Internal Medicine III, University of Munich, Munich; and the Clinical Cooperative Group Acute Leukemias of the National Center for Environment and Health, Munich, Germany

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

PURPOSE: Intensification by high-dose cytarabine in postremission or induction therapy and prolonged maintenance are established strategies to improve the outcome in patients with acute myeloid leukemia (AML). Whether additional intensification can add to this effect has not yet been determined.

PATIENTS AND METHODS: A total of 1,770 patients (age 16 to 85 years) with de novo or secondary AML or high-risk myelodysplastic syndrome (MDS) were randomly assigned upfront for induction therapy containing one course with standard dose and one course with high-dose cytarabine, or two courses with high-dose cytarabine, and in the same step received postremission prolonged maintenance or busulfan/cyclophosphamide chemotherapy with autologous stem-cell transplantation.

RESULTS: The complete remission rate in patients younger than 60 and 60 years of age was 70% and 53%, respectively. The overall survival at 3 years in the two age groups was 42% and 19%, the relapse-free survival was 40% and 19%, and the ongoing remission duration was 48% and 22%, respectively. There were no significant differences in these results between the two randomized induction arms or between the two postremission therapy arms. There was no significant difference in any prognostic subgroup according to secondary AML/MDS, cytogenetics, WBC, lactate dehydrogenase, and early blast clearance.

CONCLUSION: The regimen of one course with standard-dose cytarabine and one course with high-dose cytarabine for induction, and prolonged maintenance for postremission chemotherapy in patients with AML is not improved by additional escalation in cytotoxic treatment.

Supported by Grants No. M17/92/Bü1 and 70-2839-Bü4 from Deutsche Krebshilfe, 01 GI 9976 from BMBF Competence Network Acute and Chronic Leukemias, LSH-2002-2.2.0-3 European LeukemiaNet from European Commission, and an unrestricted grant from AMGEN.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Related Correspondence

• Problems With Up-Front Randomization in Clinical Trials
  Keith Wheatley, Robert K. Hills, and Alan K. Burnett
  JCO 2006 24: 5471-5472 [Full Text]

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