1. ¹Department of Internal Medicine III, University of Ulm, Ulm, Germany
2. ²Department of Internal Medicine I, University of Homburg, Germany
3. ³Städtisches Klinikum, Karlsruhe, Germany
4. ⁴Department of Internal Medicine I, University of Bonn, Germany
5. ⁵Klinikum Oldenburg, Germany
6. ⁶Klinikum Stuttgart, Germany
7. ⁷Department of Internal Medicine III, Technical University of Munich, Germany
8. ⁸Städtisches Krankenhaus München-Schwabing, Munich, Germany
9. ⁹Department of Internal Medicine, University of Kiel, Germany
10. ¹⁰Department of Internal Medicine IV, University of Giessen, Germany
11. ¹¹Department of Internal Medicine V, University of Heidelberg, Germany
12. ¹²Hanusch-Krankenhaus, Wien, Austria
13. ¹³Krankenhaus der Barmherzigen Brüder, Trier, Germany
14. ¹⁴Caritas-Klinik St Theresia, Saarbrücken, Germany
15. ¹⁵Allgemeines Krankenhaus Altona, Hamburg, Germany
16. ¹⁶Kreiskrankenhaus, Trostberg, Germany
17. ¹⁷Caritas Krankenhaus, Lebach, Germany
18. ¹⁸Department of Internal Medicine, University of Göttingen, Germany
19. ¹⁹Central Unit of Biostatistics, German Cancer Research Center, Heidelberg, Germany
20. ²⁰Department of Hematology, University of Düsseldorf, Germany

Correspondence: Dr RF Schlenk, Department of Internal Medicine III, University Hospital of Ulm, Robert-Koch-Strasse 8, 89081 Ulm, Germany. Fax: +49 731 50024405; E-mail: Richard.Schlenk@medizin.uni-ulm.de

Received 17 February 2004; Accepted 11 August 2004; Published online 23 September 2004.

Abstract

The purpose of our study was (i) to evaluate the impact of all-trans retinoic acid (ATRA) given as adjunct to chemotherapy and (ii) to compare second consolidation vs maintenance therapy in elderly patients with acute myeloid leukemia (AML). A total of 242 patients aged 61 years (median, 66.6 years) with AML were randomly assigned to ATRA beginning on day +3 after the initiation of chemotherapy (ATRA-arm, n=122) or no ATRA (standard-arm, n=120) in combination with induction and first consolidation therapy. A total of 61 patients in complete remission (CR) were randomly assigned to second intense consolidation (n=31) or 1-year oral maintenance therapy (n=30). After induction therapy the intention-to-treat analysis revealed a significant difference in CR rates between the ATRA- and the standard-arm (52 vs 39%; P=0.05). Event-free (EFS) and overall survival (OS) were significantly better in the ATRA-compared to the standard-arm (P=0.03 and 0.01, respectively). OS after second randomization was significantly better for patients assigned to intensive consolidation therapy (P<0.001). The multivariate model for survival revealed lactate dehydrogenase, cytogenetic risk group, age, and first and second randomization as prognostic variables. In conclusion, the addition of ATRA to induction and consolidation therapy may improve CR rate, EFS and OS in elderly patients with AML.