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Leukemia. 2018 Dec;32(12):2558-2571. doi: 10.1038/s41375-018-0268-9. Epub 2018 Oct 1.

Sequential high-dose cytarabine and mitoxantrone (S-HAM) versus standard double induction in acute myeloid leukemia-a phase 3 study.

Author information

1
Department of Oncology and Hematology, Hospital Barmherzige Brüder, Regensburg, Germany. Jan.Braess@barmherzige-regensburg.de.
2
Department of Medicine III, University Hospital LMU Campus Grosshadern, Munich, Germany. Jan.Braess@barmherzige-regensburg.de.
3
Insitute for Biostatistics and Clinical Research, University Hospital, Münster, Germany.
4
Friedrich Löffler Institute, Federal Research Centre, Greifswald-Insel Riems, Germany.
5
Department of Internal Medicine I, University Hospital, Cologne, Germany.
6
Department of Medicine III, University Hospital LMU Campus Grosshadern, Munich, Germany.
7
Department of Hematology and Oncology, Catholic Hospital, Hagen, Germany.
8
Department of Medicine III, University Hospital, Mannheim, Germany.
9
Department of Medicine I, Hospital Maria Hilf, Mönchengladbach, Germany.
10
Department of Hematology and Medical Oncology, St. Antonius Hospital, Eschweiler, Germany.
11
Department of Hematology and Oncology and Tumor Immunology, Helios Hospital, Berlin-Buch, Germany.
12
Department of Medicine I, University Hospital, Lübeck, Germany.
13
Department of Medicine I, Johanniter Hospital, Bonn, Germany.
14
Department of Medicine A, Klinikum Ludwigshafen, Ludwigshafen, Germany.
15
Department of Hematology, Oncology and Palliative Care, Vivantes Klinikum Neukölln, Berlin, Germany.
16
Department of Medicine, Vinzenz Pallotti Hospital, Bergisch-Gladbach, Germany.
17
Department of Hematology and Oncology, Klinikum Osnabrück, Osnabrück, Germany.
18
Department of Hematology and Oncology, St. Josef Hospital, Paderborn, Germany.
19
Department of Hematology and Oncology, Klinikum Harlaching, Munich, Germany.
20
Department of Hematology, Oncology and Palliative Care, Augusta Hospital, Bochum, Germany.
21
Department of Medicine I, Klinikum Frankfurt/Oder, Frankfurt/Oder, Germany.
22
Department of Hematology, Oncology and Palliative Care, Evangelisches Krankenhaus, Bielefeld, Germany.
23
Department of Medical Oncology, Radiooncology, Hematology and Palliative Care, St. Josef Hospital, Gelsenkirchen, Germany.
24
Department of Hematology and Oncology, Klinikum Idar-Oberstein, Idar-Oberstein, Germany.
25
Department of Medicine III, Klinikum Leverkusen, Leverkusen, Germany.
26
Department of Medicine, Vivantes Klinikum Spandau, Berlin, Germany.
27
Department of Medicine II, Klinikum Gütersloh, Gütersloh, Germany.
28
Department of Medicine I, St. Johannes Hospital, Dortmund, Germany.
29
Department for Bone Marrow and Blood Stem Cell Transplantation, DKD Deutsche Klinik für Diagnostik, Wiesbaden, Germany.
30
Department of Medicine I, Knappschaftskrankenhaus, Bottrop, Germany.
31
Division of Medical Informatics in Translational Oncology, DKFZ German Cancer Research Center, Heidelberg, Germany.
32
Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
33
Institute of Experimental Cancer Research, University Hospital, Ulm, Germany.
34
Department of Oncology and Hematology, Hospital Barmherzige Brüder, Regensburg, Germany.
35
German Society of Hematology and Oncology DGHO, Berlin, Germany.
36
Department of Bone Marrow Transplantation, University Hospital, Essen, Germany.

Abstract

Dose-dense induction with the S-HAM regimen was compared to standard double induction therapy in adult patients with newly diagnosed acute myeloid leukemia. Patients were centrally randomized (1:1) between S-HAM (2nd chemotherapy cycle starting on day 8 = "dose-dense") and double induction with TAD-HAM or HAM(-HAM) (2nd cycle starting on day 21 = "standard"). 387 evaluable patients were randomly assigned to S-HAM (N = 203) and to standard double induction (N = 184). The primary endpoint overall response rate (ORR) consisting of complete remission (CR) and incomplete remission (CRi) was not significantly different (P = 0.202) between S-HAM (77%) and double induction (72%). The median overall survival was 35 months after S-HAM and 25 months after double induction (P = 0.323). Duration of critical leukopenia was significantly reduced after S-HAM (median 29 days) versus double induction (median 44 days)-P < 0.001. This translated into a significantly shortened duration of hospitalization after S-HAM (median 37 days) as compared to standard induction (median 49 days)-P < 0.001. In conclusion, dose-dense induction therapy with the S-HAM regimen shows favorable trends but no significant differences in ORR and OS compared to standard double induction. S-HAM significantly shortens critical leukopenia and the duration of hospitalization by 2 weeks.

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