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

被引：20

作者：

Braess, Jan ^{[1
,2
]}

Amler, Susanne ^{[3
,4
]}

Kreuzer, Karl-Anton ^{[5
]}

Spiekermann, Karsten ^{[2
]}

Lindemann, Hans Walter ^{[6
]}

Lengfelder, Eva ^{[7
]}

Graeven, Ullrich ^{[8
]}

Staib, Peter ^{[9
]}

Ludwig, Wolf-Dieter ^{[10
]}

Biersack, Harald ^{[11
]}

Ko, Yon-Dschun ^{[12
]}

Uppenkamp, Michael J. ^{[13
]}

De Wit, Maike ^{[14
]}

Korsten, Stefan ^{[15
]}

Peceny, Rudolf ^{[16
]}

Gaska, Tobias ^{[17
]}

Schiel, Xaver ^{[18
]}

Behringer, Dirk M. ^{[19
]}

Kiehl, Michael G. ^{[20
]}

Zinngrebe, Bettina ^{[21
]}

Meckenstock, Gerald ^{[22
]}

Roemer, Eva ^{[23
]}

Medgenberg, Dirk ^{[24
]}

Spaeth-Schwalbe, Ernst ^{[25
]}

Massenkeil, Gero ^{[26
]}

Hindahl, Heidrun ^{[27
]}

Schwerdtfeger, Rainer ^{[28
]}

Trenn, Guido ^{[29
]}

Sauerland, Cristina ^{[3
]}

Koch, Raphael ^{[3
]}

Lablans, Martin ^{[3
,30
]}

Faldum, Andreas ^{[3
]}

Goerlich, Dennis ^{[3
]}

Bohlander, Stefan K. ^{[2
,31
]}

Schneider, Stephanie ^{[2
]}

Dufour, Annika ^{[2
]}

Buske, Christian ^{[2
,32
]}

Fiegl, Michael ^{[2
]}

Subklewe, Marion ^{[2
]}

Braess, Birgit ^{[1
,2
]}

Unterhalt, Michael ^{[2
]}

Baumgartner, Anja ^{[2
]}

Woermann, Bernhard ^{[33
]}

Beelen, Dietrich ^{[34
]}

Hiddemann, Wolfgang ^{[2
]}

机构：

[1] Hosp Barmherzige Bruder, Dept Oncol & Hematol, Regensburg, Germany

[2] Univ Hosp, Dept Med 3, LMU Campus, Munich, Germany

[3] Univ Hosp, Inst Biostat & Clin Res, Munster, Germany

[4] Fed Res Ctr, Friedrich Loffler Inst, Greifswald, Germany

[5] Univ Hosp, Dept Internal Med 1, Cologne, Germany

[6] Catholic Hosp, Dept Hematol & Oncol, Hagen, Germany

[7] Univ Hosp, Dept Med 3, Mannheim, Germany

[8] Hosp Maria Hilf, Dept Med 1, Monchengladbach, Germany

[9] St Antonius Hosp, Dept Hematol & Med Oncol, Eschweiler, Germany

[10] Helios Hosp, Dept Hematol & Oncol & Tumor Immunol, Berlin, Germany

[11] Univ Hosp, Dept Med 1, Lubeck, Germany

[12] Johanniter Hosp, Dept Med 1, Bonn, Germany

[13] Klinikum Ludwigshafen, Dept Med A, Ludwigshafen, Germany

[14] Vivantes Klinikum Neukolln, Dept Hematol Oncol & Palliat Care, Berlin, Germany

[15] Vinzenz Pallotti Hosp, Dept Med, Bergisch Gladbach, Germany

[16] Klinikum Osnabruck, Dept Hematol & Oncol, Osnabruck, Germany

[17] St Josef Hosp, Dept Hematol & Oncol, Paderborn, Germany

[18] Klinikum Harlaching, Dept Hematol & Oncol, Munich, Germany

[19] Augusta Hosp, Dept Hematol Oncol & Palliat Care, Bochum, Germany

[20] Klinikum Frankfurt Oder, Dept Med 1, Frankfurt, Germany

[21] Evangel Krankenhaus, Dept Hematol Oncol & Palliat Care, Bielefeld, Germany

[22] St Josef Hosp, Dept Med Oncol Radiooncol Hematol & Palliat Care, Gelsenkirchen, Germany

[23] Klinikum Idar Oberstein, Dept Hematol & Oncol, Idar Oberstein, Germany

[24] Klinikum Leverkusen, Dept Med 3, Leverkusen, Germany

[25] Vivantes Klinikum Spandau, Dept Med, Berlin, Germany

[26] Klinikum Gutersloh, Dept Med 2, Gutersloh, Germany

[27] St Johannes Hosp, Dept Med 1, Dortmund, Germany

[28] Deutsch Klin Diagnost, Dept Bone Marrow & Blood Stem Cell Transplantat, Wiesbaden, Germany

[29] Knappschaftskrankenhaus, Dept Med 1, Bottrop, Germany

[30] DKFZ German Canc Res Ctr, Div Med Informat Translat Oncol, Heidelberg, Germany

[31] Univ Auckland, Dept Mol Med & Pathol, Auckland, New Zealand

[32] Univ Hosp, Inst Expt Canc Res, Ulm, Germany

[33] German Soc Hematol & Oncol DGHO, Berlin, Germany

[34] Univ Hosp, Dept Bone Marrow Transplantat, Essen, Germany

来源：

LEUKEMIA | 2018年 / 32卷 / 12期

关键词：

CYTOSINE-ARABINOSIDE; CRITICAL NEUTROPENIA; SALVAGE THERAPY; ADULTS; DIAGNOSIS; AML; TRANSPLANTATION; RECOMMENDATIONS; CONSOLIDATION; CHEMOTHERAPY;

D O I：

10.1038/s41375-018-0268-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：2558 / 2571

页数：14

共 19 条

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