Long-term results of a prospective randomized trial evaluating G-CSF priming in intensive induction chemotherapy followed by autologous stem cell transplantation in elderly patients with acute myeloid leukemia
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Few studies have evaluated granulocyte colony-stimulating factor (G-CSF) priming in elderly patients with intensively treated acute myeloid leukemia (AML), and no data are available for genetically defined AML subgroups. We provide long-term results (median follow-up 7.6 years) of a randomized trial in which 183 patients (median age 67 years) received G-CSF prior to (G-CSF priming) or after two cycles of induction chemotherapy. CR rates with G-CSF priming and G-CSF post-chemotherapy were comparable (57 vs. 67 %, p = 0.153), with overall survival (OS) probabilities of 14 vs. 17 % at 10 years. Induction mortality was significantly higher with G-CSF priming (23 vs. 10 %, p = 0.015), primarily in normal karyotype (NK) AML. In this subgroup, a trend for better relapse-free survival (RFS) was observed with G-CSF priming (44 vs. 22 % at 10 years, p = 0.074) but did not translate into an OS benefit. G-CSF priming had no impact on AML with FLT3-ITD and NPM mutations and did not improve outcome in patients with adverse cytogenetics. In a landmark analysis, late consolidation with autologous stem cell transplantation or a second consolidation cycle significantly improved RFS compared with one consolidation cycle (21.0 vs. 12.8 months, p = 0.046). Future studies on G-CSF priming should be restricted to NK AML and used only in post-remission therapy.
KeywordsAcute myeloid leukemia G-CSF priming Monosomal karyotype FLT3-ITD Autologous stem cell transplantation
The authors would like to thank Caroline Zander, Gabriele Samson, and Emilia Januschewski for the excellent data management. This study was supported by an unrestricted grant from Amgen GmbH and Pfizer GmbH by the Deutsche Krebshilfe e.V (grant no. 109003) and grant no. DJCLS R 10/22 from the Deutsche-José-Carreras Leukämie-Stiftung e.V (DJCLS). OGO holds an endowed professorship of the DJCLS.
Conflict of interest
The authors declare no conflict of interest.
Informed consent was obtained from all patients for being included in the study.
- 5.Braess J, Voss S, Jahns-Streubel G, Schoch C, Haferlach T, Kern W et al (2000) The pharmacodynamic basis for the increased antileukaemic efficacy of cytosine arabinoside-based treatment regimens in acute myeloid leukaemia with a high proliferative activity. Br J Haematol 110:170–179PubMedCrossRefGoogle Scholar
- 10.Estey EH, Thall PF, Pierce S, Cortes J, Beran M, Kantarjian H et al (1999) Randomized phase II study of fludarabine + cytosine arabinoside + idarubicin +/− all-trans retinoic acid +/− granulocyte colony-stimulating factor in poor prognosis newly diagnosed acute myeloid leukemia and myelodysplastic syndrome. Blood 93:2478–2484PubMedGoogle Scholar
- 11.Amadori S, Suciu S, Jehn U, Stasi R, Thomas X, Marie JP et al (2005) Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study. Blood 106:27–34PubMedCrossRefGoogle Scholar
- 12.Ohno R, Naoe T, Kanamaru A, Yoshida M, Hiraoka A, Kobayashi T et al (1994) A double-blind controlled study of granulocyte colony-stimulating factor started two days before induction chemotherapy in refractory acute myeloid leukemia. Kohseisho Leukemia Study Group. Blood 83:2086–2092PubMedGoogle Scholar
- 15.Milligan DW, Wheatley K, Littlewood T, Craig JI, Burnett AK (2006) Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial. Blood 107:4614–4622PubMedCrossRefGoogle Scholar
- 17.Mitelman F (1995) An international system for human cytogenetic nomenclature. S. Karger, BaselGoogle Scholar
- 20.Frohling S, Schlenk RF, Breitruck J, Benner A, Kreitmeier S, Tobis K et al (2002) Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood 100:4372–4380PubMedCrossRefGoogle Scholar
- 24.Krug U, Rollig C, Koschmieder A, Heinecke A, Sauerland MC, Schaich M et al (2010) Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes. Lancet 376:2000–2008PubMedCrossRefGoogle Scholar
- 26.Thomas X, Raffoux E, Botton S, Pautas C, Arnaud P, de Revel T et al (2007) Effect of priming with granulocyte-macrophage colony-stimulating factor in younger adults with newly diagnosed acute myeloid leukemia: a trial by the Acute Leukemia French Association (ALFA) Group. Leukemia 21:453–461PubMedCrossRefGoogle Scholar
- 27.Cahn JY, Labopin M, Mandelli F, Goldstone AH, Eberhardt K, Reiffers J et al (1995) Autologous bone marrow transplantation for first remission acute myeloblastic leukemia in patients older than 50 years: a retrospective analysis of the European Bone Marrow Transplant Group. Blood 85:575–579PubMedGoogle Scholar
- 31.Ferrara F, Palmieri S, Annunziata M, Viola A, Pocali B, Califano C et al (2004) Continuous infusion idarubicin and oral busulfan as conditioning for patients with acute myeloid leukemia aged over 60 years undergoing autologous stem cell transplantation. Bone Marrow Transplant 34:573–576PubMedCrossRefGoogle Scholar
- 32.Thomas X, Suciu S, Rio B, Leone G, Broccia G, Fillet G et al (2007) Autologous stem cell transplantation after complete remission and first consolidation in acute myeloid leukemia patients aged 61–70 years: results of the prospective EORTC-GIMEMA AML-13 study. Haematologica 92:389–396PubMedCrossRefGoogle Scholar