1

Supplementary Table 1: Studies and their full citations for the articles included in the meta-analysis

First Author* / Year / No. CSF / No. Control / AML
Type / CSF Type / Day CSF Initiation+ / Elderly++
Buchner(1) / 1993 / 36 / 31 / de novo / GM-CSF / -1 / Yes
Ohno(2) / 1994 / 28 / 30 / rel / G-CSF / -2 / Yes
Rottmann(3) / 1994 / 40 / 32 / de novo / GM-CSF / -1 / Yes
Hansen(4) / 1995 / 10 / 8 / de novo, rel / GM-CSF / -1 / Yes
Heil(5) / 1995 / 41 / 39 / de novo / GM-CSF / -2 / Yes
Zittoun(6) / 1996 / 50 / 53 / de novo / GM-CSF / -1 / No
Lowenberg(7) / 1997 / 138 / 136 / de novo / GM-CSF / -1 / NA
Lowenberg(8) / 1997 / 157 / 161 / de novo, 2° / GM-CSF / -1 / Yes
Witz(9) / 1998 / 114 / 126 / de novo / GM-CSF / 0 / Yes
Estey(10) / 1999 / 107 / 108 / de novo, rel, 2° / G-CSF / -1 / Yes
Hast(11) / 2003 / 46 / 47 / 2° / GM-CSF / -2 / Yes
Lowenberg(12) / 2003 / 321 / 319 / de novo, 2° / G-CSF / -1 / No
Buchner(13) / 2004 / 466 / 429 / NA / G-CSF / -2 / Yes
Bug(14) / 2006 / 91 / 92 / de novo, 2° / G-CSF / -1 / Yes
Lofgren(15) / 2004 / 55 / 55 / de novo / GM-CSF / -1 / Yes
Rowe(16) / 2004 / 113 / 125 / de novo / GM-CSF / -2 / Yes
Amadori (17) / 2005 / 360 / 362 / de novo, 2° / G-CSF / 0 / Yes
Milligan(18) / 2006 / 178 / 178 / de novo, rel, 2° / G-CSF / 0 / Yes
Thomas(19) / 2007 / 124 / 135 / de novo / GM-CSF / 0 / No

Abbreviations: AML – acute myeloid leukemia; rel - relapsed; 2° - secondary; G-CSF – granulocyte colony-stimulating factor; GM-CSF – granulocyte-macrophage colony-stimulating factor, CSF – colony-stimulating factor; NA – not available

* Reference number in the bibliography; + Number of days prior to initiation of chemotherapy; ++ Indicates whether elderly patients were included in the trial

Appendix References:

1.Buchner T, Hiddemann W, Wormann B, Rottmann R, Maschmeyer G, Ludwig WD, et al. The role of GM-CSF in the treatment of acute myeloid leukemia. Leukemia & lymphoma 1993; 11 Suppl 2: 21-24.

2.Ohno R, Naoe T, Kanamaru A, Yoshida M, Hiraoka A, Kobayashi T, et al. 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 1994 Apr 15; 83(8): 2086-2092.

3.Rottmann R, Buchner T, Hiddemann W, Wormann B, Maschmeyer G, Ludwig WD, et al. GM-CSF Multiple Course Priming and Long-Term Administration in Newly Diagnosed Acute Myeloid Leukemia: Comparison of Three Different GM-CSF Routes and Schedules with No GM-CSF. Onkologie 1994; (17): 58-61.

4.Hansen PB, Johnsen HE, Jensen L, Gaarsdal E, Simonsen K, Ralfkiaer E. Priming and treatment with molgramostim (rhGM-CSF) in adult high-risk acute myeloid leukemia during induction chemotherapy: a prospective, randomized pilot study. European journal of haematology 1995 May; 54(5): 296-303.

5.Heil G, Chadid L, Hoelzer D, Seipelt G, Mitrou P, Huber C, et al.GM-CSF in a double-blind randomized, placebo controlled trial in therapy of adult patients with de novo acute myeloid leukemia (AML). Leukemia 1995 Jan; 9(1): 3-9.

6.Zittoun R, Suciu S, Mandelli F, de Witte T, Thaler J, Stryckmans P, et al. Granulocyte-macrophage colony-stimulating factor associated with induction treatment of acute myelogenous leukemia: a randomized trial by the European Organization for Research and Treatment of Cancer Leukemia Cooperative Group. J Clin Oncol 1996 Jul; 14(7): 2150-2159.

7.Lowenberg B, Boogaerts MA, Daenen SM, Verhoef GE, Hagenbeek A, Vellenga E, et al.Value of different modalities of granulocyte-macrophage colony-stimulating factor applied during or after induction therapy of acute myeloid leukemia. J Clin Oncol 1997 Dec; 15(12): 3496-3506.

8.Lowenberg B, Suciu S, Archimbaud E, Ossenkoppele G, Verhoef GE, Vellenga E, et al.Use of recombinant GM-CSF during and after remission induction chemotherapy in patients aged 61 years and older with acute myeloid leukemia: final report of AML-11, a phase III randomized study of the Leukemia Cooperative Group of European Organisation for the Research and Treatment of Cancer and the Dutch Belgian Hemato-Oncology Cooperative Group. Blood 1997 Oct 15; 90(8): 2952-2961.

9.Witz F, Sadoun A, Perrin MC, Berthou C, Briere J, Cahn JY, et al. A placebo-controlled study of recombinant human granulocyte-macrophage colony-stimulating factor administered during and after induction treatment for de novo acute myelogenous leukemia in elderly patients. Groupe Ouest Est Leucemies Aigues Myeloblastiques (GOELAM). Blood 1998 Apr 15; 91(8): 2722-2730.

10.Estey EH, Thall PF, Pierce S, Cortes J, Beran M, Kantarjian H, et al.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 1999 Apr 15; 93(8): 2478-2484.

11.Hast R, Hellstrom-Lindberg E, Ohm L, Bjorkholm M, Celsing F, Dahl IM, et al.No benefit from adding GM-CSF to induction chemotherapy in transforming myelodysplastic syndromes: better outcome in patients with less proliferative disease. Leukemia 2003 Sep; 17(9): 1827-1833.

12.Lowenberg B, van Putten W, Theobald M, Gmur J, Verdonck L, Sonneveld P, et al. Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. The New England journal of medicine 2003 Aug 21; 349(8): 743-752.

13.Buchner T, Berdel WE, Hiddemann W. Priming with granulocyte colony-stimulating factor--relation to high-dose cytarabine in acute myeloid leukemia. The New England journal of medicine 2004 May 20; 350(21): 2215-2216.

14.Bug G, Koschmieder S, Krauter J, Wiebe S, Hannig C, Hofmann W-K, et al.Priming with Granulocyte-Colony Stimulating Factor Did Not Improve Outcome in a Randomized Study of Elderly Acute Myeloid Leukemia but Increased Induction Mortality. ASH Annual Meeting Abstracts 2006 November 16, 2006; 108(11): 1980-.

15.Lofgren C, Paul C, Astrom M, Hast R, Hedenius M, Lerner R, et al.Granulocyte-macrophage colony-stimulating factor to increase efficacy of mitoxantrone, etoposide and cytarabine in previously untreated elderly patients with acute myeloid leukaemia: a Swedish multicentre randomized trial. British journal of haematology 2004 Feb; 124(4): 474-480.

16.Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, et al. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood 2004 Jan 15; 103(2): 479-485.

17.Amadori S, Suciu S, Jehn U, Stasi R, Thomas X, Marie JP, et al. 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 2005 Jul 1; 106(1): 27-34.

18.Milligan DW, Wheatley K, Littlewood T, Craig JI, Burnett AK. 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 2006 Jun 15; 107(12): 4614-4622.

19.Thomas X, Raffoux E, Botton S, Pautas C, Arnaud P, de Revel T, et al.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 2007 Mar; 21(3): 453-461.