title: Prognostic impact of white blood cell count in intermediate risk acute myeloid leukemia: relevance of mutated NPM1 and FLT3-ITD.
abstract: BACKGROUND
  High white blood cell count at presentation is an unfavorable prognostic factor for treatment outcome in intermediate cytogenetic risk acute myeloid leukemia. Since the impact of white blood cell count on outcome of subgroups defined by the molecular markers NPMc(+) and FLT3-internal tandem duplication (ITD) is unknown, we addressed this issue.
  
  
  METHODS
  We studied the effect of white blood cell count on outcome in a clinically and molecularly well-defined cohort of 525 patients with acute myeloid leukemia using these molecular markers. In addition, since an increased white blood cell count has been associated with an increased FLT3-ITD/FLT3 (wild-type) ratio, we investigated whether the effect of white blood cell count on outcome could be explained by the FLT3-ITD/FLT3 ratio.
  
  
  RESULTS
  This analysis revealed that white blood cell count had no impact on outcome in patients with the genotypic combinations 'NPMc(+) without FLT3-ITD' and 'NPM1 wild-type with or without FLT3-ITD'. In contrast, white blood cell count had a significant impact on complete remission rate (P=0.034), event-free survival (P=0.009) and overall survival (P<0.001) in patients with the genotypic combination 'NPMc(+) with FLT3-ITD'. A FLT3-ITD/FLT3 ratio greater than 1 was also associated with a reduced complete remission rate (P=0.066) and significantly reduced event-free survival (P= 0.001) and overall survival (P=0.001) in patients with the genotypic combination 'NPMc(+) with FLT3-ITD'. Multivariable analysis revealed that white blood cell count and FLT3-ITD/FLT3 ratio were independent prognostic indicators for outcome in the subgroup with the genotypic combination 'NPMc(+) with FLT3-ITD'.
  
  
  CONCLUSIONS
  Our results demonstrate that both high white blood cell count and FLT3-ITD/FLT3 ratio are prognostic factors in patients with acute myeloid leukemia with the genotypic combination 'NPMc(+) with FLT3-ITD'.
authors: Division of Pediatric Oncology/Hematology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, the Netherlands.
authors: Hendrik J M
authors: HJ
authors: de Jonge
authors: Peter J M
authors: PJ
authors: Valk
authors: Eveline S J M
authors: ES
authors: de Bont
authors: Jan Jacob
authors: JJ
authors: Schuringa
authors: Gert
authors: G
authors: Ossenkoppele
authors: Edo
authors: E
authors: Vellenga
authors: Gerwin
authors: G
authors: Huls
references: Blood. 1999 Jun 15;93(12):4131-43
references: 10361110
references: Blood. 2005 Dec 1;106(12):3733-9
references: 16076867
references: Blood. 1999 May 1;93(9):3074-80
references: 10216104
references: Leukemia. 1989 Apr;3(4):257-63
references: 2927176
references: Cancer. 1983 Sep 1;52(5):773-9
references: 6575857
references: Blood. 2002 Dec 15;100(13):4325-36
references: 12393746
references: N Engl J Med. 2008 May 1;358(18):1909-18
references: 18450602
references: Blood. 2009 Apr 23;113(17):4074-7
references: 18483393
references: Blood. 2006 May 15;107(10):4011-20
references: 16455956
references: J Clin Oncol. 2008 Oct 10;26(29):4791-7
references: 18695255
references: N Engl J Med. 2005 Jan 20;352(3):254-66
references: 15659725
references: Blood. 2005 Dec 1;106(12):3747-54
references: 16109776
references: J Clin Oncol. 1997 Dec;15(12):3496-506
references: 9396403
references: Blood. 2000 Dec 15;96(13):4075-83
references: 11110676
references: Blood. 2009 May 21;113(21):5250-3
references: 19279329
references: Blood. 2002 Jun 15;99(12):4326-35
references: 12036858
references: N Engl J Med. 1999 Sep 30;341(14):1051-62
references: 10502596
references: Blood. 2007 Feb 1;109(3):874-85
references: 17008539
references: Blood. 2002 May 15;99(10):3517-23
references: 11986202
references: N Engl J Med. 2003 Aug 21;349(8):743-52
references: 12930926
references: Lancet. 1986 Nov 29;2(8518):1236-41
references: 2878130
references: N Engl J Med. 2009 Sep 24;361(13):1235-48
references: 19776405
references: Leukemia. 2008 Jun;22(6):1234-40
references: 18401421
references: Blood. 2010 Jan 21;115(3):453-74
references: 19880497
references: Blood. 2001 Sep 15;98(6):1752-9
references: 11535508
references: Leukemia. 1996 Dec;10(12):1911-8
references: 8946930
references: Lancet. 2006 Nov 25;368(9550):1894-907
references: 17126723
references: J Clin Oncol. 1987 Sep;5(9):1364-72
references: 3625254
references: Br J Haematol. 1999 Oct;107(1):69-79
references: 10520026
references: Leukemia. 2006 Dec;20(12):2130-6
references: 17066094
references: Blood. 2002 Dec 15;100(13):4372-80
references: 12393388
references: Cancer Res. 2001 Oct 1;61(19):7233-9
references: 11585760
references: Blood. 2008 Mar 1;111(5):2776-84
references: 17957027
references: Blood. 1998 Oct 1;92(7):2322-33
references: 9746770
references: Blood. 2004 Apr 15;103(8):2908-13
references: 15070662
references: Blood. 2009 Sep 17;114(12):2386-92
references: 19602710