title: Serum-tryptase at diagnosis: a novel biomarker improving prognostication in Ph(+) CML.
abstract: Basophilia is an established prognostic variable in Ph-chromosome+ chronic myeloid leukemia (CML). However, in CML, basophils are often immature and thus escape microscopic quantification. We have previously shown that tryptase is produced and secreted by immature CML basophils. In the current study, serum samples of 79 CML patients (chronic phase=CP, n=69; accelerated/blast phase=AP/BP, n=10) treated with BCR/ABL inhibitors, were analyzed for their tryptase content. Serum-tryptase levels at diagnosis were found to correlate with basophil counts and were higher in AP/BP patients (median tryptase: 29.9 ng/mL) compared to patients with CP (11.7 ng/mL; p<0.05). In 20/69 patients with CP, progression occurred. The progression-rate was higher in patients with tryptase >15 ng/mL (31%) compared to those with normal tryptase levels (9%, p<0.05). To validate tryptase as new prognostic variable, we replaced basophils by tryptase levels in the EUTOS score. This modified EUTOS-T score was found to predict progression-free and event-free survival significantly better, with p values of 0.000064 and 0.00369, respectively, compared to the original EUTOS score (progression-free survival: p=0.019; event-free survival: p=0.156). In conclusion, our data show that the serum-tryptase level at diagnosis is a powerful prognostic biomarker in CML. Inclusion of tryptase in prognostic CML scores may improve their predictive value.
authors: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna Vienna, Austria.
authors: Wolfgang R
authors: WR
authors: Sperr
authors: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna Vienna, Austria.
authors: Thomas
authors: T
authors: Pfeiffer
authors: Department of Laboratory Medicine, Medical University of Vienna Vienna, Austria.
authors: Gregor
authors: G
authors: Hoermann
authors: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna Vienna, Austria.
authors: Susanne
authors: S
authors: Herndlhofer
authors: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna Vienna, Austria.
authors: Christian
authors: C
authors: Sillaber
authors: Department of Laboratory Medicine, Medical University of Vienna Vienna, Austria.
authors: Christine
authors: C
authors: Mannhalter
authors: Institute of Environmental Health, Medical University of Vienna Vienna, Austria.
authors: Michael
authors: M
authors: Kundi
authors: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna Vienna, Austria ; Ludwig Boltzmann Cluster Oncology, Medical University of Vienna Vienna, Austria.
authors: Peter
authors: P
authors: Valent
keywords: CML; prognostication; scoring system; survival; tryptase
references: Leukemia. 2013 Jan;27(1):107-12
references: 22763385
references: Blood. 2001 Oct 1;98(7):2200-9
references: 11568008
references: N Engl J Med. 2003 Oct 9;349(15):1423-32
references: 14534335
references: J Clin Oncol. 2009 Dec 10;27(35):6041-51
references: 19884523
references: Cytogenet Cell Genet. 1981;31(1):5-23
references: 7297128
references: Blood. 1984 Apr;63(4):789-99
references: 6584184
references: Blood. 2012 May 10;119(19):4524-6
references: 22431574
references: Blood. 2002 Mar 1;99(5):1527-35
references: 11861264
references: Semin Hematol. 2003 Jan;40(1):79-86
references: 12563614
references: Eur J Clin Invest. 2009 Oct;39(10):914-23
references: 19522836
references: Wien Klin Wochenschr. 1998 Feb 13;110(3):79-88
references: 9553202
references: Haematologica. 2011 Oct;96(10):1395-7
references: 21972208
references: N Engl J Med. 2001 Apr 5;344(14):1031-7
references: 11287972
references: Am J Hematol. 2011 Jul;86(7):533-9
references: 21538470
references: Haematologica. 2010 Feb;95(2):224-31
references: 19833633
references: Int Arch Allergy Immunol. 2002 Jun;128(2):136-41
references: 12065914
references: Leukemia. 2003 Aug;17(8):1448-53
references: 12886230
references: Haematologica. 2008 Dec;93(12):1765-9
references: 19050065
references: Blood. 2008 Feb 15;111(4):1834-9
references: 18048643
references: Blood. 2011 Jul 21;118(3):686-92
references: 21536864
references: Blood. 2001 Oct 15;98(8):2580-3
references: 11588060
references: N Engl J Med. 2001 Apr 5;344(14):1038-42
references: 11287973
references: Blood. 2002 Mar 15;99(6):1928-37
references: 11877262
references: Blood. 2003 Jun 15;101(12 ):4660-6
references: 12676775
references: Haematologica. 2000 Dec;85(12):1248-54
references: 11114130
references: J Allergy Clin Immunol. 1990 Oct;86(4 Pt 2):594-8
references: 2229822
references: Blood. 2007 May 15;109(10):4143-50
references: 17264298
references: J Natl Cancer Inst. 1998 Jun 3;90(11):850-8
references: 9625174
references: Blood. 2006 Sep 15;108(6):1809-20
references: 16709930
references: N Engl J Med. 2010 Jun 17;362(24):2260-70
references: 20525995
references: Haematologica. 2011 Oct;96(10):1457-61
references: 21685471
references: N Engl J Med. 2006 Dec 7;355(23):2408-17
references: 17151364
references: N Engl J Med. 2003 Mar 13;348(11):994-1004
references: 12637609
references: Leukemia. 2009 Jun;23(6):1054-61
references: 19282833
references: Blood. 2008 Oct 15;112(8):3330-8
references: 18684859
references: Leuk Res. 2001 Jul;25(7):553-62
references: 11377680
references: J Clin Oncol. 2007 Sep 1;25(25):3908-14
references: 17761974