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Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis

Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis
Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis
We evaluated the impact of clinical and molecular characteristics on overall survival (OS) in 108 patients with indolent (n=41) and advanced SM (advSM, n=67). Organomegaly was measured by magnetic resonance imaging (MRI)-based volumetry of liver and spleen. In multivariate analysis of all patients, an increased spleen volume greater than or equal to450?ml (hazard ratio [HR], 5.2; 95% confidence interval [CI], [2.1–13.0]; P=0.003) and an elevated alkaline phosphatase (AP; HR 5.0 [1.1–22.2]; P=0.02) were associated with adverse OS. The 3-year OS was 100, 77, and 39%, respectively (P<0.0001), for patients with 0 (low-risk, n=37), 1 (intermediate-risk, n=32) or 2 (high-risk, n=39) parameters. For advSM patients with fully available clinical and molecular data (n=60), univariate analysis identified splenomegaly greater than or equal to1200?ml, elevated AP and mutations in the SRSF2/ASXL1/RUNX1 (S/A/R) gene panel as significant prognostic markers. In multivariate analysis, mutations in S/A/R (HR, 3.2 [1.1–9.6]; P=0.01) and elevated AP (HR 2.6 [1.0–7.1]; P=0.03) remained predictive adverse prognostic markers for OS. The 3-year OS was 76% and 38%, respectively (P=0.0003), for patients with 0-1 (intermediate-risk, n=28) or 2 (high-risk, n=32) parameters. We conclude that splenomegaly, elevated AP and mutations in the S/A/R gene panel are independent of the WHO classification and provide the most relevant prognostic information in SM patients
0887-6924
2342-2350
Jawhar, M.
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Schwaab, J.
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Hausmann, D.
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Clemens, J.
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Naumann, N.
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Henzler, T.
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Horny, H.-P.
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Sotlar, K.
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Schoenberg, S.O.
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Cross, N.C.P.
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Fabarius, A.
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Hofmann, W.-K.
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Valent, P.
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Metzgeroth, G.
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Reiter, A.
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Jawhar, M.
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Schwaab, J.
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Hausmann, D.
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Clemens, J.
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Naumann, N.
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Henzler, T.
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Horny, H.-P.
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Sotlar, K.
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Schoenberg, S.O.
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Cross, N.C.P.
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Fabarius, A.
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Hofmann, W.-K.
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Valent, P.
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Metzgeroth, G.
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Reiter, A.
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Jawhar, M., Schwaab, J., Hausmann, D., Clemens, J., Naumann, N., Henzler, T., Horny, H.-P., Sotlar, K., Schoenberg, S.O., Cross, N.C.P., Fabarius, A., Hofmann, W.-K., Valent, P., Metzgeroth, G. and Reiter, A. (2016) Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis. Leukemia, 30 (12), 2342-2350. (doi:10.1038/leu.2016.190).

Record type: Article

Abstract

We evaluated the impact of clinical and molecular characteristics on overall survival (OS) in 108 patients with indolent (n=41) and advanced SM (advSM, n=67). Organomegaly was measured by magnetic resonance imaging (MRI)-based volumetry of liver and spleen. In multivariate analysis of all patients, an increased spleen volume greater than or equal to450?ml (hazard ratio [HR], 5.2; 95% confidence interval [CI], [2.1–13.0]; P=0.003) and an elevated alkaline phosphatase (AP; HR 5.0 [1.1–22.2]; P=0.02) were associated with adverse OS. The 3-year OS was 100, 77, and 39%, respectively (P<0.0001), for patients with 0 (low-risk, n=37), 1 (intermediate-risk, n=32) or 2 (high-risk, n=39) parameters. For advSM patients with fully available clinical and molecular data (n=60), univariate analysis identified splenomegaly greater than or equal to1200?ml, elevated AP and mutations in the SRSF2/ASXL1/RUNX1 (S/A/R) gene panel as significant prognostic markers. In multivariate analysis, mutations in S/A/R (HR, 3.2 [1.1–9.6]; P=0.01) and elevated AP (HR 2.6 [1.0–7.1]; P=0.03) remained predictive adverse prognostic markers for OS. The 3-year OS was 76% and 38%, respectively (P=0.0003), for patients with 0-1 (intermediate-risk, n=28) or 2 (high-risk, n=32) parameters. We conclude that splenomegaly, elevated AP and mutations in the S/A/R gene panel are independent of the WHO classification and provide the most relevant prognostic information in SM patients

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Accepted/In Press date: 10 June 2016
e-pub ahead of print date: 15 July 2016
Published date: December 2016
Organisations: Human Development & Health

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Local EPrints ID: 398591
URI: http://eprints.soton.ac.uk/id/eprint/398591
ISSN: 0887-6924
PURE UUID: b25325d1-e798-45bc-b062-9fbb304e7a00
ORCID for N.C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 29 Jul 2016 10:17
Last modified: 07 Oct 2020 05:47

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Contributors

Author: M. Jawhar
Author: J. Schwaab
Author: D. Hausmann
Author: J. Clemens
Author: N. Naumann
Author: T. Henzler
Author: H.-P. Horny
Author: K. Sotlar
Author: S.O. Schoenberg
Author: N.C.P. Cross ORCID iD
Author: A. Fabarius
Author: W.-K. Hofmann
Author: P. Valent
Author: G. Metzgeroth
Author: A. Reiter

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