Mutations and thrombosis in essential thrombocythemia: Prognostic interaction with age and thrombosis history

Naseema Gangat, Emnet A. Wassie, Terra L. Lasho, Christy Finke, Rhett P. Ketterling, Curtis A. Hanson, Animesh D Pardanani, Alexandra P. Wolanskyj, Margherita Maffioli, Rosario Casalone, Francesco Passamonti, Ayalew Tefferi

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: Vascular events in essential thrombocythemia (ET) are associated with advanced age and thrombosis history. Recent information suggests additional effect from the presence of specific mutations. Objectives: To examine the influence of age and thrombosis history on the reported association between mutational status and thrombosis-free survival in ET. Patients and Methods: Analysis was performed using a Mayo Clinic cohort of 300 ET patients, and key findings were reanalyzed by including additional 102 Italian patients. Results: Among 300 Mayo patients with ET (median age 55 yr, 60% females), mutational frequencies were 53% JAK2, 32% CALR, 3% MPL, and 12% JAK2, CALR and MPL wild type. One hundred and six (35%) patients experienced arterial (n = 75) or venous (n = 43) events, before (n = 55) or after (n = 71) diagnosis. In univariate analysis, compared to JAK2-mutated cases, JAK2, CALR and MPL wild type (HR 0.31, 95% CI 0.11-0.86), and CALR-mutated (0.53, 95% CI 0.30-0.92) patients displayed better thrombosis-free survival. JAK2, CALR, and MPL wild type remained significant (P = 0.03; HR 0.32, 95% CI 0.11-0.9) during multivariable analysis that included age (P = 0.01) and thrombosis history (P = 0.0006); a favorable impact from CALR mutations was of borderline significance (P = 0.1; HR 0.62, 95% CI 0.35-1.1), but became significant (P = 0.02) when multivariable analysis including thrombosis history (P = 0.02) was performed on patients younger than 60 yr of age. Conclusions: The favorable impact of mutational status on thrombosis-free survival in ET might be most evident for JAK2, CALR, and MPL wild type patients, whereas the favorable effect from CALR mutations might be confined to young patients.

Original languageEnglish (US)
Pages (from-to)31-36
Number of pages6
JournalEuropean Journal of Haematology
Volume94
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Essential Thrombocythemia
Thrombosis
Mutation
Survival
Blood Vessels

Keywords

  • Calreticulin
  • Essential thrombocythemia
  • Janus kinase 2
  • Mutation
  • Thrombosis

ASJC Scopus subject areas

  • Hematology

Cite this

Mutations and thrombosis in essential thrombocythemia : Prognostic interaction with age and thrombosis history. / Gangat, Naseema; Wassie, Emnet A.; Lasho, Terra L.; Finke, Christy; Ketterling, Rhett P.; Hanson, Curtis A.; Pardanani, Animesh D; Wolanskyj, Alexandra P.; Maffioli, Margherita; Casalone, Rosario; Passamonti, Francesco; Tefferi, Ayalew.

In: European Journal of Haematology, Vol. 94, No. 1, 01.01.2015, p. 31-36.

Research output: Contribution to journalArticle

Gangat, N, Wassie, EA, Lasho, TL, Finke, C, Ketterling, RP, Hanson, CA, Pardanani, AD, Wolanskyj, AP, Maffioli, M, Casalone, R, Passamonti, F & Tefferi, A 2015, 'Mutations and thrombosis in essential thrombocythemia: Prognostic interaction with age and thrombosis history', European Journal of Haematology, vol. 94, no. 1, pp. 31-36. https://doi.org/10.1111/ejh.12389
Gangat, Naseema ; Wassie, Emnet A. ; Lasho, Terra L. ; Finke, Christy ; Ketterling, Rhett P. ; Hanson, Curtis A. ; Pardanani, Animesh D ; Wolanskyj, Alexandra P. ; Maffioli, Margherita ; Casalone, Rosario ; Passamonti, Francesco ; Tefferi, Ayalew. / Mutations and thrombosis in essential thrombocythemia : Prognostic interaction with age and thrombosis history. In: European Journal of Haematology. 2015 ; Vol. 94, No. 1. pp. 31-36.
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abstract = "Background: Vascular events in essential thrombocythemia (ET) are associated with advanced age and thrombosis history. Recent information suggests additional effect from the presence of specific mutations. Objectives: To examine the influence of age and thrombosis history on the reported association between mutational status and thrombosis-free survival in ET. Patients and Methods: Analysis was performed using a Mayo Clinic cohort of 300 ET patients, and key findings were reanalyzed by including additional 102 Italian patients. Results: Among 300 Mayo patients with ET (median age 55 yr, 60{\%} females), mutational frequencies were 53{\%} JAK2, 32{\%} CALR, 3{\%} MPL, and 12{\%} JAK2, CALR and MPL wild type. One hundred and six (35{\%}) patients experienced arterial (n = 75) or venous (n = 43) events, before (n = 55) or after (n = 71) diagnosis. In univariate analysis, compared to JAK2-mutated cases, JAK2, CALR and MPL wild type (HR 0.31, 95{\%} CI 0.11-0.86), and CALR-mutated (0.53, 95{\%} CI 0.30-0.92) patients displayed better thrombosis-free survival. JAK2, CALR, and MPL wild type remained significant (P = 0.03; HR 0.32, 95{\%} CI 0.11-0.9) during multivariable analysis that included age (P = 0.01) and thrombosis history (P = 0.0006); a favorable impact from CALR mutations was of borderline significance (P = 0.1; HR 0.62, 95{\%} CI 0.35-1.1), but became significant (P = 0.02) when multivariable analysis including thrombosis history (P = 0.02) was performed on patients younger than 60 yr of age. Conclusions: The favorable impact of mutational status on thrombosis-free survival in ET might be most evident for JAK2, CALR, and MPL wild type patients, whereas the favorable effect from CALR mutations might be confined to young patients.",
keywords = "Calreticulin, Essential thrombocythemia, Janus kinase 2, Mutation, Thrombosis",
author = "Naseema Gangat and Wassie, {Emnet A.} and Lasho, {Terra L.} and Christy Finke and Ketterling, {Rhett P.} and Hanson, {Curtis A.} and Pardanani, {Animesh D} and Wolanskyj, {Alexandra P.} and Margherita Maffioli and Rosario Casalone and Francesco Passamonti and Ayalew Tefferi",
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T1 - Mutations and thrombosis in essential thrombocythemia

T2 - Prognostic interaction with age and thrombosis history

AU - Gangat, Naseema

AU - Wassie, Emnet A.

AU - Lasho, Terra L.

AU - Finke, Christy

AU - Ketterling, Rhett P.

AU - Hanson, Curtis A.

AU - Pardanani, Animesh D

AU - Wolanskyj, Alexandra P.

AU - Maffioli, Margherita

AU - Casalone, Rosario

AU - Passamonti, Francesco

AU - Tefferi, Ayalew

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background: Vascular events in essential thrombocythemia (ET) are associated with advanced age and thrombosis history. Recent information suggests additional effect from the presence of specific mutations. Objectives: To examine the influence of age and thrombosis history on the reported association between mutational status and thrombosis-free survival in ET. Patients and Methods: Analysis was performed using a Mayo Clinic cohort of 300 ET patients, and key findings were reanalyzed by including additional 102 Italian patients. Results: Among 300 Mayo patients with ET (median age 55 yr, 60% females), mutational frequencies were 53% JAK2, 32% CALR, 3% MPL, and 12% JAK2, CALR and MPL wild type. One hundred and six (35%) patients experienced arterial (n = 75) or venous (n = 43) events, before (n = 55) or after (n = 71) diagnosis. In univariate analysis, compared to JAK2-mutated cases, JAK2, CALR and MPL wild type (HR 0.31, 95% CI 0.11-0.86), and CALR-mutated (0.53, 95% CI 0.30-0.92) patients displayed better thrombosis-free survival. JAK2, CALR, and MPL wild type remained significant (P = 0.03; HR 0.32, 95% CI 0.11-0.9) during multivariable analysis that included age (P = 0.01) and thrombosis history (P = 0.0006); a favorable impact from CALR mutations was of borderline significance (P = 0.1; HR 0.62, 95% CI 0.35-1.1), but became significant (P = 0.02) when multivariable analysis including thrombosis history (P = 0.02) was performed on patients younger than 60 yr of age. Conclusions: The favorable impact of mutational status on thrombosis-free survival in ET might be most evident for JAK2, CALR, and MPL wild type patients, whereas the favorable effect from CALR mutations might be confined to young patients.

AB - Background: Vascular events in essential thrombocythemia (ET) are associated with advanced age and thrombosis history. Recent information suggests additional effect from the presence of specific mutations. Objectives: To examine the influence of age and thrombosis history on the reported association between mutational status and thrombosis-free survival in ET. Patients and Methods: Analysis was performed using a Mayo Clinic cohort of 300 ET patients, and key findings were reanalyzed by including additional 102 Italian patients. Results: Among 300 Mayo patients with ET (median age 55 yr, 60% females), mutational frequencies were 53% JAK2, 32% CALR, 3% MPL, and 12% JAK2, CALR and MPL wild type. One hundred and six (35%) patients experienced arterial (n = 75) or venous (n = 43) events, before (n = 55) or after (n = 71) diagnosis. In univariate analysis, compared to JAK2-mutated cases, JAK2, CALR and MPL wild type (HR 0.31, 95% CI 0.11-0.86), and CALR-mutated (0.53, 95% CI 0.30-0.92) patients displayed better thrombosis-free survival. JAK2, CALR, and MPL wild type remained significant (P = 0.03; HR 0.32, 95% CI 0.11-0.9) during multivariable analysis that included age (P = 0.01) and thrombosis history (P = 0.0006); a favorable impact from CALR mutations was of borderline significance (P = 0.1; HR 0.62, 95% CI 0.35-1.1), but became significant (P = 0.02) when multivariable analysis including thrombosis history (P = 0.02) was performed on patients younger than 60 yr of age. Conclusions: The favorable impact of mutational status on thrombosis-free survival in ET might be most evident for JAK2, CALR, and MPL wild type patients, whereas the favorable effect from CALR mutations might be confined to young patients.

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KW - Janus kinase 2

KW - Mutation

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