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 language | English (US) |
|---|---|
| Pages (from-to) | 31-36 |
| Number of pages | 6 |
| Journal | European Journal of Haematology |
| Volume | 94 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2015 |
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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 journal › Article
}
TY - JOUR
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.
KW - Calreticulin
KW - Essential thrombocythemia
KW - Janus kinase 2
KW - Mutation
KW - Thrombosis
UR - http://www.scopus.com/inward/record.url?scp=84922935914&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922935914&partnerID=8YFLogxK
U2 - 10.1111/ejh.12389
DO - 10.1111/ejh.12389
M3 - Article
C2 - 24889737
AN - SCOPUS:84922935914
VL - 94
SP - 31
EP - 36
JO - European Journal of Haematology
JF - European Journal of Haematology
SN - 0902-4441
IS - 1
ER -