In:
Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4055-4055
Abstract:
Background In the recent International Prognostic Score for Thrombosis in essential thrombocythemia (IPSET-thrombosis), age and history of thrombosis were confirmed as independent risk factors for future thrombosis and the study also identified independent prothrombotic role for cardiovascular (CV) risk factors and JAK2 V617F mutation (Barbui et al. Blood 2012). Methods In the current study, we re-analyzed the original IPSET-thrombosis data in 1019 patients with WHO-defined ET in whom JAK2 mutational status was available, in order to quantify the individual contributions of JAK2 mutations and CV risk factors in conventionally-assigned low and high risk ET, as well as in age- versus thrombosis-defined high risk status. Results After a median follow-up of 6.8 and 5.0 years in conventionally-assigned low- and high-risk patients, respectively, the overall annual rate of total thrombosis (108 events) in conventionally-assigned low- and high-risk patients was 1.11%-pt/y (CI 0.81-1.52) and 2.46%-pt/y (CI 1.94-3.11) respectively (p=0.001), and the difference was mainly due to a higher frequency of arterial thrombosis in high-risk patients (p 〈 0.001).The influence of JAK2 mutational status and CV-risk factors on the rate of thrombosis in conventionally assigned low- and high-risk groups is presented in the table. Table 1. Additional risk factors N (%) Event Rate % pts/yr (95% CI) P-value P-value P-value trend Low risk 506 (50) 39 1.11 (0.81-1.52) None 200 (40) 7 0.44 (0.21-0.92) ref Cardiovascular risk factor 36 (7) 3 1.05 (0.34-3.25) 0.220 0.227 JAK2V617F 213 (43) 21 1.59 (1.04-2.44) 0.001 0.217 Both 52 (10) 8 2.57 (1.29-5.15) 〈 0.001 ref 〈 0.001 High risk 513 (50) 69 2.46 (1.94-3.11) None 111 (22) 10 1.44 (0.78-2.68) ref Cardiovascular risk factor 44 (9) 4 1.64 (0.62-4.37) 0.909 0.067 JAK2V617F 222 (43) 30 2.36 (1.65-3.38) 0.168 0.082 Both 136 (27) 25 4.17 (2.82-6.17) 0.011 ref 0.005 The number of major arterial and venous thrombosis was reported as rates per 100 patient-years and the difference among groups was assessed by Mantel Cox log-rank test i) Conventionally-assigned low-risk group. Amongst 506 patients, 200 (40%) displayed neither JAK2 mutation nor CV risk factors and their annual rate of thrombosis was 0.44%, as opposed to 1.05% in the presence of CV risk factors (P=NS), 1.59% in the presence of JAK2 mutation (p=0.001) and 2.57% in the presence of both CV risk factors and JAK2 mutation (P 〈 0.001). There was no significant difference when low-risk patients with both JAK2 mutation and CV risk factors were compared with either those with CV risk factors only (p=0.227) or those with JAK2 mutation only (p=0.217). ii) Conventionally assigned high-risk group: The absence or presence of one or both of the aforementioned additional risk factors for thrombosis were documented in 111 (22%), 44 (9%), 222 (43%) and 136 (27%) patients, respectively, with corresponding annual rates of thrombosis at 1.44%, 1.64%, 2.36% and 4.17% (Table). High-risk patients with both risk factors had a significantly higher risk of thrombosis compared to their counterparts with the absence of JAK2 mutations and CV risk factors (p=0.011). Additional analysis revealed limited enhancement of thrombosis risk by either JAK2 mutations or CV risk factors or both in patients whose high-risk status was defined by the presence of thrombosis history, regardless of age (P=NS). In contrast, the presence of JAK2 mutations, with or without CV risk factors, might have affected thrombosis risk in patients where high-risk status was defined by age alone (p=0.05). Conclusions The current study suggests the possibility of considering four risk categories in ET: "very low risk" group (age ≤60 years and without thrombosis history, JAK2 mutations or CV risk factors); "low risk" (age ≤60 years and without thrombosis history but with JAK2 mutations or CV risk factors); "intermediate risk" (age 〉 60 years but without thrombosis history or JAK2 mutations); and "high risk" (thrombosis history at any age or JAK2 -mutated patients who are older than 60 years of age). Treatment recommendations for each one of the above-mentioned new risk categories should be examined in the context of prospective controlled studies. Disclosures Barbui: Novartis: Speakers Bureau. Vannucchi:Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire: Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees. Buxhofer-Ausch:AOP Orphan: Research Funding. De Stefano:Novartis: Research Funding, Speakers Bureau; Janssen Cilag: Research Funding; Shire: Speakers Bureau; GlaxoSmithKline: Speakers Bureau; Bruno Farmaceutici: Research Funding; Roche: Research Funding; Amgen: Speakers Bureau; Celgene: Speakers Bureau. Gisslinger:Janssen Cilag: Honoraria, Speakers Bureau; AOP ORPHAN: Consultancy, Honoraria, Research Funding, Speakers Bureau; Geron: Consultancy; Sanofi Aventis: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V126.23.4055.4055
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2015
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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