CLINICAL FEATURES OF DIFFERENT GENOTYPES IN A COHORT OF 172 PATIENTS WITH CALRETICULIN-MUTATED ESSENTIAL THROMBOCYTHEMIA
(Abstract release date: 05/19/16)
EHA Library. De Stefano V. 06/09/16; 132900; E1351
Prof. Valerio De Stefano
Contributions
Contributions
Abstract
Abstract: E1351
Type: Eposter Presentation
Background
Calreticulin (CALR) mutations occur in 15-24% of patients with essential thrombocythemia. The 52-bp deletion (mutation type 1) and the 5-bp insertion (mutation type 2) are the most frequent alterations, being 45-53% and 32-39% of all mutations; the remaining types are described in very few patients each. CARL-mutated ET has a higher platelet count, a lower leukocyte count, a lower haemoglobin level, and a lower thrombotic risk in respect to the JAK2 V617F-ET. However, the differences between types 1 and 2 have been rarely investigated (Tefferi A et al, Am J Hematol 2014; 89: E121).
Aims
To assess in a retrospective multicenter cohort of CALR-mutated ET patients the clinical and laboratory features of type 1, type 2, and types non-1/non-2.
Methods
We analysed a retrospective cohort of 172 patients with CALR-mutated ET diagnosed according to the updated WHO 2014 criteria. CALR mutation was type 1 in 91 patients (52.9%) (M/F 46/45, median age at diagnosis 59 yrs, range 18-84), type 2 in 55 patients (32.0%) (M/F 17/38, median age at diagnosis 43 yrs, range 17-85), and type non-1/non-2 in 26 patients (15.1%) (M/F 11/15, median age at diagnosis 46 yrs, range 20-83). Laboratory and clinical features were compared among the groups. The relative risk of thrombosis between groups was estimated by a Cox proportional hazards model.
Results
The total observation time was 1586 pt-years (median 7.5, range 0.1-34 years). As previously reported, male sex and younger age were more present in type 1 mutation than in type 2 (p=0.02 and p=0.002, respectively). On the other hand, no significant difference in sex and age distribution was found between patients with type non-1/non-2 mutation and those with type 1 and type 2. Patients with type 1, type 2, and type non-1/non-2 mutations did not significantly differ in the rate of splenomegaly (10.9% vs.14.5% vs. 0%), Hb gr/dL (median 13.4, range 9.4-16.5 vs. median 13.6, range 11-16 vs. median 13.6, range 10.9-13.4), Hct (median 0.40, range 0.28-0.49 vs. median 0.41, range 0.33-0.43 vs. median 0.40, range 0.32-0.48), leukocyte count x109/L (median 8.43, range 4.63-17.15 vs. median 8.05, range 3.56-13.40 vs. median 7.82, range 4.55-15.30), and platelet count x109/L (median 787, range 454-2000 vs. median 920, range 465-1743 vs. median 887, range 453-2042). As for clinical phenotype, patients with type 1, type 2, and type non-1/non-2 mutations did not significantly differ in the rate of microvascular disturbances (17.5% vs. 16.3% vs. 15.3%), need of cytoreduction (71.4% vs. 72.7% vs. 73.0%), major bleeding (19.7% vs. 27.2% vs. 23.0%), transformation to myelofibrosis (9.8% vs. 12.7% vs. 11.5%), occurrence of solid neoplasia (14.2% vs. 9.0% vs. 7.6%). No patient evolved to acute leukemia. Thrombosis occurred in type 1 in 26.3% of cases (arterial thrombosis in 14 cases, venous in 8, both sites in 2), in type 2 in 21.8% of cases (arterial thrombosis in 6 cases, venous in 6), and in type non-1/non-2 in 7.6% of cases (arterial thrombosis in 2 cases). In patients with type 1 the risk of thrombosis was increased over time with a borderline statistical significance in comparison with type 2 (hazard ratio, HR, 1.77, 95%CI 0.91-3.64) and type non-1/non-2 (HR 3.31, 95%CI 0.91-6.29).
Conclusion
Male sex and younger age are confirmed to be more present in type 1 than in type 2. In this cohort of ET patients the type of CALR mutation did not influence significantly other laboratory and clinical features. However, a trend towards a higher thrombotic risk was displayed in type 1, deserving further studies.
Session topic: E-poster
Keyword(s): Essential Thrombocytemia, Myeloproliferative disorder, Thrombosis
Type: Eposter Presentation
Background
Calreticulin (CALR) mutations occur in 15-24% of patients with essential thrombocythemia. The 52-bp deletion (mutation type 1) and the 5-bp insertion (mutation type 2) are the most frequent alterations, being 45-53% and 32-39% of all mutations; the remaining types are described in very few patients each. CARL-mutated ET has a higher platelet count, a lower leukocyte count, a lower haemoglobin level, and a lower thrombotic risk in respect to the JAK2 V617F-ET. However, the differences between types 1 and 2 have been rarely investigated (Tefferi A et al, Am J Hematol 2014; 89: E121).
Aims
To assess in a retrospective multicenter cohort of CALR-mutated ET patients the clinical and laboratory features of type 1, type 2, and types non-1/non-2.
Methods
We analysed a retrospective cohort of 172 patients with CALR-mutated ET diagnosed according to the updated WHO 2014 criteria. CALR mutation was type 1 in 91 patients (52.9%) (M/F 46/45, median age at diagnosis 59 yrs, range 18-84), type 2 in 55 patients (32.0%) (M/F 17/38, median age at diagnosis 43 yrs, range 17-85), and type non-1/non-2 in 26 patients (15.1%) (M/F 11/15, median age at diagnosis 46 yrs, range 20-83). Laboratory and clinical features were compared among the groups. The relative risk of thrombosis between groups was estimated by a Cox proportional hazards model.
Results
The total observation time was 1586 pt-years (median 7.5, range 0.1-34 years). As previously reported, male sex and younger age were more present in type 1 mutation than in type 2 (p=0.02 and p=0.002, respectively). On the other hand, no significant difference in sex and age distribution was found between patients with type non-1/non-2 mutation and those with type 1 and type 2. Patients with type 1, type 2, and type non-1/non-2 mutations did not significantly differ in the rate of splenomegaly (10.9% vs.14.5% vs. 0%), Hb gr/dL (median 13.4, range 9.4-16.5 vs. median 13.6, range 11-16 vs. median 13.6, range 10.9-13.4), Hct (median 0.40, range 0.28-0.49 vs. median 0.41, range 0.33-0.43 vs. median 0.40, range 0.32-0.48), leukocyte count x109/L (median 8.43, range 4.63-17.15 vs. median 8.05, range 3.56-13.40 vs. median 7.82, range 4.55-15.30), and platelet count x109/L (median 787, range 454-2000 vs. median 920, range 465-1743 vs. median 887, range 453-2042). As for clinical phenotype, patients with type 1, type 2, and type non-1/non-2 mutations did not significantly differ in the rate of microvascular disturbances (17.5% vs. 16.3% vs. 15.3%), need of cytoreduction (71.4% vs. 72.7% vs. 73.0%), major bleeding (19.7% vs. 27.2% vs. 23.0%), transformation to myelofibrosis (9.8% vs. 12.7% vs. 11.5%), occurrence of solid neoplasia (14.2% vs. 9.0% vs. 7.6%). No patient evolved to acute leukemia. Thrombosis occurred in type 1 in 26.3% of cases (arterial thrombosis in 14 cases, venous in 8, both sites in 2), in type 2 in 21.8% of cases (arterial thrombosis in 6 cases, venous in 6), and in type non-1/non-2 in 7.6% of cases (arterial thrombosis in 2 cases). In patients with type 1 the risk of thrombosis was increased over time with a borderline statistical significance in comparison with type 2 (hazard ratio, HR, 1.77, 95%CI 0.91-3.64) and type non-1/non-2 (HR 3.31, 95%CI 0.91-6.29).
Conclusion
Male sex and younger age are confirmed to be more present in type 1 than in type 2. In this cohort of ET patients the type of CALR mutation did not influence significantly other laboratory and clinical features. However, a trend towards a higher thrombotic risk was displayed in type 1, deserving further studies.
Session topic: E-poster
Keyword(s): Essential Thrombocytemia, Myeloproliferative disorder, Thrombosis
Abstract: E1351
Type: Eposter Presentation
Background
Calreticulin (CALR) mutations occur in 15-24% of patients with essential thrombocythemia. The 52-bp deletion (mutation type 1) and the 5-bp insertion (mutation type 2) are the most frequent alterations, being 45-53% and 32-39% of all mutations; the remaining types are described in very few patients each. CARL-mutated ET has a higher platelet count, a lower leukocyte count, a lower haemoglobin level, and a lower thrombotic risk in respect to the JAK2 V617F-ET. However, the differences between types 1 and 2 have been rarely investigated (Tefferi A et al, Am J Hematol 2014; 89: E121).
Aims
To assess in a retrospective multicenter cohort of CALR-mutated ET patients the clinical and laboratory features of type 1, type 2, and types non-1/non-2.
Methods
We analysed a retrospective cohort of 172 patients with CALR-mutated ET diagnosed according to the updated WHO 2014 criteria. CALR mutation was type 1 in 91 patients (52.9%) (M/F 46/45, median age at diagnosis 59 yrs, range 18-84), type 2 in 55 patients (32.0%) (M/F 17/38, median age at diagnosis 43 yrs, range 17-85), and type non-1/non-2 in 26 patients (15.1%) (M/F 11/15, median age at diagnosis 46 yrs, range 20-83). Laboratory and clinical features were compared among the groups. The relative risk of thrombosis between groups was estimated by a Cox proportional hazards model.
Results
The total observation time was 1586 pt-years (median 7.5, range 0.1-34 years). As previously reported, male sex and younger age were more present in type 1 mutation than in type 2 (p=0.02 and p=0.002, respectively). On the other hand, no significant difference in sex and age distribution was found between patients with type non-1/non-2 mutation and those with type 1 and type 2. Patients with type 1, type 2, and type non-1/non-2 mutations did not significantly differ in the rate of splenomegaly (10.9% vs.14.5% vs. 0%), Hb gr/dL (median 13.4, range 9.4-16.5 vs. median 13.6, range 11-16 vs. median 13.6, range 10.9-13.4), Hct (median 0.40, range 0.28-0.49 vs. median 0.41, range 0.33-0.43 vs. median 0.40, range 0.32-0.48), leukocyte count x109/L (median 8.43, range 4.63-17.15 vs. median 8.05, range 3.56-13.40 vs. median 7.82, range 4.55-15.30), and platelet count x109/L (median 787, range 454-2000 vs. median 920, range 465-1743 vs. median 887, range 453-2042). As for clinical phenotype, patients with type 1, type 2, and type non-1/non-2 mutations did not significantly differ in the rate of microvascular disturbances (17.5% vs. 16.3% vs. 15.3%), need of cytoreduction (71.4% vs. 72.7% vs. 73.0%), major bleeding (19.7% vs. 27.2% vs. 23.0%), transformation to myelofibrosis (9.8% vs. 12.7% vs. 11.5%), occurrence of solid neoplasia (14.2% vs. 9.0% vs. 7.6%). No patient evolved to acute leukemia. Thrombosis occurred in type 1 in 26.3% of cases (arterial thrombosis in 14 cases, venous in 8, both sites in 2), in type 2 in 21.8% of cases (arterial thrombosis in 6 cases, venous in 6), and in type non-1/non-2 in 7.6% of cases (arterial thrombosis in 2 cases). In patients with type 1 the risk of thrombosis was increased over time with a borderline statistical significance in comparison with type 2 (hazard ratio, HR, 1.77, 95%CI 0.91-3.64) and type non-1/non-2 (HR 3.31, 95%CI 0.91-6.29).
Conclusion
Male sex and younger age are confirmed to be more present in type 1 than in type 2. In this cohort of ET patients the type of CALR mutation did not influence significantly other laboratory and clinical features. However, a trend towards a higher thrombotic risk was displayed in type 1, deserving further studies.
Session topic: E-poster
Keyword(s): Essential Thrombocytemia, Myeloproliferative disorder, Thrombosis
Type: Eposter Presentation
Background
Calreticulin (CALR) mutations occur in 15-24% of patients with essential thrombocythemia. The 52-bp deletion (mutation type 1) and the 5-bp insertion (mutation type 2) are the most frequent alterations, being 45-53% and 32-39% of all mutations; the remaining types are described in very few patients each. CARL-mutated ET has a higher platelet count, a lower leukocyte count, a lower haemoglobin level, and a lower thrombotic risk in respect to the JAK2 V617F-ET. However, the differences between types 1 and 2 have been rarely investigated (Tefferi A et al, Am J Hematol 2014; 89: E121).
Aims
To assess in a retrospective multicenter cohort of CALR-mutated ET patients the clinical and laboratory features of type 1, type 2, and types non-1/non-2.
Methods
We analysed a retrospective cohort of 172 patients with CALR-mutated ET diagnosed according to the updated WHO 2014 criteria. CALR mutation was type 1 in 91 patients (52.9%) (M/F 46/45, median age at diagnosis 59 yrs, range 18-84), type 2 in 55 patients (32.0%) (M/F 17/38, median age at diagnosis 43 yrs, range 17-85), and type non-1/non-2 in 26 patients (15.1%) (M/F 11/15, median age at diagnosis 46 yrs, range 20-83). Laboratory and clinical features were compared among the groups. The relative risk of thrombosis between groups was estimated by a Cox proportional hazards model.
Results
The total observation time was 1586 pt-years (median 7.5, range 0.1-34 years). As previously reported, male sex and younger age were more present in type 1 mutation than in type 2 (p=0.02 and p=0.002, respectively). On the other hand, no significant difference in sex and age distribution was found between patients with type non-1/non-2 mutation and those with type 1 and type 2. Patients with type 1, type 2, and type non-1/non-2 mutations did not significantly differ in the rate of splenomegaly (10.9% vs.14.5% vs. 0%), Hb gr/dL (median 13.4, range 9.4-16.5 vs. median 13.6, range 11-16 vs. median 13.6, range 10.9-13.4), Hct (median 0.40, range 0.28-0.49 vs. median 0.41, range 0.33-0.43 vs. median 0.40, range 0.32-0.48), leukocyte count x109/L (median 8.43, range 4.63-17.15 vs. median 8.05, range 3.56-13.40 vs. median 7.82, range 4.55-15.30), and platelet count x109/L (median 787, range 454-2000 vs. median 920, range 465-1743 vs. median 887, range 453-2042). As for clinical phenotype, patients with type 1, type 2, and type non-1/non-2 mutations did not significantly differ in the rate of microvascular disturbances (17.5% vs. 16.3% vs. 15.3%), need of cytoreduction (71.4% vs. 72.7% vs. 73.0%), major bleeding (19.7% vs. 27.2% vs. 23.0%), transformation to myelofibrosis (9.8% vs. 12.7% vs. 11.5%), occurrence of solid neoplasia (14.2% vs. 9.0% vs. 7.6%). No patient evolved to acute leukemia. Thrombosis occurred in type 1 in 26.3% of cases (arterial thrombosis in 14 cases, venous in 8, both sites in 2), in type 2 in 21.8% of cases (arterial thrombosis in 6 cases, venous in 6), and in type non-1/non-2 in 7.6% of cases (arterial thrombosis in 2 cases). In patients with type 1 the risk of thrombosis was increased over time with a borderline statistical significance in comparison with type 2 (hazard ratio, HR, 1.77, 95%CI 0.91-3.64) and type non-1/non-2 (HR 3.31, 95%CI 0.91-6.29).
Conclusion
Male sex and younger age are confirmed to be more present in type 1 than in type 2. In this cohort of ET patients the type of CALR mutation did not influence significantly other laboratory and clinical features. However, a trend towards a higher thrombotic risk was displayed in type 1, deserving further studies.
Session topic: E-poster
Keyword(s): Essential Thrombocytemia, Myeloproliferative disorder, Thrombosis
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