Manuel M Pérez Encinas1, Marta Sobas2, María Teresa Gómez-Casares3, Aitor Abuin Blanco1, María Soledad Noya Pereira4, José María Raya5, Marcio M Andrade-Campos6, Alberto Álvarez Larrán7, Krzysztof Lewandowski8, Szukalski Łukasz9, Juan Carlos Hernández Boluda10, Francisca Ferrer-Marín11, María Laura Fox12, Aleksandra Gołos13, Mercedes Gasior Kabat14, Elena Magro Mazo15, Anna Czyż2, Alejandro Martín Martín5, Beatriz Bellosillo Paricio6, Celsa Quinteiro García16, Jesús María González Martín17, Ruth Stuckey3. 1. Hematology Department, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Galicia, Spain. 2. Department of Hematology and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland. 3. Hematology Department, Hospital Universitario de Gran Canaria Dr.Negrín, Las Palmas de Gran Canaria, Spain. 4. Hematology Department, Hospital Clínico Universitario de A Coruña, A Coruña, Spain. 5. Hematology Department, Hospital, Universitario de Canarias, Santa Cruz de Tenerife, Spain. 6. Hematology Department, Hospital del Mar-IMIM, Barcelona, Spain. 7. Hematology Department, Hospital Clínic, Barcelona, Spain. 8. Department of Hematology and Bone Marrow Transplantation, University of Medical Sciences, Poznan, Poland. 9. Department of Hematology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Torun, Poland. 10. Hematology Department, Hospital Clínico, Valencia, Spain. 11. Hematology Department, Hospital Morales Meseguer, IMIB, UCAM, Murcia, Spain. 12. Hematology Department, Hospital Vall d'Hebron, Barcelona, Spain. 13. Department of Clinical Oncology and Chemotherapy, Magodent Hospital, Warsaw, Poland. 14. Hematology Department, Madrid, Spain. 15. Hematology Department, Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain. 16. Genomics Laboratory, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain. 17. Investigation Unit, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain.
Abstract
OBJECTIVES: In patients with essential thrombocythemia (ET), after the JAK2V617F driver mutation, mutations in CALR are common (classified as type 1, 52-bp deletion or type 2, 5-bp insertion). CALR mutations have generally been associated with a lower risk of thrombosis. This study aimed to confirm the impact of CALR mutation type on thrombotic risk. METHODS: We retrospectively investigated 983 ET patients diagnosed in Spanish and Polish hospitals. RESULTS: With 7.5 years of median follow-up from diagnosis, 155 patients (15.8%) had one or more thrombotic event. The 5-year thrombosis-free survival (TFS) rate was 83.8%, 91.6% and 93.9% for the JAK2V617F, CALR-type 1 and CALR-type 2 groups, respectively (P = .002). Comparing CALR-type 1 and CALR-type 2 groups, TFS for venous thrombosis was lower in CALR-type 1 (P = .046), with no difference in TFS for arterial thrombosis observed. The cumulative incidence of thrombosis was significantly different comparing JAK2V617F vs CALR-type 2 groups but not JAK2V617F vs CALR-type 1 groups. Moreover, CALR-type 2 mutation was a statistically significant protective factor for thrombosis with respect to JAK2V617F in multivariate logistic regression (OR: 0.45, P = .04) adjusted by age. CONCLUSIONS: Our results suggest that CALR mutation type has prognostic value for the stratification of thrombotic risk in ET patients.
OBJECTIVES: In patients with essential thrombocythemia (ET), after the JAK2V617F driver mutation, mutations in CALR are common (classified as type 1, 52-bp deletion or type 2, 5-bp insertion). CALR mutations have generally been associated with a lower risk of thrombosis. This study aimed to confirm the impact of CALR mutation type on thrombotic risk. METHODS: We retrospectively investigated 983 ET patients diagnosed in Spanish and Polish hospitals. RESULTS: With 7.5 years of median follow-up from diagnosis, 155 patients (15.8%) had one or more thrombotic event. The 5-year thrombosis-free survival (TFS) rate was 83.8%, 91.6% and 93.9% for the JAK2V617F, CALR-type 1 and CALR-type 2 groups, respectively (P = .002). Comparing CALR-type 1 and CALR-type 2 groups, TFS for venous thrombosis was lower in CALR-type 1 (P = .046), with no difference in TFS for arterial thrombosis observed. The cumulative incidence of thrombosis was significantly different comparing JAK2V617F vs CALR-type 2 groups but not JAK2V617F vs CALR-type 1 groups. Moreover, CALR-type 2 mutation was a statistically significant protective factor for thrombosis with respect to JAK2V617F in multivariate logistic regression (OR: 0.45, P = .04) adjusted by age. CONCLUSIONS: Our results suggest that CALR mutation type has prognostic value for the stratification of thrombotic risk in ET patients.