Impact of CALR and JAK2V617F Mutations on Clinical Course and Disease Outcomes in Essential Thrombocythemia: A Multicenter Retrospective Study in Turkish PatientsZehra Narlı Özdemir1, Yıldız İpek2, Pusem Patir3, Gözde Ermiş4, Rafiye Çiftçiler5, Deniz Özmen6, Mehmet Baysal7, Vildan Gürsoy8, Esra Yıldızhan9, Serkan Güven10, Tarık Ercan11, Tayfun Elibol12, Sinan Mersin13, Eylem Genç14, Eren Arslan Davulcu15, Volkan Karakuş3, Nergiz Erkut4, Gürsel Güneş16, Reyhan Diz Küçükkaya17, Ahmet Emre Eşkazan61İzmir City Hospital, Clinic of Hematology, İzmir, Türkiye
2Kartal Dr. Lüfti Kırdar City Hospital, Clinic of Hematology, İstanbul, Türkiye
3Antalya Training and Research Hospital, Clinic of Hematology, Antalya, Türkiye
4Karadeniz Technical University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Trabzon, Türkiye
5Selçuk University Faculty of Medicine, Department of Hematology, Konya, Türkiye
6İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Internal Medicine, Division of Hematology, İstanbul, Türkiye
7Ali Osman Sönmez Oncology Hospital, Clinic of Hematology, Bursa, Türkiye
8Bursa City Hospital, Clinic of Orthopedics and Traumatology, Bursa, Türkiye
9Kayseri City Hospital, Clinic of Hematology, Kayseri, Türkiye
10Mehmet Akif Ersoy State Hospital, Clinic of Hematology, Çanakkale, Türkiye
11Haydarpaşa Numune Training and Research Hospital, Clinic of Hematology, İstanbul, Türkiye
12Medeniyet University Göztepe Training and Research Hospital, Clinic of Hematology, İstanbul, Türkiye
13Muğla Sıtkı Koçman University Training and Research Hospital, Clinic of Hematology, Muğla, Türkiye
14Tekirdağ Dr. İsmail Fehmi Cumalıoğlu City Hospital, Clinic of Hematology, Tekirdağ, Türkiye
15University of Health Sciences Türkiye, İstanbul Bakırköy Dr. Sadi Konuk Training and Research Hospital, Clinic of Hematology, İstanbul, Türkiye
16University of Health Sciences Türkiye, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Clinic of Hematology, Ankara, Türkiye
17İstanbul University Faculty of Science, Department of Molecular Biology and Genetics, İstanbul, Türkiye
Objective: In this study, we investigated the effects of calreticulin (CALR) and JAK2V617F mutational status on clinical course and disease outcomes in Turkish patients with essential thrombocythemia (ET).
Materials and Methods: Seventeen centers from Türkiye participated in the study and CALR- and JAK2V617F-mutated ET patients were evaluated retrospectively.
Results: A total of 302 patients were included, of whom 203 (67.2%) and 99 (32.8%) were JAK2V617F- and CALR-positive, respectively. CALR-mutated patients were significantly younger (51 years vs. 57.5 years, p=0.03), with higher median platelet counts (987x109/L vs. 709x109/L, p<0.001) and lower median hemoglobin levels (13.1 g/dL vs. 14.1 g/dL, p<0.001) compared to JAK2V617F-mutated patients. Thromboembolic events (TEEs) occurred in 54 patients (17.9%), 77.8% of which were arterial. Compared to CALR mutation, JAK2V617F was associated with a higher risk of thrombosis (8.1% vs. 22.7%, p=0.002). Rates of transformation to myelofibrosis (MF) and leukemia were 4% and 0.7%, respectively, and these rates were comparable between JAK2V617F- and CALR-mutated cases. The estimated overall survival (OS) and MF-free survival of the entire cohort were 265.1 months and 235.7 months, respectively. OS and MF-free survival durations were similar between JAK2V617F- and CALR-mutated patients. Thrombosis-free survival (TFS) was superior in CALR-mutated patients compared to JAK2V617F-positive patients (5-year TFS: 90% vs. 71%, respectively; p=0.001). Age at diagnosis was an independent factor affecting the incidence of TEEs.
Conclusion: In our ET cohort, CALR mutations resulted in higher platelet counts and lower hemoglobin levels than JAK2V617F and were associated with younger age at diagnosis. JAK2V617F was strongly associated with thrombosis and worse TFS. Hydroxyurea was the most preferred cytoreductive agent for patients with high thrombosis risk.
Keywords: CALR mutation, Essential thrombocythemia, JAK2V617F mutation, Myeloproliferative neoplasm
Esansiyel Trombositemide CALR ve JAK2V617F Mutasyonlarının Klinik Seyir ve Hastalık Sonuçlarına Etkisi: Türk Hastalarda Geriye Dönük Çok Merkezli ÇalışmaZehra Narlı Özdemir1, Yıldız İpek2, Pusem Patir3, Gözde Ermiş4, Rafiye Çiftçiler5, Deniz Özmen6, Mehmet Baysal7, Vildan Gürsoy8, Esra Yıldızhan9, Serkan Güven10, Tarık Ercan11, Tayfun Elibol12, Sinan Mersin13, Eylem Genç14, Eren Arslan Davulcu15, Volkan Karakuş3, Nergiz Erkut4, Gürsel Güneş16, Reyhan Diz Küçükkaya17, Ahmet Emre Eşkazan61İzmir City Hospital, Clinic of Hematology, İzmir, Türkiye
2Kartal Dr. Lüfti Kırdar City Hospital, Clinic of Hematology, İstanbul, Türkiye
3Antalya Training and Research Hospital, Clinic of Hematology, Antalya, Türkiye
4Karadeniz Technical University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Trabzon, Türkiye
5Selçuk University Faculty of Medicine, Department of Hematology, Konya, Türkiye
6İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Internal Medicine, Division of Hematology, İstanbul, Türkiye
7Ali Osman Sönmez Oncology Hospital, Clinic of Hematology, Bursa, Türkiye
8Bursa City Hospital, Clinic of Orthopedics and Traumatology, Bursa, Türkiye
9Kayseri City Hospital, Clinic of Hematology, Kayseri, Türkiye
10Mehmet Akif Ersoy State Hospital, Clinic of Hematology, Çanakkale, Türkiye
11Haydarpaşa Numune Training and Research Hospital, Clinic of Hematology, İstanbul, Türkiye
12Medeniyet University Göztepe Training and Research Hospital, Clinic of Hematology, İstanbul, Türkiye
13Muğla Sıtkı Koçman University Training and Research Hospital, Clinic of Hematology, Muğla, Türkiye
14Tekirdağ Dr. İsmail Fehmi Cumalıoğlu City Hospital, Clinic of Hematology, Tekirdağ, Türkiye
15University of Health Sciences Türkiye, İstanbul Bakırköy Dr. Sadi Konuk Training and Research Hospital, Clinic of Hematology, İstanbul, Türkiye
16University of Health Sciences Türkiye, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Clinic of Hematology, Ankara, Türkiye
17İstanbul University Faculty of Science, Department of Molecular Biology and Genetics, İstanbul, Türkiye
Amaç: Bu çalışmada Türk esansiyel trombositemi (ET) hastalarında CALR ve JAK2V617F mutasyon durumunun klinik seyir ve hastalık sonuçlarına etkilerini araştırdık.
Gereç ve Yöntem: Çalışmaya Türkiye’den 17 merkez katılmış olup, CALR ve JAK2V617F mutasyonu pozitif olan ET hastaları geriye dönük olarak değerlendirilmiştir.
Bulgular: Çalışmaya toplam 302 hasta dahil edildi. Bunların 203’ü (%67,2) JAK2V617F ve 99’u (%32,8) CALR pozitifti. CALR mutasyonlu hastalar JAK2V617F pozitif olanlara göre daha gençti (sırasıyla; 51 yaş, 57,5 yaş, p=0,03), daha yüksek ortanca trombosit sayısına (sırasıyla; 987x109/L, 709x109/L, p<0,001) ve daha düşük ortanca hemoglobin düzeylerine (sırasıyla; 13,1 g/dL, 14,1 g/dL, p<0,001) sahipti. Tromboembolik olaylar (TEO) 54 hastada (%17,9) meydana geldi ve bunların %77,8’i arteriyeldi. CALR mutasyonu ile karşılaştırıldığında JAK2 V617F daha yüksek tromboz riski ile ilişkiliydi (%8,1’e karşı %22,7, p=0,002). Miyelofibroz (MF) ve lösemiye dönüşüm oranları sırasıyla %4 ve %0,7 idi ve bu oranlar JAK2V617F ve CALR mutasyonlu olgular arasında benzerdi. Tüm kohortta tahmini toplam sağkalım (OS) ve MF’siz sağkalım sırasıyla 265,1 ay ve 235,7 aydı. JAK2V617F ve CALR mutasyonlu hastalar arasında OS ve MF’siz sağkalım benzerdi. CALR mutasyonlu vakalarda trombozsuz sağkalım (TFS), JAK2V617F pozitif hastalara göre daha üstündü (5 yıllık TFS sırasıyla; %90, %71 [p=0,001]). Tanı yaşı TEO insidansını etkileyen bağımsız bir faktördü.
Sonuç: ET kohortumuzda CALR mutasyonları, JAK2V617F’ye göre daha yüksek trombosit sayısı, daha düşük hemoglobin düzeyi ve tanı anında daha genç yaşla ilişki bulundu. JAK2V617F, tromboz ve daha kötü TFS ile güçlü bir şekilde ilişkiliydi. Hidroksiüre yüksek tromboz riski olan hastalarda en çok tercih edilen sitoredüktif ilaçtı.
Anahtar Kelimeler: CALR mutasyonu, Esansiyel trombositemi, JAK2V617F mutasyonu, Miyeloproliferatif neoplazm
Zehra Narlı Özdemir, Yıldız İpek, Pusem Patir, Gözde Ermiş, Rafiye Çiftçiler, Deniz Özmen, Mehmet Baysal, Vildan Gürsoy, Esra Yıldızhan, Serkan Güven, Tarık Ercan, Tayfun Elibol, Sinan Mersin, Eylem Genç, Eren Arslan Davulcu, Volkan Karakuş, Nergiz Erkut, Gürsel Güneş, Reyhan Diz Küçükkaya, Ahmet Emre Eşkazan. Impact of CALR and JAK2V617F Mutations on Clinical Course and Disease Outcomes in Essential Thrombocythemia: A Multicenter Retrospective Study in Turkish Patients. Turk J Hematol. 2024; 41(1): 26-36
Corresponding Author: Zehra Narlı Özdemir |
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