Turkiye Klinikleri Journal of Medical Sciences

.: ORIGINAL RESEARCH
The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study
Tüylü Hücreli Lösemi Hastalarında BRAF V600E Mutasyonu Sıklığı ve Kladribin Tedavisinin Mutasyon Sıklığı ve Sağkalım Üzerindeki Etkisi: Bir Vaka Kontrol Çalışması
Deniz ÖZMENa , Aynur DAĞLAR ADAYb , Meliha NALÇACIc , Melih AKTANc
aİstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Division of Hematology, İstanbul, Türkiye
bİstanbul University Faculty of Medicine, Department of Medical Genetics, İstanbul, Türkiye
cİstanbul University Faculty of Medicine, Division of Hematology, İstanbul, Türkiye
Turkiye Klinikleri J Med Sci. 2024;44(2):69-75
doi: 10.5336/medsci.2023-98368
Article Language: EN
Full Text
ABSTRACT
 Objective: Hairy cell leukemia (HCL) is a rare and indolent lymphoproliferative disease characterized by the infiltration of hairy shaped leukemic B cells with specific immunophenotypic features in the bone marrow, spleen and liver resulting in progressive pancytopenia and splenomegaly. Purine analogs are preferred as the first-line treatment for HCL. This study investigates the significance of BRAF V600E mutations in HCL diagnosis and prognosis, focusing on their baseline and post-cladribine treatment incidences and impacts on patient survival. Material and Methods: This retrospective, case-control study comprises HCL patients diagnosed and treated between July 2012 and June 2014. The study group includes 22 HCL patients (newly diagnosed n=10, remission n=12). The control group comprises B-cell chronic lymphoproliferative disease patients (n=10). All HCL patients underwent cladribine treatment. Patient demographics, clinical characteristics, and survival outcomes were recorded. Results: The mean age of the predominantly male (81.8%) study group was 51.1±10.2 years. No significant differences in demographic and clinical features existed between the groups (p>0.05). The incidence of BRAF V600E mutation among HCL patients, initially 69.2%, fell to 20% post-treatment. Yet, no significant disparity in overall survival and mortality rates was found between HCL patients with/without BRAF V600E mutation (p=0.256 and p=0.999). Conclusion: The proportion of HCL patients with BRAF V600E mutations decreased from 69.2% to 20% postcladribine. However, persistence of the mutation didn't significantly affect HCL patient survival and mortality.

Keywords: Hairy cell leukemia; BRAF V600E mutation; cladribine; mortality rate; survival
ÖZET
 Amaç: Tüylü hücreli lösemi [hairy cell leukemia (HCL)] splenomegali ve ilerleyici pansitopeni ile seyreden, kemik iliği, dalak ve karaciğerin tüylü görünümlü lösemik B hücreleri ile infiltre olduğu, yavaş seyirli, spesifik immünofenotipik bulgulara sahip, nadir görülen bir hastalıktır. Günümüzde, HCL'nin tedavisinde ilk basamakta pürin analogları tercih edilmektedir. Bu çalışmada, BRAF V600E mutasyonunun HCL tanı ve prognozundaki önemi, kladribin tedavisi öncesi ve sonrası insidansları ve hasta sağkalımı üzerine etkileri araştırılmaktadır. Gereç ve Yöntemler: Bu retrospektif vaka-kontrol çalışmasının popülasyonu, Temmuz 2012-Haziran 2014 arasında tanı ve tedavi gören HCL hastalarından oluşmaktadır. Çalışma grubu 22 HCL hastasını (yeni tanı n=10, remisyon n=12) içerirken, kontrol grubu B hücreli kronik lenfoproliferatif hastalığı olan hastaları (n=10) kapsamaktadır. Tüm HCL hastalarına kladribin tedavisi uygulanmıştır. Hastaların demografik ve klinik özellikleri kaydedilmiştir. Bulgular: Çalışma grubu, ağırlıklı olarak erkek (%81,8) ve ortalama yaş 51,1±10,2 idi. Gruplar arasında demografik ve klinik özelliklerde anlamlı bir fark bulunmamıştır (p>0,05). Başlangıçtaki BRAF V600E mutasyonu pozitifliği oranı %69,2 iken, tedavi sonrası %20'ye düşmüştür. Ancak BRAF V600E mutasyonu olan ve olmayan HCL hastaları arasında genel sağkalım ve ölüm oranlarında belirgin bir fark görülmemiştir (p=0,256 ve p=0,999). Sonuç: Kladribin tedavisi sonrası BRAF V600E mutasyonlu HCL hastalarının oranı %69,2'den %20'ye düşmüştür. Ancak kladribin tedavisi sonrası mutasyonda negatifleşmenin HCL hastalarında sağkalım ve mortalite üzerinde anlamlı bir etkisi bulunmamaktadır.

Anahtar Kelimeler: Tüylü hücreli lösemi; BRAF V600E mutasyonu; kladribin; ölüm oranı; sağkalım
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