Ümit ÜRE, M. Cem AR, zafer BAŞLAR, Teoman SOYSAL, Şeniz ÖZGÖREN, Muhterem GÜLSEVEN, Yıldız AYDIN, Birsen ÜLKÜ, Nükhet TÜZÜNER, AHMET BURHAN FERHANOĞLU

The effect of ZAP-70 expression on disease progression in early-stage (Binet A) B-CLL patients

Amaç: Kronik lenfositik lösemi (KLL) değişken klinik bulgular gösterebilen heterojen bir hastalıktır. Erken evre KLL'de klinik seyri önceden gösterebilecek prognostik belirteçler tedavi planlanmasında belirleyici rol oynayabilir. Çeşitli çalışmalarda zeta ilişkili protein 70'in (ZAP-70) önemli bir prognostik gösterge olabileceğine dair veriler elde edilmiştir. Tek merkezli ve retrospektif olarak planlanmış bu çalışmada erken evre B-KLL hastalarında ZAP- 70'in hastalık progresyonu üzerine etkisi araştırılmıştır. Hastalar ve Yöntemler: Ortanca yaşı 66 (dağılım 47-86) olan 50 erken evre B-KLL hastası çalışmaya dahil edildi. ZAP-70 ekspresyon düzeyleri çevresel kanda akım sitometri yöntemi ile çalışıldı. ZAP-70 pozitifliği için eşik değer %20 olarak belirlendi. Bulgular: Ortanca 42 aylık izlemde çalışmaya alınan 50 hastadan 21'inde tedavi gerekliliği ortaya çıktı. Tanıdan tedaviye kadar geçen ortanca süre 24 aydı. Elli hastanın 12'sinde (%24) ZAP-70 pozitif bulundu. ZAP-pozitif gruptaki 12 hastanın 10'unda (%83) ve ZAP-negatif gruptaki 38 hastanın 11'inde (%29) izlem sırasında tedavi başlanması gerekti. ZAP pozitif ve negatif gruplarda tedaviye kadar geçen ortanca süre sırasıyla 25 ve 72 aydı (p=0.0001). Sonuç: Erken evre B-KLL hastalarında tedavi gerekliliğini belirlemede ZAP-70 düzeylerinin önemli prognostik değeri olduğu görülmektedir. Tamamlayıcı çalışmalar ZAP-70 pozitif erken evre hastalarda farklı bir tedavi politikasının gerekli olup olmadığını ortaya koyacaktır.

Anahtar Kelimeler:

Lösemi, lenfositik, kronik, B hücreli, ZAP-70 Protein-Tirozin kinaz, Seyir, Geriyedönük çalışma, Akım sitometrisi, Hastalık ilerlemesi

Erken evre (Binet A) B-KLL hastalarında ZAP-70 ekspresyonunun hastalık progresyonuna etkisi

Objectives: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with various clinical findings. Prognostic markers predicting the clinical outcome in early-stage CLL would play a major role in disease management. Various studies have shown that zetaassociated protein 70 (ZAP-70) provides significant prognostic information. This retrospective, single-centre study evaluates the effect of ZAP-70 on disease progression in early-stage B-CLL. Patients and Methods: Fifty early-stage patients with a median age of 66 years (range 47-86 years) were enrolled in this study. ZAP-70 expression was measured in peripheral blood samples using flow cytometry. Cut-off value for ZAP-70 positivity was set at 20%. Results: Treatment had to be initiated in 21 of the 50 patients within a median of 42 months. The median time to initial treatment was 24 months. Twelve of the 50 patients (24%) were ZAP-70 positive. Ten of the 12 patients (83%) in the ZAP(+) group and 11 of the 38 patients (29%) in the ZAP(-) group required treatment on follow-up. The median treatment-free interval in ZAP(+) and ZAP(-) groups were 25 and 72 months, respectively (p=0.0001). Conclusion: ZAP-70 provides significant prognostic information and predicts treatment requirement in earlystage B-CLL patients. Ongoing studies will highlight the need for a different management policy of ZAP-70(+) early-stage CLL.

Keywords:

Leukemia, Lymphocytic, Chronic, B-Cell, ZAP-70 Protein-Tyrosine Kinase, Prognosis, Retrospective Studies, Flow Cytometry, Disease Progression,

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