Does Radiotherapy Augment Natural Killer Cell Function in Pediatric Acute Lymphoblastic Leukemia?

Abstract

Objective: The aim of this study was to investigate changes in natural killer (NK) cell proportion, NK cell activity, and cytokine levels in children with acute lymphoblastic leukemia (ALL) during and after therapy. Materials and Methods: The study group included 33 ALL patients and the control group consisted of 11 healthy children. The ALL patients were divided into three groups, those who had completed protocol M, receiving maintenance chemotherapy, and whose chemotherapy was discontinued. NK cell cytotoxicity was evaluated at different effector to target (E:T) cell ratios and in lytic units (LU). Expression of CD56, CD3, NKp46, CD2, CD94, NKG2D, and CD16 molecules and levels of the interferon gamma (IFN-γ) and interleukin-15 (IL-15) were measured. Results: NK cell activity at an E:T ratio of 1:1 was higher in patients receiving maintenance chemotherapy compared to the other groups (p<0.05), but there was no difference between the groups in LU (p>0.05). The ratio of CD16+CD56+ cells was smaller in the maintenance chemotherapy group compared to controls (p<0.05). Patients who underwent prophylactic cranial irradiation showed significantly higher NK cytotoxicity at 1:1 E:T ratio compared to those who did not (p<0.05). Eighty-three percent of patients in the maintenance chemotherapy group underwent prophylactic cranial irradiation. The IFN-γ levels were significantly lower in the maintenance chemotherapy and discontinued treatment groups compared to the control group (p<0.05). Conclusion: In children with ALL, chemotherapy reduces the NK cell population and IFN-γ levels. The increase in NK cell activity in patients receiving maintenance chemotherapy may be associated with prophylactic cranial radiotherapy.

Keywords

• Acute lymphoblastic leukemia
• children
• interferon
• natural killer cells

Çocukluk Çağı Akut Lenfoblastik Lösemisinde Radyoterapi Doğal Öldürücü Hücre Fonksiyonlarını Artırır Mı?

Abstract

Amaç: Bu çalışmanın amacı, akut lenfoblastik lösemili (ALL) çocuklarda tedavi sırasında ve sonrasında doğal öldürücü (NK) hücre oranı, NK hücre aktivitesi ve sitokin düzeylerindeki değişiklikleri araştırmaktır. Gereç ve Yöntem: Çalışma grubu 33 ALL hastasını ve kontrol grubu 11 sağlıklı çocuktan oluştu. ALL hastaları, M protokolünü tamamlayan, idame kemoterapisi alan ve kemoterapisi kesilen olmak üzere üç gruba ayrıldı. NK hücre sitotoksisitesi, farklı efektör-hedef (E:H) hücre oranlarında ve litik birimlerde (LU) değerlendirildi. CD56, CD3, NKp46, CD2, CD94, NKG2D ve CD16 moleküllerinin ekspresyonu ve interferon gamma (IFN-γ) ve interlökin-15 (IL-15) seviyeleri ölçüldü. Bulgular: 1:1 E:H oranında NK hücre aktivitesi idame kemoterapisi alan hastalarda diğer gruplara göre daha yüksek (p<0.05), ancak litik birimler açısından değerlendirildiğinde gruplar arasında fark saptanmadı (p>0.05). CD16+CD56+ hücrelerin oranı, kontrollere göre idame kemoterapi grubunda daha düşük (p<0.05), profilaktik kraniyal radyoterapi uygulanan hastaların 1:1 E:H oranında NK sitotoksisitesi ise almayanlara göre anlamlı olarak daha yüksek saptandı (p<0.05). İdame kemoterapi grubundaki hastaların %83’üne profilaktik kraniyal ışınlama uygulandı. IFN-γ seviyeleri kontrol grubuna göre idame kemoterapi ve tedavi kesilen gruplarda anlamlı olarak daha düşük saptandı (p<0.05). Sonuç: ALL'li çocuklarda kemoterapi NK hücre sayısını ve IFN-γ düzeylerini azaltır. İdame kemoterapisi alan hastalarda NK hücre aktivitesindeki artış profilaktik kraniyal radyoterapi ile ilişkili olabilir.

Keywords

• akut lenfoblastik lösemi
• çocuk
• interferon
• doğal öldürücü hücreler

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