Immunonutritional profiling for prognostic assessment in diffuse large B-cell lymphoma: an initial evaluation of the C-reactive Protein–Albumin–Lymphocyte (CALLY) Index

Abstract

Aims: Diffuse large B-cell lymphoma (DLBCL) demonstrates wide heterogeneity, complicating risk stratification with conventional prognostic instruments, particularly the International Prognostic Index (IPI). The C-reactive Protein (CRP)-Albumin-Lymphocyte (CALLY) Index, an immunonutritional marker that integrates inflammation, nutritional status, and immune competence, has demonstrated prognostic relevance in solid tumors. The present analysis was designed to determine the clinical utility of the CALLY Index for prognostication in newly diagnosed DLBCL patients and to assess its added value when integrated with traditional prognostic scores. Methods: In this retrospective cohort, 112 patients presenting with newly diagnosed DLBCL and treated at Bursa Uludağ University between 2015 and 2019 were evaluated. The CALLY Index was calculated as (serum albumin × absolute lymphocyte count) / (CRP×10⁴). An optimal cutoff value of 0.78 was derived using log-rank testing and used to stratify patients into low (≤0.78) and high (>0.78) CALLY categories. Baseline clinical features were compared between groups. Kaplan-Meier curves and multivariable Cox proportional hazards modeling were applied to examine overall survival (OS). Multivariable analysis included IPI score and serum beta-2-microglobulin. Results: Cases in the low CALLY subgroup (68.8%) were significantly older, had poorer Eastern Cooperative Oncology Group performance, lower albumin, higher CRP, and more advanced disease (p<0.01 for all). They were also more frequently classified into higher-risk IPI categories (p=0.009). Median OS in the low CALLY group was 14.8 months, while the high CALLY group had not reached median OS at the end of follow-up (p=0.0009). Univariable analysis revealed that low CALLY (HR: 5.33, p=0.002) and high IPI score were associated with worse OS. In multivariable analysis, low CALLY remained an independent predictor of mortality (HR: 3.42, 95% CI: 1.16-10.08; p=0.025), even after adjusting for IPI and beta-2-microglobulin levels. Conclusion: The CALLY Index is an independent and clinically accessible prognostic biomarker in DLBCL. Its integration of inflammatory, nutritional, and immune parameters provides complementary prognostic information beyond traditional models such as the IPI. Given its cost-effectiveness and reliance on routine laboratory data, the CALLY Index may serve as a valuable tool in real-world prognostic assessment. These findings support prospective validation and exploration of its utility in dynamic risk models and personalized treatment strategies for DLBCL

Keywords

• Diffuse large B-cell lymphoma
• CALLY Index
• immunonutritional profiling
• prognosis
• International Prognostic Index
• overall survival

Diffüz büyük B hücreli lenfomada prognostik değerlendirme için immünonütrisyonel profilleme: C-reaktif Protein–Albümin–Lenfosit (CALLY) İndeksinin ilk değerlendirmesi

Abstract

Amaç: Diffüz büyük B hücreli lenfoma (DBBHL), belirgin heterojenite gösteren bir hastalık olup, özellikle Uluslararası Prognostik İndeks (IPI) gibi geleneksel prognostik araçlarla risk sınıflamasını güçleştirmektedir. İnflamasyon, beslenme durumu ve immün yanıtı bir araya getiren immünonütrisyonel bir belirteç olan C-reaktif protein (CRP)–albümin–lenfosit (CALLY) indeksi, solid tümörlerde prognostik değer göstermiştir. Bu analiz, CALLY indeksinin yeni tanı almış DBBHL hastalarında prognostik değerini belirlemeyi ve klasik prognostik skorlarla birlikte kullanıldığında ek katkısını değerlendirmeyi amaçlamıştır. Yöntemler: 2015–2019 yılları arasında Bursa Uludağ Üniversitesi’nde tedavi edilen ve yeni tanı almış 112 DBBHL hastası retrospektif olarak incelendi. CALLY indeksi şu şekilde hesaplandı: (serum albümin × mutlak lenfosit sayısı) / (CRP × 10⁴). Log-rank testi ile optimal kesim noktası 0,78 olarak belirlendi ve hastalar düşük (≤0,78) ve yüksek (>0,78) CALLY gruplarına ayrıldı. Başlangıç klinik özellikleri gruplar arasında karşılaştırıldı. Genel sağkalım (OS) Kaplan–Meier yöntemiyle değerlendirildi ve çok değişkenli Cox regresyon modeli ile analiz edildi. Çok değişkenli modele IPI skoru ve serum beta-2-mikroglobulin düzeyleri dahil edildi. Bulgular: Düşük CALLY grubundaki hastalar (%68,8) anlamlı olarak daha ileri yaşta, düşük performans skoruna sahip, daha düşük albümin düzeyleri, daha yüksek CRP değerleri ve daha ileri evre hastalık ile karakterizeydi (tümünde p < 0,01). Ayrıca bu grup daha yüksek riskli IPI kategorilerinde daha sık yer almaktaydı (p = 0,009). Düşük CALLY grubunda medyan OS 14,8 ay iken, yüksek CALLY grubunda takip sonunda medyan OS’ye ulaşılamadı (p = 0,0009). Tek değişkenli analizde düşük CALLY (HR: 5,33; p = 0,002) ve yüksek IPI skoru, kötü OS ile ilişkili bulundu. Çok değişkenli analizde ise IPI ve beta-2-mikroglobulin düzeyleri için düzeltme yapıldıktan sonra bile düşük CALLY, bağımsız bir mortalite prediktörü olarak kaldı (HR: 3,42; %95 GA: 1,16–10,08; p = 0,025). Sonuç: CALLY indeksi, DBBHL’de bağımsız ve klinikte kolay uygulanabilir bir prognostik biyobelirteçtir. İnflamatuvar, beslenme ve immün parametreleri birleştirmesi sayesinde, IPI gibi geleneksel modellerin ötesinde tamamlayıcı prognostik bilgi sağlar. Düşük maliyetli olması ve rutin laboratuvar verilerine dayanması, CALLY indeksini gerçek yaşam pratiğinde değerli bir araç haline getirmektedir. Bulgularımız, prospektif doğrulama çalışmalarını ve CALLY indeksinin dinamik risk modelleri ile kişiselleştirilmiş tedavi stratejilerindeki potansiyel rolünün araştırılmasını desteklemektedir.

Keywords

• Diffüz büyük B hücreli lenfoma
• CALLY indeksi
• Prognoz
• İmmünonütrisyonel biyobelirteç
• Uluslararası Prognostik İndeks
• Genel sağkalım

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