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

Year 2025, Volume: 8 Issue: 6, 1112 - 1117, 25.10.2025

İbrahim Ethem Pınar , Vildan Özkocaman , Tuba Ersal , Vildan Gürsoy , Fazıl Çağrı Hunutlu , Elif Yiğit Ayhan , Fahir Özkalemkaş

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

Ethical Statement

This study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Ethics Committee of Bursa Uludag University Faculty of Medicine (Approval No: 2021-7/30; Date: June 2, 2021).

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

Ethical Statement

Bu çalışma, Helsinki Bildirgesi ilkelerine uygun olarak yürütülmüş ve Bursa Uludağ Üniversitesi Tıp Fakültesi Etik Kurulu tarafından onaylanmıştır (Onay No: 2021-7/30; Tarih: 2 Haziran 2021).

References

• Biccler J, Eloranta S, de Nully Brown P, et al. Simplicity at the cost of predictive accuracy in diffuse large B-cell lymphoma: a critical assessment of the R-IPI, IPI, and NCCN-IPI. Cancer Medicine. 2018;7(1): 114-122. doi:10.1002/cam4.1271
• Sehn LH, Berry B, Chhanabhai M, et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2006;109(5):1857-1861. doi:10.1182/blood-2006-08- 038257
• Spiegel JY, Cheung MC, Guirguis HR, Buckstein R. Validation of the NCCN-IPI in both de novo and transformed diffuse large B cell lymphoma. Leukemia Lymphoma. 2017;58(1):214-217. doi:10.1080/10428194.2016.1179295
• Mu S, Shi D, Ai L, et al. International Prognostic Index-based immune prognostic model for diffuse large B-cell lymphoma. Front Immunol. 2021;12:732006. doi:10.3389/fimmu.2021.732006
• Wang J, Zhou M, Xu JY, et al. MYC and BCL-2 adjusted-International Prognostic Index (A-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Histol Histopathol. 2016;31(3):285-292. doi:10.14670/hh-11-673
• Khanmohammadi S, Masrour M, Fallahtafti P, Hasani F. MicroRNA as a potential diagnostic and prognostic biomarker in diffuse large B-cell lymphoma: a systematic review and meta-analysis. Cancer Reports. 2025;8(1):e70070. doi:10.1002/cnr2.70070
• Perry AM, Mitrovic Z, Chan WC. Biological prognostic markers in diffuse large B-cell lymphoma. Cancer Control. 2012;19(3):214-226. doi: 10.1177/107327481201900306
• Peng Y, Jiang T, Chen S, et al. Nutritional and immune-inflammatory scoring system for predicting prognosis in patients with newly diagnosed diffuse large B-cell lymphoma. Blood. 2024;144(Supplement 1): 6463-6463. doi:10.1182/blood-2024-204285
• He J, Yin H, Xia Y, et al. Prognostic Nutritional Index, a novel biomarker which predicts worse prognosis in diffuse large B cell lymphoma. Leukemia Research. 2021;110:106664. doi:10.1016/j.leukres.2021.106664
• Waley AB, Haggag R, Ahmed Barakat AA, et al. Impact of Prognostic Nutritional Index and Systemic Immune-Inflammation Index on the clinical outcome of diffuse large B cell lymphoma patients treated with RCHOP. Zagazig Univ Med J. 2024;30(8.1):3907-3917. doi:10.21608/zumj.2024.256794.3059
• Ersal T, Özkocaman V, Pınar İE, et al. Systemic inflammatory indices for predicting prognosis of myelofibrosis. Sci Rep. 2023;13(1):12539. doi: 10.1038/s41598-023-39077-7
• Gürsoy V, Hunutlu F, Pinar IE, et al. The clinical impacts of the controlling nutritional status score on patients with Hodgkin lymphoma. Eur Rev Med Pharmacol Sci. 2023;27(20):9916-9927. doi:10. 26355/eurrev_202310_34170
• Gursoy V, Sadri S, Kucukelyas HD, et al. HALP score as a novel prognostic factor for patients with myelodysplastic syndromes. Sci Rep. 2024;14(1):13843. doi:10.1038/s41598-024-64166-6
• Ersal T, Ozkocaman V, Pınar İE, et al. Potential prognostic parameters and real-world data in patients with primary central nervous system lymphoma: a new brick on the old ones. Eur Res J. 2023;9(5):1157-1165. doi:10.18621/eurj.1267903
• Hao X, Wei Y, Wei X, et al. Glasgow prognostic score is superior to other inflammation-based scores in predicting survival of diffuse large B-cell lymphoma. Oncotarget. 2017;8(44):76740-76748. doi:10.18632/oncotarget.20832
• Liu T, Ye F, Li Y, Liu A. Comparison and exploration of the prognostic value of the Advanced Lung Cancer Inflammation Index, Prognostic Nutritional Index, and Systemic Immune-Inflammation Index in newly diagnosed diffuse large B-cell lymphoma. Ann Palliat Med. 2021;10(9):9650-9659.
• Go S-I, Park S, Kang MH, Kim H-G, Kim HR, Lee G-W. Clinical impact of Prognostic Nutritional Index in diffuse large B cell lymphoma. Ann Hematol. 2019;98(2):401-411. doi:10.1007/s00277-018-3540-1
• Chen D, Ma Y, Li J, et al. Prognostic and clinicopathological significance of C-reactive protein–albumin–lymphocyte(CALLY) in patients with digestive system neoplasms: a systematic review and meta-analysis. World J Surg Oncol. 2025;23(1):114. doi:10.1186/s12957-025-03779-1
• Liu X-Y, Zhang X, Zhang Q, et al. The value of CRP-Albumin-Lymphocyte Index (CALLY Index) as a prognostic biomarker in patients with non-small cell lung cancer. Support Care Cancer. 2023;31(9):533. doi:10.1007/s00520-023-07997-9
• Feng J, Wang L, Yang X, Chen Q. Clinical significance of preoperative CALLY Index for prognostication in patients with esophageal squamous cell carcinoma undergoing surgery. Sci Rep. 2024;14(1):713. doi:10.1038/s41598-023-51109-w
• Fukushima N, Masuda T, Tsuboi K, et al. Prognostic significance of the preoperative C-reactive protein-albumin-lymphocyte (CALLY) index on outcomes after gastrectomy for gastric cancer. Surgery Today. 2024;54(8):943-952. doi:10.1007/s00595-024-02813-1
• Aoyama T, Maezawa Y, Hashimoto I, et al. The CRP-Albumin-Lymphocyte (CALLY) Index is an independent prognostic factor for gastric cancer patients who receive curative treatment. Anticancer Res. 2024;44(4):1629. doi:10.21873/anticanres.16961
• Wang Z, Zhang J, Luo S, Zhao X. Prognostic significance of Systemic Immune-Inflammation Index in patients with diffuse large B-cell lymphoma. Front Oncol. 2021;11: 655259. doi:10.3389/fonc.2021.655259
• Jelicic J, Juul-Jensen K, Bukumiric Z, et al. Prognostic indices in diffuse large B-cell lymphoma: a population-based comparison and validation study of multiple models. Blood Cancer J. 2023;13(1):157. doi:10.1038/s41408-023-00930-7
• Wu J, Zhu H, Zhang Q, et al. Nomogram based on the systemic immune-inflammation index for predicting the prognosis of diffuse large B-cell lymphoma. Asia-Pacific J Clin Oncol. 2023;19(2):e138-e148. doi:10.1111/ajco.13806
• Shen Z, Wang F, He C, et al. The Value of Prognostic Nutritional Index (PNI) on newly diagnosed diffuse large B-cell lymphoma patients: a multicenter retrospective study of HHLWG based on propensity score matched analysis. J Inflammat Res. 2021;14:5513-5522. doi:10.2147/jir.s340822
• Su F, Lian K. Prognostic evaluation of System Immune-Inflammatory Index and Prognostic Nutritional Index in double expressor diffuse large B-cell lymphoma. Open Medicine. 2023;18(1):20230819. doi:10.1515/med-2023-0819
• Iida H, Tani M, Komeda K, et al. Superiority of CRP-Albumin-Lymphocyte Index (CALLY Index) as a non-invasive prognostic biomarker after hepatectomy for hepatocellular carcinoma. HPB. 2022; 24(1):101-115. doi:10.1016/j.hpb.2021.06.414
• Cherng H-JJ, Herrera A. Circulating Tumor DNA in Diffuse Large B-Cell Lymphoma: from Bench to Bedside? Curr Treat Option Oncol. 2024;25(5):659-678. doi:10.1007/s11864-024-01201-8
• Fu L, Zhou X, Zhang X, et al. Circulating tumor DNA in lymphoma: technologies and applications. J Hematol Oncol. 2025;18(1):29. doi:10. 1186/s13045-025-01673-7
• Pinar IE, Ozkocaman V, Ersal T, et al. Comparison of international prognostic indices and validation study for patients with diffuse large B-cell lymphoma in the Rituximab Era. Article. Uluslararasi Hematol Onkol Derg. 2023;33(2):57-65. doi:10.4999/uhod.236953
• Demirci U, Kırkızlar HO, Ümit EG, et al. CD5 as a prognostic marker in patients with diffuse large B-cell lymphoma: a multicenter study. J Hematopathol. 2022;15(4):203-213. doi:10.1007/s12308-022-00523-6