Cancer Res Treat.  2019 Apr;51(2):664-671. 10.4143/crt.2018.358.

Albumin-to-Fibrinogen Ratio as an Independent Prognostic Parameter in Untreated Chronic Lymphocytic Leukemia: A Retrospective Study of 191 Cases

• Zou YX
• Qiao J
• Zhu HY
• Lu RN
• Xia Y
• Cao L
• Wu W
• Jin H
• Liu WJ
• Liang JH
• Wu JZ
• Wang L
• Fan L
• Xu W
• Li JY

• KMID: 2464412
• DOI: http://doi.org/10.4143/crt.2018.358

Abstract

PURPOSE
Chronic lymphocytic leukemia (CLL) is one of the most frequent type of B-cell chronic lymphoproliferative disorders and chronic inflammation takes part in the development of CLL. However, there has been no valid immune biomarker to predict the prognosis of untreated CLL patients.
MATERIALS AND METHODS
In this retrospective study, we analyzed the clinical correlations and prognostic value of albumin-to-fibrinogen ratio (AFR) detected at diagnosis in 191 CLL patients.
RESULTS
The cut-off value of AFR was 9.7 calculated by X-tile. Patients who were more than 65 years old were often accompanied by low level of AFR (p < 0.001). Survival analysis showed that patients with low level of AFR had shorter overall survival (OS) than patients with high level of AFR (p < 0.001). Multivariate analysis illustrated that AFR had a negative impact on OS (p=0.003) and was independent of parameters involved in CLL international prognostic index and other prognostic markers such as CD38 and ZAP-70.
CONCLUSION
These data provide a comprehensive view of AFR and shows that AFR at diagnosis is an adverse prognostic factor in untreated CLL patients.

Keyword

Serum albumin; Fibrinogen; B-cell chronic lymphocytic leukemia; Prognosis

MeSH Terms

B-Lymphocytes
Diagnosis
Fibrinogen
Humans
Inflammation
Leukemia, Lymphocytic, Chronic, B-Cell*
Lymphoproliferative Disorders
Multivariate Analysis
Prognosis
Retrospective Studies*
Serum Albumin
Fibrinogen
Serum Albumin

Figure

• 

  Fig. 1. Kaplan-Meier curves of treatment-free survival (A) and overall survival (B) for different levels of albumin-to-fibrinogen ratio (AFR).

• 

  Fig. 2. Kaplan-Meier curves of overall survival for different levels of albumin-to-fibrinogen ratio (AFR) stratified by age (A), immunoglobulin heavy variable-region (IGHV) mutation status (B), Binet stage (C), tumor protein 53 (TP53) status (D), and β2-microglobulin (β2-MG) level (E).

Reference

References

1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144:646–74.

2. Caligaris-Cappio F. Inflammation, the microenvironment and chronic lymphocytic leukemia. Haematologica. 2011; 96:353–5.

3. Rozovski U, Keating MJ, Estrov Z. Targeting inflammatory pathways in chronic lymphocytic leukemia. Crit Rev Oncol Hematol. 2013; 88:655–66.

4. Wierda WG, O'Brien S, Wang X, Faderl S, Ferrajoli A, Do KA, et al. Prognostic nomogram and index for overall survival in previously untreated patients with chronic lymphocytic leukemia. Blood. 2007; 109:4679–85.

5. Levis A, Ficara F, Marmont F, De Crescenzo A, Resegotti L. Prognostic significance of serum albumin in chronic lymphocytic leukemia. Haematologica. 1991; 76:113–9.

6. Wang Y, Chen W, Hu C, Wen X, Pan J, Xu F, et al. Albumin and fibrinogen combined prognostic grade predicts prognosis of patients with prostate cancer. J Cancer. 2017; 8:3992–4001.

7. Miura K, Hamanaka K, Koizumi T, Kitaguchi Y, Terada Y, Nakamura D, et al. Clinical significance of preoperative serum albumin level for prognosis in surgically resected patients with non-small cell lung cancer: comparative study of normal lung, emphysema, and pulmonary fibrosis. Lung Cancer. 2017; 111:88–95.

8. Wang H, Zhao J, Zhang M, Han L, Wang M, Xingde L. The combination of plasma fibrinogen and neutrophil lymphocyte ratio (F-NLR) is a predictive factor in patients with resectable non small cell lung cancer. J Cell Physiol. 2018; 233:4216–24.

9. Xu WY, Zhang HH, Yang XB, Bai Y, Lin JZ, Long JY, et al. Prognostic significance of combined preoperative fibrinogen and CA199 in gallbladder cancer patients. World J Gastroenterol. 2018; 24:1451–63.

10. Lv GY, Yu Y, An L, Sun XD, Sun DW. Preoperative plasma fibrinogen is associated with poor prognosis in esophageal carcinoma: a meta-analysis. Clin Transl Oncol. 2018; 20:853–61.

11. Li SQ, Jiang YH, Lin J, Zhang J, Sun F, Gao QF, et al. Albumin-to-fibrinogen ratio as a promising biomarker to predict clinical outcome of non-small cell lung cancer individuals. Cancer Med. 2018; 7:1221–31.

12. Wang WT, Zhu HY, Wu YJ, Xia Y, Wu JZ, Wu W, et al. Elevated absolute NK cell counts in peripheral blood predict good prognosis in chronic lymphocytic leukemia. J Cancer Res Clin Oncol. 2018; 144:449–57.

13. Xia Y, Fan L, Wang L, Gale RP, Wang M, Tian T, et al. Frequencies of SF3B1, NOTCH1, MYD88, BIRC3 and IGHV mutations and TP53 disruptions in Chinese with chronic lymphocytic leukemia: disparities with Europeans. Oncotarget. 2015; 6:5426–34.

14. Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bioinformatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004; 10:7252–9.

15. Herishanu Y, Kay S, Sarid N, Kohan P, Braunstein R, Rotman R, et al. Absolute monocyte count trichotomizes chronic lymphocytic leukemia into high risk patients with immune dysregulation, disease progression and poor survival. Leuk Res. 2013; 37:1222–8.

16. Wu HC, Lee LC, Wang WJ. Associations among serum beta 2 microglobulin, malnutrition, inflammation, and advanced cardiovascular event in patients with chronic kidney disease. J Clin Lab Anal. 2017; 31:e22056.

17. Pal S, Bhattacharjee A, Ali A, Mandal NC, Mandal SC, Pal M. Chronic inflammation and cancer: potential chemoprevention through nuclear factor kappa B and p53 mutual antagonism. J Inflamm (Lond). 2014; 11:23.

18. Rothschild MA, Oratz M, Schreiber SS. Serum albumin. Hepatology. 1988; 8:385–401.

19. Emilie D, Leger-Ravet MB, Devergne O, Raphael M, Peuchmaur M, Coumbaras J, et al. Intratumoral production of IL-6 in B cell chronic lymphocytic leukemia and B lymphomas. Leuk Lymphoma. 1993; 11:411–7.

20. Jablonska E, Kiersnowska-Rogowska B, Rogowski F, Parfienczyk A, Puzewska W, Bukin M. TNF family molecules in the serum of patients with B-cell chronic lymphocytic leukemia (B-CLL). Leuk Lymphoma. 2005; 46:1307–12.

21. Krejci P, Dvorakova D, Krahulcova E, Pachernik J, Mayer J, Hampl A, et al. FGF-2 abnormalities in B cell chronic lymphocytic and chronic myeloid leukemias. Leukemia. 2001; 15:228–37.

22. Gora-Tybor J, Blonski JZ, Robak T. Circulating vascular endothelial growth factor (VEGF) and its soluble receptors in patients with chronic lymphocytic leukemia. Eur Cytokine Netw. 2005; 16:41–6.