Blood Res.  2016 Jun;51(2):113-121. 10.5045/br.2016.51.2.113.

Baseline renal function as a prognostic indicator in patients with newly diagnosed diffuse large B-cell lymphoma

• Hong J
• Lee S
• Chun G
• Jung JY
• Park J
• Ahn JY
• Cho EK
• Shin DB
• Lee JH

• KMID: 2309213
• DOI: http://doi.org/10.5045/br.2016.51.2.113

Abstract

BACKGROUND
The association between baseline renal impairment (RI) and the prognosis of diffuse large B-cell lymphoma (DLBCL) was previously not defined. The aim of this study was to evaluate the prognostic value of RI in patients with DLBCL treated with three-weekly rituximab plus cyclophosphamide, Adriamycin, vincristine, and prednisolone immunochemotherapy (R-CHOP21).
METHODS
Patients with newly diagnosed de novo DLBCLs treated with ≥1 cycle of R-CHOP21 were analyzed retrospectively. Pretreatment blood samples were collected and the glomerular filtration rate (GFR) was calculated. RI was defined by a GFR of <60 mL/min/1.73 m2 according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
RESULTS
Of the 185 patients enrolled in the present study, 19 patients (10.3%) had RI. The reasons for baseline RI were pre-existing CKD (N=5), acute kidney injury due to either obstruction (N=2) or electrolyte imbalance (N=2) related to DLBCL, and undefined causes (N=10). Patients with baseline RI showed inferior overall survival (OS) compared to those without RI (P<0.001). In multivariate analysis, RI was identified as an International Prognostic Index (IPI)-independent prognostic indicator. A baseline hemoglobin level of <10 g/dL and the presence of RI effectively discriminated a portion of the patients with far inferior event-free survival and OS among the patients having high or high-intermediate risk cancers according to either the standard- or the National Comprehensive Cancer Network-IPI.
CONCLUSION
Pretreatment RI was an independent prognostic marker for inferior OS in patients with DLBCL treated with R-CHOP21 immunochemotherapy.

Keyword

Diffuse large B-cell lymphoma; Renal insufficiency; Prognosis; Rituximab

MeSH Terms

Acute Kidney Injury
B-Lymphocytes*
Cooperative Behavior
Cyclophosphamide
Disease-Free Survival
Doxorubicin
Epidemiology
Glomerular Filtration Rate
Humans
Lymphoma, B-Cell*
Multivariate Analysis
Prednisolone
Prognosis
Renal Insufficiency
Renal Insufficiency, Chronic
Retrospective Studies
Rituximab
Vincristine
Cyclophosphamide
Doxorubicin
Prednisolone
Rituximab
Vincristine

Figure

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  Fig. 1 Kaplan–Meier graphs for overall survival according to (A) the standard International Prognostic Index and (B) the National Comprehensive Cancer Network International Prognostic Index.

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  Fig. 2 Kaplan–Meier graph of the patients analyzed according to renal function.

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  Fig. 3 Kaplan–Meier curves according to subgroups defined by either the standard International Prognostic Index (IPI) (A–C) or the National Comprehensive Cancer Network-IPI (D–F).

Reference

1. Launay-Vacher V. Epidemiology of chronic kidney disease in cancer patients: lessons from the IRMA study group. Semin Nephrol. 2010; 30:548–556. PMID: 21146120.

2. Launay-Vacher V. Cancer and the kidney: individualizing dosage according to renal function. Ann Oncol. 2013; 24:2713–2714. PMID: 24170609.

3. Launay-Vacher V, Oudard S, Janus N, et al. Prevalence of Renal Insufficiency in cancer patients and implications for anticancer drug management: the renal insufficiency and anticancer medications (IRMA) study. Cancer. 2007; 110:1376–1384. PMID: 17634949.

4. Kurita GP, Lundström S, Sjøgren P, et al. Renal function and symptoms/adverse effects in opioid-treated patients with cancer. Acta Anaesthesiol Scand. 2015; 59:1049–1059. PMID: 25943005.

5. Durand JP, Mir O, Coriat R, Cessot A, Pourchet S, Goldwasser F. Validation of the Cochin Risk Index Score (CRIS) for life expectancy prediction in terminally ill cancer patients. Support Care Cancer. 2012; 20:857–864. PMID: 21499844.

6. Gwilliam B, Keeley V, Todd C, et al. Development of prognosis in palliative care study (PiPS) predictor models to improve prognostication in advanced cancer: prospective cohort study. BMJ. 2011; 343:d4920. PMID: 21868477.

7. Zhang K, Lai Y, Axelrod R, et al. Modeling the overall survival of patients with advanced-stage non-small cell lung cancer using data of routine laboratory tests. Int J Cancer. 2015; 136:382–391. PMID: 24866905.

8. Sohal DP, Shrotriya S, Glass KT, et al. Predicting early mortality in resectable pancreatic adenocarcinoma: A cohort study. Cancer. 2015; 121:1779–1784. PMID: 25676016.

9. Smith A, Howell D, Patmore R, Jack A, Roman E. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer. 2011; 105:1684–1692. PMID: 22045184.

10. Yi HG, Kim JS, Suh C, et al. Clinical features and survival outcomes of patients with diffuse large B-cell lymphoma: analysis of web-based data from the Korean Lymphoma Working Party Registry. Blood Res. 2013; 48:115–120. PMID: 23826580.

11. Rosenwald A, Wright G, Chan WC, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002; 346:1937–1947. PMID: 12075054.

12. 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. 2007; 109:1857–1861. PMID: 17105812.

13. Hong J, Woo HS, Kim H, et al. Anemia as a useful biomarker in patients with diffuse large B-cell lymphoma treated with R-CHOP immunochemotherapy. Cancer Sci. 2014; 105:1569–1575. PMID: 25263825.

14. Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007; 25:579–586. PMID: 17242396.

15. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999; 130:461–470. PMID: 10075613.

16. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009; 150:604–612. PMID: 19414839.

17. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002; 39(Suppl 1):S1–266. PMID: 11904577.

18. Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999; 17:1244. PMID: 10561185.

19. Weng PH, Hung KY, Huang HL, Chen JH, Sung PK, Huang KC. Cancer-specific mortality in chronic kidney disease: longitudinal follow-up of a large cohort. Clin J Am Soc Nephrol. 2011; 6:1121–1128. PMID: 21511834.

20. Na SY, Sung JY, Chang JH, et al. Chronic kidney disease in cancer patients: an independent predictor of cancer-specific mortality. Am J Nephrol. 2011; 33:121–130. PMID: 21242672.

21. Iff S, Craig JC, Turner R, et al. Reduced estimated GFR and cancer mortality. Am J Kidney Dis. 2014; 63:23–30. PMID: 23993153.

22. Kim S, Lim CS, Han DC, et al. The prevalence of chronic kidney disease (CKD) and the associated factors to CKD in urban Korea: a population-based cross-sectional epidemiologic study. J Korean Med Sci. 2009; 24(Suppl):S11–S21. PMID: 19194539.

23. Witko-Sarsat V, Friedlander M, Nguyen Khoa T, et al. Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure. J Immunol. 1998; 161:2524–2532. PMID: 9725252.

24. Kaysen GA. The microinflammatory state in uremia: causes and potential consequences. J Am Soc Nephrol. 2001; 12:1549–1557. PMID: 11423586.

25. Wilhelm-Leen ER, Hall YN, K Tamura M, Chertow GM. Frailty and chronic kidney disease: the Third National Health and Nutrition Evaluation Survey. Am J Med. 2009; 122:664–671.e2. PMID: 19559169.

26. Coggins CH. Renal failure in lymphoma. Kidney Int. 1980; 17:847–855. PMID: 7412115.

27. Glassock RJ, Winearls C. Ageing and the glomerular filtration rate: truths and consequences. Trans Am Clin Climatol Assoc. 2009; 120:419–428. PMID: 19768194.

28. Zhou Z, Sehn LH, Rademaker AW, et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood. 2014; 123:837–842. PMID: 24264230.

29. Gutiérrez-García G, Cardesa-Salzmann T, Climent F, et al. Geneexpression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Blood. 2011; 117:4836–4843. PMID: 21441466.