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Erschienen in: International Journal of Hematology 4/2016

08.07.2016 | Original Article

Low prognostic nutritional index predicts poor outcome in diffuse large B-cell lymphoma treated with R-CHOP

verfasst von: Qinjun Zhou, Yongqiang Wei, Fen Huang, Xiaolei Wei, Qi Wei, Xiaoxiao Hao, Yuankun Zhang, Ru Feng

Erschienen in: International Journal of Hematology | Ausgabe 4/2016

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Abstract

Prognostic nutritional index (PNI), based on serum albumin concentration and the absolute peripheral lymphocyte count, has been used to predict survival in various tumors. Whether PNI can predict prognosis in patients with diffuse large B-cell lymphoma (DLBCL) remains unknown. We retrospectively analyzed 253 patients with newly diagnosed DLBCL in the present study. The PNI was calculated as: albumin (g/L) + 5 × total lymphocyte count × 109/L. All patients were divided in low and high groups according to the analysis of receiver operating characteristic (ROC) curve. Low PNI was associated with more unfavorable clinical features (p < 0.05). Patients with low PNI tended to have worse event-free survival (EFS) and overall survival (OS) (EFS, p = 0.001; OS, p < 0.001). For patients treated with R-CHOP, PNI proved to be predictive for survival (EFS, p = 0.001; OS, p < 0.001), while no significant effect was found in DLBCL patients who received CHOP chemotherapy (EFS, p = 0.496; OS, p = 0.125). Multivariate analysis showed that low PNI is an independent adverse predictor of OS and EFS, especially in DLBCL patients treated with R-CHOP. In conclusion, this study suggests that PNI is an effective prognostic factor in DLBCL patients treated with R-CHOP.
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Literatur
1.
Zurück zum Zitat Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117(19):5019–32.CrossRefPubMedPubMedCentral Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117(19):5019–32.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Cultrera JL, Dalia SM. Diffuse large B-cell lymphoma: current strategies and future directions. Cancer Control J Moffitt Cancer Center. 2012;19(3):204–13. Cultrera JL, Dalia SM. Diffuse large B-cell lymphoma: current strategies and future directions. Cancer Control J Moffitt Cancer Center. 2012;19(3):204–13.
3.
Zurück zum Zitat Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, MacPherson N, O’Reilly S, Spinelli JJ, Sutherland J, Wilson KS, Gascoyne RD, Connors JM. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23(22):5027–33.CrossRef Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, MacPherson N, O’Reilly S, Spinelli JJ, Sutherland J, Wilson KS, Gascoyne RD, Connors JM. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23(22):5027–33.CrossRef
4.
Zurück zum Zitat Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(4):235–42.CrossRefPubMed Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(4):235–42.CrossRefPubMed
5.
Zurück zum Zitat Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, Klasa R, Savage KJ, Shenkier T, Sutherland J, Gascoyne RD, Connors JM. 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(5):1857–61.CrossRefPubMed Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, Klasa R, Savage KJ, Shenkier T, Sutherland J, Gascoyne RD, Connors JM. 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(5):1857–61.CrossRefPubMed
6.
Zurück zum Zitat Seki R, Ohshima K, Fujisaki T, Uike N, Kawano F, Gondo H, Makino S, Eto T, Moriuchi Y, Taguchi F, Kamimura T, Tsuda H, Ogawa R, Shimoda K, Yamashita K, Suzuki K, Suzushima H, Tsukazaki K, Higuchi M, Utsunomiya A, Iwahashi M, Imamura Y, Tamura K, Suzumiya J, Yoshida M, Abe Y, Matsumoto T, Okamura T. Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era. Cancer Sci. 2009;100(10):1842–7.CrossRefPubMed Seki R, Ohshima K, Fujisaki T, Uike N, Kawano F, Gondo H, Makino S, Eto T, Moriuchi Y, Taguchi F, Kamimura T, Tsuda H, Ogawa R, Shimoda K, Yamashita K, Suzuki K, Suzushima H, Tsukazaki K, Higuchi M, Utsunomiya A, Iwahashi M, Imamura Y, Tamura K, Suzumiya J, Yoshida M, Abe Y, Matsumoto T, Okamura T. Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era. Cancer Sci. 2009;100(10):1842–7.CrossRefPubMed
7.
Zurück zum Zitat Buzby GP, Mullen JL, Matthews DC, Hobbs CL, Rosato EF. Prognostic nutritional index in gastrointestinal surgery. Am J Surg. 1980;139(1):160–7.CrossRefPubMed Buzby GP, Mullen JL, Matthews DC, Hobbs CL, Rosato EF. Prognostic nutritional index in gastrointestinal surgery. Am J Surg. 1980;139(1):160–7.CrossRefPubMed
8.
Zurück zum Zitat Pinato DJ, North BV, Sharma R. A novel, externally validated inflammation-based prognostic algorithm in hepatocellular carcinoma: the prognostic nutritional index (PNI). Br J Cancer. 2012;106(8):1439–45.CrossRefPubMedPubMedCentral Pinato DJ, North BV, Sharma R. A novel, externally validated inflammation-based prognostic algorithm in hepatocellular carcinoma: the prognostic nutritional index (PNI). Br J Cancer. 2012;106(8):1439–45.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Jiang N, Deng JY, Ding XW, Ke B, Liu N, Zhang RP, Liang H. Prognostic nutritional index predicts postoperative complications and long-term outcomes of gastric cancer. World J Gastroenterol WJG. 2014;20(30):10537–44.CrossRefPubMed Jiang N, Deng JY, Ding XW, Ke B, Liu N, Zhang RP, Liang H. Prognostic nutritional index predicts postoperative complications and long-term outcomes of gastric cancer. World J Gastroenterol WJG. 2014;20(30):10537–44.CrossRefPubMed
10.
Zurück zum Zitat Hong S, Zhou T, Fang W, Xue C, Hu Z, Qin T, Tang Y, Chen Y, Ma Y, Yang Y, Hou X, Huang Y, Zhao H, Zhao Y, Zhang L. The prognostic nutritional index (PNI) predicts overall survival of small-cell lung cancer patients. Tumour Biol J Int Soc Oncodev Biol Med. 2015;36(5):3389–97.CrossRef Hong S, Zhou T, Fang W, Xue C, Hu Z, Qin T, Tang Y, Chen Y, Ma Y, Yang Y, Hou X, Huang Y, Zhao H, Zhao Y, Zhang L. The prognostic nutritional index (PNI) predicts overall survival of small-cell lung cancer patients. Tumour Biol J Int Soc Oncodev Biol Med. 2015;36(5):3389–97.CrossRef
11.
Zurück zum Zitat Yang Z, Zhang B, Hou L, Xie Y, Cao X. Pre-operative prognostic nutritional index predicts the outcomes for triple-negative breast cancer. Tumour Biol J Int Soc Oncodev Biol Med. 2014;35(12):12165–71.CrossRef Yang Z, Zhang B, Hou L, Xie Y, Cao X. Pre-operative prognostic nutritional index predicts the outcomes for triple-negative breast cancer. Tumour Biol J Int Soc Oncodev Biol Med. 2014;35(12):12165–71.CrossRef
12.
Zurück zum Zitat Chen KL, Liu YH, Li WY, Chen J, Gu YK, Geng QR, Jiang WQ, Huang HQ, Lin TY, Xia ZJ, Cai QQ. The prognostic nutritional index predicts survival for patients with extranodal natural killer/T cell lymphoma, nasal type. Ann Hematol. 2015;94(8):1389–400.CrossRefPubMed Chen KL, Liu YH, Li WY, Chen J, Gu YK, Geng QR, Jiang WQ, Huang HQ, Lin TY, Xia ZJ, Cai QQ. The prognostic nutritional index predicts survival for patients with extranodal natural killer/T cell lymphoma, nasal type. Ann Hematol. 2015;94(8):1389–400.CrossRefPubMed
13.
Zurück zum Zitat Cueto Manzano AM. Hypoalbuminemia in dialysis. Is it a marker for malnutrition or inflammation? Rev Invest Clin Organo Hosp Enferm Nutr. 2001;53(2):152–8. Cueto Manzano AM. Hypoalbuminemia in dialysis. Is it a marker for malnutrition or inflammation? Rev Invest Clin Organo Hosp Enferm Nutr. 2001;53(2):152–8.
14.
Zurück zum Zitat Don BR, Kaysen G. Serum albumin: relationship to inflammation and nutrition. Semin Dial. 2004;17(6):432–7.CrossRefPubMed Don BR, Kaysen G. Serum albumin: relationship to inflammation and nutrition. Semin Dial. 2004;17(6):432–7.CrossRefPubMed
15.
Zurück zum Zitat McMillan DC, Watson WS, O’Gorman P, Preston T, Scott HR, McArdle CS. Albumin concentrations are primarily determined by the body cell mass and the systemic inflammatory response in cancer patients with weight loss. Nutr Cancer. 2001;39(2):210–3.CrossRefPubMed McMillan DC, Watson WS, O’Gorman P, Preston T, Scott HR, McArdle CS. Albumin concentrations are primarily determined by the body cell mass and the systemic inflammatory response in cancer patients with weight loss. Nutr Cancer. 2001;39(2):210–3.CrossRefPubMed
16.
Zurück zum Zitat Bairey O, Shacham-Abulafia A, Shpilberg O, Gurion R. Serum albumin level at diagnosis of diffuse large B-cell lymphoma: an important simple prognostic factor. Hematol Oncol (2015). Bairey O, Shacham-Abulafia A, Shpilberg O, Gurion R. Serum albumin level at diagnosis of diffuse large B-cell lymphoma: an important simple prognostic factor. Hematol Oncol (2015).
17.
Zurück zum Zitat Dalia S, Chavez J, Little B, Bello C, Fisher K, Lee JH, Chervenick P, Sokol L, Sotomayor E, Shah B. Serum albumin retains independent prognostic significance in diffuse large B-cell lymphoma in the post-rituximab era. Ann Hematol. 2014;93(8):1305–12.CrossRefPubMed Dalia S, Chavez J, Little B, Bello C, Fisher K, Lee JH, Chervenick P, Sokol L, Sotomayor E, Shah B. Serum albumin retains independent prognostic significance in diffuse large B-cell lymphoma in the post-rituximab era. Ann Hematol. 2014;93(8):1305–12.CrossRefPubMed
18.
Zurück zum Zitat Kim DH, Baek JH, Chae YS, Kim YK, Kim HJ, Park YH, Song HS, Chung JS, Hyun MS, Sohn SK. Absolute lymphocyte counts predicts response to chemotherapy and survival in diffuse large B-cell lymphoma. Leukemia. 2007;21(10):2227–30.CrossRefPubMed Kim DH, Baek JH, Chae YS, Kim YK, Kim HJ, Park YH, Song HS, Chung JS, Hyun MS, Sohn SK. Absolute lymphocyte counts predicts response to chemotherapy and survival in diffuse large B-cell lymphoma. Leukemia. 2007;21(10):2227–30.CrossRefPubMed
19.
Zurück zum Zitat Behl D, Ristow K, Markovic SN, Witzig TE, Habermann TM, Colgan JP, Inwards DJ, White WL, Ansell SM, Micallef IN, Johnston PB, Porrata LF. Absolute lymphocyte count predicts therapeutic efficacy of rituximab therapy in follicular lymphomas. Br J Haematol. 2007;137(5):409–15.CrossRefPubMed Behl D, Ristow K, Markovic SN, Witzig TE, Habermann TM, Colgan JP, Inwards DJ, White WL, Ansell SM, Micallef IN, Johnston PB, Porrata LF. Absolute lymphocyte count predicts therapeutic efficacy of rituximab therapy in follicular lymphomas. Br J Haematol. 2007;137(5):409–15.CrossRefPubMed
20.
Zurück zum Zitat Wei X, Huang F, Wei Y, Jing H, Xie M, Hao X, Feng R. Low lymphocyte-to-monocyte ratio predicts unfavorable prognosis in non-germinal center type diffuse large B-cell lymphoma. Leuk Res. 2014;38(6):694–8.CrossRefPubMed Wei X, Huang F, Wei Y, Jing H, Xie M, Hao X, Feng R. Low lymphocyte-to-monocyte ratio predicts unfavorable prognosis in non-germinal center type diffuse large B-cell lymphoma. Leuk Res. 2014;38(6):694–8.CrossRefPubMed
21.
Zurück zum Zitat Wei X, Wei Y, Huang F, Jing H, Xie M, Hao X, Feng R. Lymphopenia predicts preclinical relapse in the routine follow-up of patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2015;56(5):1261–5.CrossRefPubMed Wei X, Wei Y, Huang F, Jing H, Xie M, Hao X, Feng R. Lymphopenia predicts preclinical relapse in the routine follow-up of patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2015;56(5):1261–5.CrossRefPubMed
22.
Zurück zum Zitat Onodera T, Goseki N, Kosaki G. Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients. Nihon Geka Gakkai Zasshi. 1984;85(9):1001–5.PubMed Onodera T, Goseki N, Kosaki G. Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients. Nihon Geka Gakkai Zasshi. 1984;85(9):1001–5.PubMed
23.
Zurück zum Zitat Chen KL, Liu YH, Li WY, Chen J, Gu YK, Geng QR, Jiang WQ, Huang HQ, Lin TY, Xia ZJ, Cai QQ. The prognostic nutritional index predicts survival for patients with extranodal natural killer/T cell lymphoma, nasal type. Ann Hematol. 2015;94(8):1389–400.CrossRefPubMed Chen KL, Liu YH, Li WY, Chen J, Gu YK, Geng QR, Jiang WQ, Huang HQ, Lin TY, Xia ZJ, Cai QQ. The prognostic nutritional index predicts survival for patients with extranodal natural killer/T cell lymphoma, nasal type. Ann Hematol. 2015;94(8):1389–400.CrossRefPubMed
24.
Zurück zum Zitat The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993; 329(14): 987–94.CrossRef The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993; 329(14): 987–94.CrossRef
25.
Zurück zum Zitat Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Muller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275–82.CrossRefPubMed Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Muller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275–82.CrossRefPubMed
26.
Zurück zum Zitat Perkins NJ, Schisterman EF. The inconsistency of “optimal” cutpoints obtained using two criteria based on the receiver operating characteristic curve. Am J Epidemiol. 2006;163(7):670–5.CrossRefPubMedPubMedCentral Perkins NJ, Schisterman EF. The inconsistency of “optimal” cutpoints obtained using two criteria based on the receiver operating characteristic curve. Am J Epidemiol. 2006;163(7):670–5.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Gupta D, Lis CG. Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J. 2010;9:69.CrossRefPubMedPubMedCentral Gupta D, Lis CG. Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J. 2010;9:69.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Brenner DA, Buck M, Feitelberg SP, Chojkier M. Tumor necrosis factor-alpha inhibits albumin gene expression in a murine model of cachexia. J Clin Invest. 1990;85(1):248–55.CrossRefPubMedPubMedCentral Brenner DA, Buck M, Feitelberg SP, Chojkier M. Tumor necrosis factor-alpha inhibits albumin gene expression in a murine model of cachexia. J Clin Invest. 1990;85(1):248–55.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, Delaney A, Jones SJ, Iqbal J, Weisenburger DD, Bast MA, Rosenwald A, Muller-Hermelink HK, Rimsza LM, Campo E, Delabie J, Braziel RM, Cook JR, Tubbs RR, Jaffe ES, Lenz G, Connors JM, Staudt LM, Chan WC, Gascoyne RD. Tumor-associated macrophages and survival in classic Hodgkin’s lymphoma. N Engl J Med. 2010;362(10):875–85.CrossRefPubMedPubMedCentral Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, Delaney A, Jones SJ, Iqbal J, Weisenburger DD, Bast MA, Rosenwald A, Muller-Hermelink HK, Rimsza LM, Campo E, Delabie J, Braziel RM, Cook JR, Tubbs RR, Jaffe ES, Lenz G, Connors JM, Staudt LM, Chan WC, Gascoyne RD. Tumor-associated macrophages and survival in classic Hodgkin’s lymphoma. N Engl J Med. 2010;362(10):875–85.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, Xu W, Tan B, Goldschmidt N, Iqbal J, Vose J, Bast M, Fu K, Weisenburger DD, Greiner TC, Armitage JO, Kyle A, May L, Gascoyne RD, Connors JM, Troen G, Holte H, Kvaloy S, Dierickx D, Verhoef G, Delabie J, Smeland EB, Jares P, Martinez A, Lopez-Guillermo A, Montserrat E, Campo E, Braziel RM, Miller TP, Rimsza LM, Cook JR, Pohlman B, Sweetenham J, Tubbs RR, Fisher RI, Hartmann E, Rosenwald A, Ott G, Muller-Hermelink HK, Wrench D, Lister TA, Jaffe ES, Wilson WH, Chan WC, Staudt LM. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med. 2008;359(22):2313–23.CrossRefPubMed Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, Xu W, Tan B, Goldschmidt N, Iqbal J, Vose J, Bast M, Fu K, Weisenburger DD, Greiner TC, Armitage JO, Kyle A, May L, Gascoyne RD, Connors JM, Troen G, Holte H, Kvaloy S, Dierickx D, Verhoef G, Delabie J, Smeland EB, Jares P, Martinez A, Lopez-Guillermo A, Montserrat E, Campo E, Braziel RM, Miller TP, Rimsza LM, Cook JR, Pohlman B, Sweetenham J, Tubbs RR, Fisher RI, Hartmann E, Rosenwald A, Ott G, Muller-Hermelink HK, Wrench D, Lister TA, Jaffe ES, Wilson WH, Chan WC, Staudt LM. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med. 2008;359(22):2313–23.CrossRefPubMed
Metadaten
Titel
Low prognostic nutritional index predicts poor outcome in diffuse large B-cell lymphoma treated with R-CHOP
verfasst von
Qinjun Zhou
Yongqiang Wei
Fen Huang
Xiaolei Wei
Qi Wei
Xiaoxiao Hao
Yuankun Zhang
Ru Feng
Publikationsdatum
08.07.2016
Verlag
Springer Japan
Erschienen in
International Journal of Hematology / Ausgabe 4/2016
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-016-2052-9

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