Abstract
The World Health Organization (WHO) classification defines diffuse large B-cell lymphoma (DLBCL) as a group of proliferations of large B-cell lymphoid cells with a diffuse growth pattern. It contains some specific entities and a large group of heterogeneous “not otherwise specified” diseases comprising morphologic variants and immunohistochemical, genetic, and molecular subgroups. DLBCL is the most common hematopoietic malignancy, accounting for one-third of mature B-cell neoplasms. Major advances have been observed in the knowledge and the management of DLBCL in the recent years. If the International Prognosis Index (IPI) is still the primary clinical tool used to predict outcome for patients with DLBCL and to guide therapeutic strategies, gene expression profiling and its related biomarkers delineate at least two major histologically indistinguishable molecular subtypes, the germinal center B-cell-like (GCB) subtype and the activated B-cell-like (ABC) subtype, that differ in cure rates and in responsiveness to targeted therapies, independently of the clinical variables. Functional imaging with fluorine-18 deoxyglucose (FDG) positron emission tomography (PET) has become an indispensable mean of assessing the extent of the disease and treatment response. The advent of rituximab has opened the era of targeted therapies in DLBCL and has markedly modified, in combination with chemotherapy, the outcomes in all DLBCL subgroups.
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References
Stein H, Chan JKC, Warnke RA, et al. Diffuse large B-cell lymphoma not otherwise specified. In: Swerdlow SH, Campo E, Harris NL, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2008. p. 233–7.
Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood. 2006;107:265–76.
Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.
d’Amore F, Brincker H, Christensen BE, et al. Non-Hodgkin’s lymphoma in the elderly. A study of 602 patients aged 70 or older from a Danish population-based registry. The Danish LYEO-Study Group. Ann Oncol. 1992;3:379–86.
Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–42.
Pfreundschuh M, Trumper L, Osterborg A, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7:379–91.
Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol (Off J Am Soc Clin Oncol). 2007;25:579–86.
Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403:503–11.
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;346:1937–47.
Shipp MA, Ross KN, Tamayo P, et al. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med. 2002;8:68–74.
Lenz G, Wright G, Dave SS, et al. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med. 2008;359:2313–23.
Conlan MG, Bast M, Armitage JO, Weisenburger DD. Bone marrow involvement by non-Hodgkin’s lymphoma: the clinical significance of morphologic discordance between the lymph node and bone marrow. Nebraska Lymphoma Study Group. J Clin Oncol. 1990;8:1163–72.
Chung R, Lai R, Wei P, et al. Concordant but not discordant bone marrow involvement in diffuse large B-cell lymphoma predicts a poor clinical outcome independent of the International Prognostic Index. Blood. 2007;110:1278–82.
de Kerviler E, de Bazelaire C, Mounier N, et al. Image-guided core-needle biopsy of peripheral lymph nodes allows the diagnosis of lymphomas. Eur Radiol. 2007;17:843–9.
Arber DA, George TI. Bone marrow biopsy involvement by non-Hodgkin’s lymphoma: frequency of lymphoma types, patterns, blood involvement, and discordance with other sites in 450 specimens. Am J Surg Pathol. 2005;29:1549–57.
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 (Off J Am Soc Clin Oncol). 1999;17:1244.
Haioun C, Besson C, Lepage E, et al. Incidence and risk factors of central nervous system relapse in histologically aggressive non-Hodgkin’s lymphoma uniformly treated and receiving intrathecal central nervous system prophylaxis: a GELA study on 974 patients. Groupe d’Etudes des Lymphomes de l’Adulte. Ann Oncol. 2000;11:685–90.
Feugier P, Virion JM, Tilly H, et al. Incidence and risk factors for central nervous system occurrence in elderly patients with diffuse large-B-cell lymphoma: influence of rituximab. Ann Oncol (Off J Eur Soc Medl Oncol/ESMO). 2004;15:129–33.
Boehme V, Schmitz N, Zeynalova S, Loeffler M, Pfreundschuh M. CNS events in elderly patients with aggressive lymphoma treated with modern chemotherapy (CHOP-14) with or without rituximab: an analysis of patients treated in the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Blood. 2009;113:3896–902.
Villa D, Connors JM, Shenkier TN, Gascoyne RD, Sehn LH, Savage KJ. Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: the impact of the addition of rituximab to CHOP chemotherapy. Ann Oncol. 2010;21:1046–52.
Chihara D, Oki Y, Matsuo K, et al. Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: analyses with competing risk regression model. Leuk Lymphoma. 2011;52(12):2270–5.
Hegde U, Filie A, Little RF, et al. High incidence of occult leptomeningeal disease detected by flow cytometry in newly diagnosed aggressive B-cell lymphomas at risk for central nervous system involvement: the role of flow cytometry versus cytology. Blood. 2005;105:496–502.
Quijano S, Lopez A, Manuel Sancho J, et al. Identification of leptomeningeal disease in aggressive B-cell non-Hodgkin’s lymphoma: improved sensitivity of flow cytometry. J Clin Oncol. 2009;27:1462–9.
Sancho JM, Orfao A, Quijano S, et al. Clinical significance of occult cerebrospinal fluid involvement assessed by flow cytometry in non-Hodgkin’s lymphoma patients at high risk of central nervous system disease in the rituximab era. Eur J Haematol. 2010;85:321–8.
Rosenberg SA. Validity of the Ann Arbor staging classification for the non-Hodgkin’s lymphomas. Cancer Treat Rep. 1977;61:1023–7.
Cheson BD. Role of functional imaging in the management of lymphoma. J Clin Oncol (Off J Am Soc Clin Oncol). 2011;29:1844–54.
Ouvrier MJ, Diologent B, Edet-Sanson A, et al. Influence of PET/CT on radiologists and contrast-enhanced CT on nuclear medicine physicians in patients with lymphoma. Q J Nucl Med Mol Imaging. 2011;55:324–33.
Chen YK, Yeh CL, Tsui CC, Liang JA, Chen JH, Kao CH. F-18 FDG PET for evaluation of bone marrow involvement in non-Hodgkin lymphoma: a meta-analysis. Clin Nucl Med. 2011;36:553–9.
Sehn LH, Scott DW, Chhanabhai M, et al. Impact of concordant and discordant bone marrow involvement on outcome in diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol (Off J Am Soc Clin Oncol). 2011;29:1452–7.
Herrmann K, Buck AK, Schuster T, et al. Predictive value of initial 18F-FLT uptake in patients with aggressive non-Hodgkin lymphoma receiving R-CHOP treatment. J Nucl Med (Off Publ Soc Nucl Med). 2011;52:690–6.
Lanic H, Mareschal S, Mechken F, et al. Interim positron emission tomography scan associated with international prognostic index and germinal center B cell-like signature as prognostic index in diffuse large B-cell lymphoma. Leuk Lymphoma. 2011;53(1):34–42.
Phan J, Mazloom A, Jeffrey Medeiros L, et al. Benefit of consolidative radiation therapy in patients with diffuse large B-cell lymphoma treated with R-CHOP chemotherapy. J Clin Oncol (Off J Am Soc Clin Oncol). 2010;28:4170–6.
Chihara D, Oki Y, Onoda H, et al. High maximum standard uptake value (SUVmax) on PET scan is associated with shorter survival in patients with diffuse large B cell lymphoma. Int J Hematol. 2011;93:502–8.
Meignan M, Itti E, Gallamini A, Haioun C. Interim 18 F-fluorodeoxyglucose positron emission tomography in diffuse large B-cell lymphoma: qualitative or quantitative interpretation—where do we stand? Leuk Lymphoma. 2009;50:1753–6.
Lin C, Itti E, Haioun C, et al. Early 18F-FDG PET for prediction of prognosis in patients with diffuse large B-cell lymphoma: SUV-based assessment versus visual analysis. J Nucl Med (Off Publ Soc Nucl Med). 2007;48:1626–32.
Haioun C, Itti E, Rahmouni A, et al. [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in aggressive lymphoma: an early prognostic tool for predicting patient outcome. Blood. 2005;106:1376–81.
Spaepen K, Stroobants S, Dupont P, et al. Early restaging positron emission tomography with (18)F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin’s lymphoma. Ann Oncol (Off J Eur Soc Med Oncol/ESMO). 2002;13:1356–63.
Meignan M, Gallamini A, Haioun C. Report on the first international workshop on interim-PET-scan in lymphoma. Leuk Lymphoma. 2009;50:1257–60.
Casasnovas RO, Meignan M, Berriolo-Riedinger A, et al. SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma. Blood. 2011;118(1):37–43.
Safar V, Dupuis J, Itti E, Jardin F, Fruchart C, Bardet S, Véra P, Copie-Bergman C, Rahmouni A, Tilly H, Meignan M, Haioun C. Interim [18F]fluorodeoxyglucose positron emission tomography scan in diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy plus rituximab. J Clin Oncol. 2012;30:184–90.
Spaepen K, Stroobants S, Dupont P, et al. Prognostic value of pretransplantation positron emission tomography using fluorine 18-fluorodeoxyglucose in patients with aggressive lymphoma treated with high-dose chemotherapy and stem cell transplantation. Blood. 2003;102:53–9.
Cremerius U, Fabry U, Wildberger JE, et al. Pre-transplant positron emission tomography (PET) using fluorine-18-fluoro-deoxyglucose (FDG) predicts outcome in patients treated with high-dose chemotherapy and autologous stem cell transplantation for non-Hodgkin’s lymphoma. Bone Marrow Transplant. 2002;30:103–11.
Schot BW, Pruim J, van Imhoff GW, Sluiter WJ, Vaalburg W, Vellenga E. The role of serial pre-transplantation positron emission tomography in predicting progressive disease in relapsed lymphoma. Haematologica. 2006;91:490–5.
Schot BW, Zijlstra JM, Sluiter WJ, et al. Early FDG-PET assessment in combination with clinical risk scores determines prognosis in recurring lymphoma. Blood. 2007;109:486–91.
Salles G, de Jong D, Xie W, et al. Prognostic significance of immunohistochemical biomarkers in diffuse large B-cell lymphoma: a study from the Lunenburg Lymphoma Biomarker Consortium. Blood. 2011;117:7070–8.
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;109:1857–61.
Bari A, Marcheselli L, Sacchi S, et al. Prognostic models for diffuse large B-cell lymphoma in the rituximab era: a never-ending story. Ann Oncol (Off J Eur Soc Med Oncol/ESMO). 2010;21:1486–91.
Ziepert M, Hasenclever D, Kuhnt E, et al. Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era. J Clin Oncol (Off J Am Soc Clin Oncol). 2010;28:2373–80.
Pfreundschuh M, Kuhnt E, Trumper L, et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011;12:1013–22.
Giachelia M, Voso MT, Tisi MC, et al. Interleukin-6 plasma levels are modulated by a polymorphism in the NF-kB1 gene and are associated with outcome following rituximab-combined chemotherapy in diffuse large B-cell non-Hodgkin lymphoma. Leuk Lymphoma. 2011;53(3):411–6.
Habermann TM, Wang SS, Maurer MJ, et al. Host immune gene polymorphisms in combination with clinical and demographic factors predict late survival in diffuse large B-cell lymphoma patients in the pre-rituximab era. Blood. 2008;112:2694–702.
Rossi D, Rasi S, Franceschetti S, et al. Analysis of the host pharmacogenetic background for prediction of outcome and toxicity in diffuse large B-cell lymphoma treated with R-CHOP21. Leuk (Off J Leuk Soc Am Leuk Res Fund UK). 2009;23:1118–26.
Kim DH, Jung HD, Kim JG, et al. FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma. Blood. 2006;108:2720–5.
Ahlgrimm M, Pfreundschuh M, Kreuz M, Regitz E, Preuss KD, Bittenbring J. Impact of Fc-gamma receptor polymorphisms in elderly patients with diffuse large B-cell lymphoma treated with CHOP with or without rituximab. Blood. 2011;118(17):4657–62.
Oki Y, Yamamoto K, Kato H, et al. Low absolute lymphocyte count is a poor prognostic marker in patients with diffuse large B-cell lymphoma and suggests patients’ survival benefit from rituximab. Eur J Haematol. 2008;81:448–53.
Plonquet A, Haioun C, Jais JP, et al. Peripheral blood natural killer cell count is associated with clinical outcome in patients with aaIPI 2–3 diffuse large B-cell lymphoma. Ann Oncol (Off J Eur Soc Med Oncol/ESMO). 2007;18:1209–15.
Wang F, Xu RH, Luo HY, et al. Clinical and prognostic analysis of hepatitis B virus infection in diffuse large B-cell lymphoma. BMC Cancer. 2008;8:115.
Besson C, Canioni D, Lepage E, et al. Characteristics and outcome of diffuse large B-cell lymphoma in hepatitis C virus-positive patients in LNH 93 and LNH 98 Groupe d’Etude des Lymphomes de l’Adulte programs. J Clin Oncol (Off J Am Soc Clin Oncol). 2006;24:953–60.
Morales D, Beltran B, De Mendoza FH, et al. Epstein-Barr virus as a prognostic factor in de novo nodal diffuse large B-cell lymphoma. Leuk Lymphoma. 2010;51:66–72.
Carbone A, Cesarman E, Spina M, Gloghini A, Schulz TF. HIV-associated lymphomas and gamma-herpesviruses. Blood. 2009;113:1213–24.
Park S, Lee J, Ko YH, et al. The impact of Epstein-Barr virus status on clinical outcome in diffuse large B-cell lymphoma. Blood. 2007;110:972–8.
Riihijarvi S, Koivula S, Nyman H, Rydstrom K, Jerkeman M, Leppa S. Prognostic impact of protein kinase C beta II expression in R-CHOP-treated diffuse large B-cell lymphoma patients. Mod Pathol (Off J US Can Acad Pathol Inc). 2010;23:686–93.
Adida C, Haioun C, Gaulard P, et al. Prognostic significance of survivin expression in diffuse large B-cell lymphomas. Blood. 2000;96:1921–5.
Fridberg M, Servin A, Anagnostaki L, et al. Protein expression and cellular localization in two prognostic subgroups of diffuse large B-cell lymphoma: higher expression of ZAP70 and PKC-beta II in the non-germinal center group and poor survival in patients deficient in nuclear PTEN. Leuk Lymphoma. 2007;48:2221–32.
Iqbal J, Meyer PN, Smith L, et al. BCL2 predicts survival in Germinal center B-cell-like diffuse large B-cell lymphoma treated with CHOP-like therapy and rituximab. Clin Cancer Res (Off J Am Assoc Cancer Res). 2011;17(24):7785–95.
Choi WW, Weisenburger DD, Greiner TC, et al. A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res (Off J Am Assoc Cancer Res). 2009;15:5494–502.
Meyer PN, Fu K, Greiner TC, et al. Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with rituximab. J Clin Oncol (Off J Am Soc Clin Oncol). 2011;29:200–7.
Young KH, Leroy K, Moller MB, et al. Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study. Blood. 2008;112:3088–98.
Iqbal J, Neppalli VT, Wright G, et al. BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma. J Clin Oncol (Off J Am Soc Clin Oncol). 2006;24:961–8.
Lossos IS. Diffuse large B cell lymphoma: from gene expression profiling to prediction of outcome. Biol Blood Marrow Transplant (J Am Soc Blood Marrow Transplant). 2008;14:108–11.
Lenz G, Wright GW, Emre NC, et al. Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci U S A. 2008;105:13520–5.
Barrans S, Crouch S, Smith A, et al. Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma treated in the era of rituximab. J Clin Oncol (Off J Am Soc Clin Oncol). 2010;28:3360–5.
Jardin F, Ruminy P, Kerckaert JP, et al. Detection of somatic quantitative genetic alterations by multiplex polymerase chain reaction for the prediction of outcome in diffuse large B-cell lymphomas. Haematologica. 2008;93:543–50.
Jardin F, Jais JP, Molina TJ, et al. Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study. Blood. 2010;116:1092–104.
Culpin RE, Proctor SJ, Angus B, Crosier S, Anderson JJ, Mainou-Fowler T. A 9 series microRNA signature differentiates between germinal centre and activated B-cell-like diffuse large B-cell lymphoma cell lines. Int J Oncol. 2010;37:367–76.
Lawrie CH, Soneji S, Marafioti T, et al. MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma. Int J Cancer J Int Cancer. 2007;121:1156–61.
Montes-Moreno S, Martinez N, Sanchez-Espiridion B, et al. miRNA expression in diffuse large B-cell lymphoma treated with chemoimmunotherapy. Blood. 2011;118:1034–40.
Alencar AJ, Malumbres R, Kozloski GA, et al. MicroRNAs are independent predictors of outcome in diffuse large B-cell lymphoma patients treated with R-CHOP. Clin Cancer Res (Off J Am Assoc Cancer Res). 2011;17:4125–35.
Lenz G, Staudt LM. Aggressive lymphomas. N Engl J Med. 2010;362:1417–29.
Rayman N, Lam KH, van der Holt B, et al. Prognostic relevance of immunohistochemical subclassification of diffuse large B-cell lymphoma in two prospective phase III clinical trials. Clin Lymphoma Myeloma Leuk. 2011;11:23–32.
Hans CP, Weisenburger DD, Greiner TC, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103:275–82.
Nyman H, Adde M, Karjalainen-Lindsberg ML, et al. Prognostic impact of immunohistochemically defined germinal center phenotype in diffuse large B-cell lymphoma patients treated with immunochemotherapy. Blood. 2007;109:4930–5.
Muris JJ, Meijer CJ, Vos W, et al. Immunohistochemical profiling based on Bcl-2, CD10 and MUM1 expression improves risk stratification in patients with primary nodal diffuse large B cell lymphoma. J Pathol. 2006;208:714–23.
Natkunam Y, Farinha P, Hsi ED, et al. LMO2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy with and without rituximab. J Clin Oncol (Off J Am Soc Clin Oncol). 2008;26:447–54.
Lossos IS, Alizadeh AA, Rajapaksa R, Tibshirani R, Levy R. HGAL is a novel interleukin-4-inducible gene that strongly predicts survival in diffuse large B-cell lymphoma. Blood. 2003;101:433–40.
Lossos IS, Czerwinski DK, Alizadeh AA, et al. Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N Engl J Med. 2004;350:1828–37.
Wright G, Tan B, Rosenwald A, Hurt EH, Wiestner A, Staudt LM. A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc Natl Acad Sci U S A. 2003;100:9991–6.
Rimsza LM, Wright G, Schwartz M, et al. Accurate classification of diffuse large B-cell lymphoma into germinal center and activated B-cell subtypes using a nuclease protection assay on formalin-fixed, paraffin-embedded tissues. Clin Cancer Res (Off J Am Assoc Cancer Res). 2011;17:3727–32.
Alizadeh AA, Gentles AJ, Alencar AJ, et al. Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment. Blood. 2011;118:1350–8.
Copie-Bergman C, Gaulard P, Leroy K, et al. Immuno-fluorescence in situ hybridization index predicts survival in patients with diffuse large B-cell lymphoma treated with R-CHOP: a GELA study. J Clin Oncol (Off J Am Soc Clin Oncol). 2009;27:5573–9.
Meyer PN, Fu K, Greiner T, et al. The stromal cell marker SPARC predicts for survival in patients with diffuse large B-cell lymphoma treated with rituximab. Am J Clin Pathol. 2011;135:54–61.
Gratzinger D, Zhao S, Tibshirani RJ, et al. Prognostic significance of VEGF, VEGF receptors, and microvessel density in diffuse large B cell lymphoma treated with anthracycline-based chemotherapy. Lab Investig (J Tech Methods Pathol). 2008;88:38–47.
Evens AM, Sehn LH, Farinha P, et al. Hypoxia-inducible factor-1a expression predicts superior survival in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol (Off J Am Soc Clin Oncol). 2010;28:1017–24.
Sakata K, Satoh M, Someya M, et al. Expression of matrix metalloproteinase 9 is a prognostic factor in patients with non-Hodgkin lymphoma. Cancer. 2004;100:356–65.
Wang L, Liu P, Chen X, Geng Q, Lu Y. Serum neuron-specific enolase is correlated with clinical outcome of patients with non-germinal center B cell-like subtype of diffuse large B-cell lymphoma treated with rituximab-based immunochemotherapy. Med Oncol. 2011;29(3):2153–8.
Maurer MJ, Micallef IN, Cerhan JR, et al. Elevated serum free light chains are associated with event-free and overall survival in two independent cohorts of patients with diffuse large B-cell lymphoma. J Clin Oncol (Off J Am Soc Clin Oncol). 2011;29:1620–6.
Drake MT, Maurer MJ, Link BK, et al. Vitamin D insufficiency and prognosis in non-Hodgkin’s lymphoma. J Clin Oncol (Off J Am Soc Clin Oncol). 2010;28:4191–8.
Last KW, Cornelius V, Delves T, et al. Presentation serum selenium predicts for overall survival, dose delivery, and first treatment response in aggressive non-Hodgkin’s lymphoma. J Clin Oncol (Off J Am Soc Clin Oncol). 2003;21:2335–41.
Lawrie CH, Gal S, Dunlop HM, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141:672–5.
Lech-Maranda E, Bienvenu J, Michallet AS, et al. Elevated IL-10 plasma levels correlate with poor prognosis in diffuse large B-cell lymphoma. Eur Cytokine Netw. 2006;17:60–6.
Lopez-Guillermo A, Colomo L, Jimenez M, et al. Diffuse large B-cell lymphoma: clinical and biological characterization and outcome according to the nodal or extranodal primary origin. J Clin Oncol (Off J Am Soc Clin Oncol). 2005;23:2797–804.
Niitsu N, Okamoto M, Okabe-Kado J, et al. Serum nm23-H1 protein as a prognostic factor for indolent non-Hodgkin’s lymphoma. Leuk (Off J Leuk Soc Am Leuk Res Fund UK). 2001;15:832–9.
Goto N, Tsurumi H, Kasahara S, et al. Serum interleukin-18 level is associated with the outcome of patients with diffuse large B-cell lymphoma treated with CHOP or R-CHOP regimens. Eur J Haematol. 2011;87:217–27.
Bono P, Teerenhovi L, Joensuu H. Elevated serum endostatin is associated with poor outcome in patients with non-Hodgkin lymphoma. Cancer. 2003;97:2767–75.
Molina A. A decade of rituximab: improving survival outcomes in non-Hodgkin’s lymphoma. Annu Rev Med. 2008;59:237–50.
Armitage JO, Cheson BD. Interpretation of clinical trials in diffuse large-cell lymphoma. J Clin Oncol. 1988;6:1335–47.
A predictive model for aggressive non-Hodgkin’s lymphoma. The international Non-Hodgkin’s lymphoma prognostic factors project. N Engl J Med. 1993;329:987–94.
Tilly H, Dreyling M. Diffuse large B-cell non-Hodgkin’s lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 Suppl 5Suppl 5:v172–4.
Miller TP, Dahlberg S, Cassady JR, et al. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin’s lymphoma. N Engl J Med. 1998;339:21–6.
Bonnet C, Fillet G, Mounier N, et al. CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol. 2007;25:787–92.
Reyes F, Lepage E, Ganem G, et al. ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med. 2005;352:1197–205.
Pfreundschuh M, Trumper L, Kloess M, et al. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004;104:626–33.
Ketterer N, Coiffier B, Thieblemont C, et al. ACVBP versus ACVBP plus rituximab for young patients with localized low-risk diffuse large B-cell lymphoma. In: International conference on malignant lymphoma, Ann Oncol, Lugano; 2011. p. 91.
Persky DO, Unger JM, Spier CM, et al. Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol (Off J Am Soc Clin Oncol). 2008;26:2258–63.
Recher C, Coiffier B, Haioun C, et al. Randomized phase 3 study (LNH03–2B) of intensified chemotherapy ACVBP plus rituximab versus standard CHOP plus rituximab for young patients with diffuse large B-cell lymphoma. 2011;378(9806):1858–67.
Gianni AM, Bregni M, Siena S, et al. High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med. 1997;336:1290–7.
Haioun C, Lepage E, Gisselbrecht C, et al. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin’s lymphoma: final analysis of the prospective LNH87–2 protocol—a groupe d’Etude des lymphomes de l’Adulte study. J Clin Oncol. 2000;18:3025–30.
Santini G, Salvagno L, Leoni P, et al. VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin’s lymphoma: results of a prospective randomized trial by the non-Hodgkin’s Lymphoma Cooperative Study Group. J Clin Oncol. 1998;16:2796–802.
Gisselbrecht C, Lepage E, Molina T, et al. Shortened first-line high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma. J Clin Oncol. 2002;20:2472–9.
Milpied N, Deconinck E, Gaillard F, et al. Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. N Engl J Med. 2004;350:1287–95.
Greb A, Bohlius J, Trelle S, et al. High-dose chemotherapy with autologous stem cell support in first-line treatment of aggressive non-Hodgkin lymphoma—results of a comprehensive meta-analysis. Cancer Treat Rev. 2007;33:338–46.
Stiff PJ, Unger JM, Cook J, et al. Randomized phase III U.S./Canadian intergroup trial (SWOG S9704) comparing CHOP ± R for eight cycles to CHOP ± R for six cycles followed by autotransplant for patients with high-intermediate (H-Int) or high IPI grade diffuse aggressive non-Hodgkin lymphoma (NHL). J Clin Oncol. 2011;29. Abstract 8001.
Tarella C, Zanni M, Di Nicola M, et al. Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi). Leukemia. 2007;21:1802–11.
Glass B, Ziepert M, Reiser M, et al. High-dose therapy followed by autologous stem-cell transplantation with and without rituximab for primary treatment of high-risk diffuse large B-cell lymphoma. Ann Oncol (Off J Eur Soc Med Oncol/ESMO). 2010;21:2255–61.
Vitolo U, Chiappella A, Angelucci E, et al. Dose-dense and high-dose chemotherapy plus rituximab with autologous stem cell transplantation for primary treatment of diffuse large B-cell lymphoma with a poor prognosis: a phase II multicenter study. Haematologica. 2009;94:1250–8.
Fitoussi O, Belhadj K, Mounier N, et al. Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA. Haematologica. 2011;96:1136–43.
Schmitz N, Nickelsen M, Ziepert M, et al. Conventional chemoimmunotherapy (R-CHOEP-14) or high-dose therapy (R-Mega-CHOEP) for young, high-risk patients with aggressive B-cell lymphoma: final results of the randomized Mega-CHOEP trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). J Clin Oncol. 2012;13(12):1250–9.
Casasnovas RO, Meignan M, Berriolo-Riedinger A, et al. SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma. Blood. 2011;118:37–43.
Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010;116(12):2040–5.
Habermann TM, Weller EA, Morrison VA, et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24:3121–7.
Tilly H, Lepage E, Coiffier B, et al. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003;102:4284–9.
Pfreundschuh M, Trumper L, Kloess M, et al. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004;104:634–41.
Pfreundschuh M, Schubert J, Ziepert M, et al. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008;9:105–16.
Delarue R, Tilly H, Salles A, et al. R-CHOP14 compared to R-CHOP21 in elderly patients with diffuse large B-cell lymphoma: results of the interim analysis of the LNH03–6B GELA study. Blood. 2009;114. Abstract 406.
Cunningham D, Smith P, Mouncey P, et al. R-CHOP14 versus R-CHOP21: result of a randomized phase III trial for the treatment of patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma. J Clin Oncol. 2011;29. Abstract 8000.
Ferreri AJ, Assanelli A, Crocchiolo R, Ciceri F. Central nervous system dissemination in immunocompetent patients with aggressive lymphomas: incidence, risk factors and therapeutic options. Hematol Oncol. 2009;27:61–70.
Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin’s lymphoma: a 20-year follow-up analysis of SWOG 8516—the Southwest Oncology Group. J Clin Oncol. 2009;27:114–9.
Kridel R, Dietrich PY. Prevention of CNS relapse in diffuse large B-cell lymphoma. Lancet Oncol. 2011;12(13):1258–66.
Abramson JS, Hochberg EP. Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high-risk patients with diffuse large B-cell lymphoma. Cancer. 2010;116(18):4283–90.
Yamamoto W, Tomita N, Watanabe R, et al. Central nervous system involvement in diffuse large B-cell lymphoma. Eur J Haematol. 2010;85:6–10.
Tai WM, Chung J, Tang PL, et al. Central nervous system (CNS) relapse in diffuse large B cell lymphoma (DLBCL): pre- and post-rituximab. Ann Hematol. 2011;90:809–18.
Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med. 1995;333:1540–5.
Velasquez WS, Cabanillas F, Salvador P, et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988;71:117–22.
Cabanillas F, Velasquez WS, McLaughlin P, et al. Results of recent salvage chemotherapy regimens for lymphoma and Hodgkin’s disease. Semin Hematol. 1988;25:47–50.
Stamatoullas A, Fruchart C, Bastit D, et al. Ifosfamide, etoposide, cytarabine, and methotrexate as salvage chemotherapy in relapsed or refractory aggressive non-Hodgkin’s lymphoma. Cancer. 1996;77:2302–7.
Moskowitz CH, Bertino JR, Glassman JR, et al. Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin’s lymphoma. J Clin Oncol. 1999;17:3776–85.
Gisselbrecht C, Mounier N. Rituximab: enhancing outcome of autologous stem cell transplantation in non-Hodgkin’s lymphoma. Semin Oncol. 2003;30:28–33.
Vellenga E, van Putten WL, van’t Veer MB, et al. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008;111:537–43.
Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184–90.
Thieblemont C, Briere J, Mounier N, et al. The Germinal center/activated B-cell subclassification has a prognostic impact for response to salvage therapy in relapsed/refractory diffuse large B-cell lymphoma: a bio-CORAL study. J Clin Oncol. 2011;29(31):4079–87.
Gisselbrecht C, Glass B, Laurent G, et al. Maintenance with rituximab after autologous stem cell transplantation in relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL): CORAL final analysis. J Clin Oncol. 2011;29:8004.
El Gnaoui T, Dupuis J, Belhadj K, et al. Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy. Ann Oncol (Off J Eur Soc Med Oncol/ESMO). 2007;18:1363–8.
Corazzelli G, Russo F, Capobianco G, Marcacci G, Della Cioppa P, Pinto A. Gemcitabine, ifosfamide, oxaliplatin and rituximab (R-GIFOX), a new effective cytoreductive/mobilizing salvage regimen for relapsed and refractory aggressive non-Hodgkin’s lymphoma: results of a pilot study. Ann Oncol (Off J Eur Soc Med Oncol/ESMO). 2006;17 Suppl 4Suppl 4:iv18–24.
Gisselbrecht C. Use of rituximab in diffuse large B-cell lymphoma in the salvage setting. Br J Haematol. 2008;143:607–21.
van Kampen RJ, Canals C, Schouten HC, et al. Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell non-Hodgkin’s lymphoma relapsing after an autologous stem-cell transplantation: an analysis of the European Group for Blood and Marrow Transplantation Registry. J Clin Oncol. 2011;29:1342–8.
Friedberg JW. New strategies in diffuse large B-cell lymphoma: translating findings from gene expression analyses into clinical practice. Clin Cancer Res (Off J Am Assoc Cancer Res). 2011;17:6112–7.
Dunleavy K, Wilson WH. Role of molecular subtype in predicting outcome of AIDS-related diffuse large B-cell lymphoma. J Clin Oncol (Off J Am Soc Clin Oncol). 2010;28:e260. Author reply e1–2.
Ruan J, Martin P, Furman RR, et al. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol (Off J Am Soc Clin Oncol). 2011;29:690–7.
Furman RR, Martin P, Ruan J, et al. Phase 1 trial of bortezomib plus R-CHOP in previously untreated patients with aggressive non-Hodgkin lymphoma. Cancer. 2010;116:5432–9.
Mozos A, Roue G, Lopez-Guillermo A, et al. The expression of the endoplasmic reticulum stress sensor BiP/GRP78 predicts response to chemotherapy and determines the efficacy of proteasome inhibitors in diffuse large B-cell lymphoma. Am J Pathol. 2011;179(5):2601–10.
Hideshima T, Ikeda H, Chauhan D, et al. Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells. Blood. 2009;114:1046–52.
Dasmahapatra G, Lembersky D, Rahmani M, et al. Bcl-2 antagonists interact synergistically with bortezomib in DLBCL cells in association with JNK activation and induction of ER stress. Cancer Biol Ther. 2009;8:808–19.
Dasmahapatra G, Lembersky D, Kramer L, et al. The pan-HDAC inhibitor vorinostat potentiates the activity of the proteasome inhibitor carfilzomib in human DLBCL cells in vitro and in vivo. Blood. 2010;115:4478–87.
Paoluzzi L, Gonen M, Bhagat G, et al. The BH3-only mimetic ABT-737 synergizes the antineoplastic activity of proteasome inhibitors in lymphoid malignancies. Blood. 2008;112:2906–16.
Ferch U, Kloo B, Gewies A, et al. Inhibition of MALT1 protease activity is selectively toxic for activated B cell-like diffuse large B cell lymphoma cells. J Exp Med. 2009;206:2313–20.
Hernandez-Ilizaliturri FJ, Deeb G, Zinzani PL, et al. Higher response to lenalidomide in relapsed/refractory diffuse large b-cell lymphoma in nongerminal center b-cell-like than in germinal center b-cell-like phenotype. Cancer. 2011;117(22):5058–66.
Leonard JP, Martin P, Barrientos J, Elstrom R. Targeted treatment and new agents in diffuse large B-cell lymphoma. Semin Hematol. 2008;45:S11–6.
Witzig TE, Gupta M. Signal transduction inhibitor therapy for lymphoma. Hematol Educ Program Am Soc Hematol Am Soc Hematol Educ Program. 2010;2010:265–70.
Friedberg JW, Sharman J, Sweetenham J, et al. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood. 2010;115:2578–85.
Honigberg LA, Smith AM, Sirisawad M, et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A. 2010;107:13075–80.
Davis RE, Ngo VN, Lenz G, et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature. 2010;463:88–92.
Robertson MJ, Kahl BS, Vose JM, et al. Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol (Off J Am Soc Clin Oncol). 2007;25:1741–6.
Cerchietti LC, Ghetu AF, Zhu X, et al. A small-molecule inhibitor of BCL6 kills DLBCL cells in vitro and in vivo. Cancer Cell. 2010;17:400–11.
Briones J. Targeted therapy of BCL6-dependent diffuse large B-cell lymphomas by heat-shock protein 90 inhibition. Expert Rev Hematol. 2010;3:157–9.
Cerchietti LC, Hatzi K, Caldas-Lopes E, et al. BCL6 repression of EP300 in human diffuse large B cell lymphoma cells provides a basis for rational combinatorial therapy. J Clin Investig. 2010;pii:42869.
Cerchietti LC, Lopes EC, Yang SN, et al. A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6-dependent B cell lymphomas. Nat Med. 2009;15:1369–76.
Wilson WH, Dunleavy K, Pittaluga S, et al. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol (Off J Am Soc Clin Oncol). 2008;26:2717–24.
Lenz G, Davis RE, Ngo VN, et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science. 2008;319:1676–9.
Cardesa-Salzmann TM, Colomo L, Gutierrez G, et al. High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy. Haematologica. 2011;96:996–1001.
Stopeck AT, Unger JM, Rimsza LM, et al. A phase II trial of single agent bevacizumab in patients with relapsed, aggressive non-Hodgkin lymphoma: southwest oncology group study S0108. Leuk Lymphoma. 2009;50:728–35.
Ganjoo KN, An CS, Robertson MJ, et al. Rituximab, bevacizumab and CHOP (RA-CHOP) in untreated diffuse large B-cell lymphoma: safety, biomarker and pharmacokinetic analysis. Leuk Lymphoma. 2006;47:998–1005.
Beltran BE, Castillo JJ, Morales D, et al. EBV-positive diffuse large B-cell lymphoma of the elderly: a case series from Peru. Am J Hematol. 2011;86:663–7.
Castillo JJ, Beltran BE, Miranda RN, Paydas S, Winer ES, Butera JN. Epstein-barr virus-positive diffuse large B-cell lymphoma of the elderly: what we know so far. Oncologist. 2011;16:87–96.
Hofscheier A, Ponciano A, Bonzheim I, et al. Geographic variation in the prevalence of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly: a comparative analysis of a Mexican and a German population. Mod Pathol (Off J US Can Acad Pathol Inc). 2011;24:1046–54.
Grange F, Beylot-Barry M, Courville P, et al. Primary cutaneous diffuse large B-cell lymphoma, leg type: clinicopathologic features and prognostic analysis in 60 cases. Arch Dermatol. 2007;143:1144–50.
Petitjean B, Jardin F, Joly B, et al. Pyothorax-associated lymphoma: a peculiar clinicopathologic entity derived from B cells at late stage of differentiation and with occasional aberrant dual B- and T-cell phenotype. Am J Surg Pathol. 2002;26:724–32.
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;117:5019–32.
Mareschal S, Lanic H, Ruminy P, Bastard C, Tilly H, Jardin F. The proportion of activated B-cell like subtype among de novo diffuse large B-cell lymphoma increases with age. Haematologica. 2011;96(12):1888–90.
Peyrade F, Jardin F, Thieblemont C, et al. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2011;12:460–8.
Thieblemont C, Coiffier B. Lymphoma in older patients. J Clin Oncol (Off J Am Soc Clin Oncol). 2007;25:1916–23.
Thieblemont C, Grossoeuvre A, Houot R, et al. Non-Hodgkin’s lymphoma in very elderly patients over 80 years. A descriptive analysis of clinical presentation and outcome. Ann Oncol (Off J Eur Soc Med Oncol/ESMO). 2008;19:774–9.
Advani RH, Chen H, Habermann TM, et al. Comparison of conventional prognostic indices in patients older than 60 years with diffuse large B-cell lymphoma treated with R-CHOP in the US Intergroup Study (ECOG 4494, CALGB 9793): consideration of age greater than 70 years in an elderly prognostic index (E-IPI). Br J Haematol. 2010;151:143–51.
Pfreundschuh M. How I, treat elderly patients with diffuse large B-cell lymphoma. Blood. 2010;116:5103–10.
Walter LC, Covinsky KE. Cancer screening in elderly patients: a framework for individualized decision making. J Am Med Assoc. 2001;285:2750–6.
Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol (Off J Am Soc Clin Oncol). 2007;25:1824–31.
Stuck AE, Siu AL, Wieland GD, Adams J, Rubenstein LZ. Comprehensive geriatric assessment: a meta-analysis of controlled trials. Lancet. 1993;342:1032–6.
Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist. 2000;5:224–37.
Tucci A, Ferrari S, Bottelli C, Borlenghi E, Drera M, Rossi G. A comprehensive geriatric assessment is more effective than clinical judgment to identify elderly diffuse large cell lymphoma patients who benefit from aggressive therapy. Cancer. 2009;115:4547–53.
Siegel AB, Lachs M, Coleman M, Leonard JP. Lymphoma in elderly patients: novel functional assessment techniques provide better discrimination among patients than traditional performance status measures. Clin Lymphoma Myeloma. 2006;7:65–9.
Hurria A, Gupta S, Zauderer M, et al. Developing a cancer-specific geriatric assessment: a feasibility study. Cancer. 2005;104:1998–2005.
Luciani A, Ascione G, Bertuzzi C, et al. Detecting disabilities in older patients with cancer: comparison between comprehensive geriatric assessment and vulnerable elders survey-13. J Clin Oncol (Off J Am Soc Clin Oncol). 2010;28:2046–50.
Kobayashi Y, Miura K, Hojo A, et al. Charlson Comorbidity Index is an independent prognostic factor among elderly patients with diffuse large B-cell lymphoma. J Cancer Res Clin Oncol. 2011;137:1079–84.
Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol (Off J Am Soc Clin Oncol). 2011;29:3457–65.
Janssen-Heijnen ML, Extermann M, Boler IE. Can first cycle CBCs predict older patients at very low risk of neutropenia during further chemotherapy? Crit Rev Oncol/Hematol. 2011;79:43–50.
Hasselblom S, Stenson M, Werlenius O, et al. Improved outcome for very elderly patients with diffuse large B-cell lymphoma in the immunochemotherapy era. Leuk Lymphoma. 2011;53(3):394–9.
Musolino A, Boggiani D, Panebianco M, et al. Activity and safety of dose-adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab in very elderly patients with poor-prognostic untreated diffuse large B-cell non-Hodgkin lymphoma. Cancer. 2011;117:964–73.
Meguro A, Ozaki K, Sato K, et al. Rituximab plus 70% cyclophosphamide, doxorubicin, vincristine and prednisone for Japanese patients with diffuse large B-cell lymphoma aged 70 years and older. Leuk Lymphoma. 2011;53(1):43–9.
Visani G, Ferrara F, Alesiani F, et al. R-COMP 21 for frail elderly patients with aggressive B-cell non-Hodgkin lymphoma: a pilot study. Leuk Lymphoma. 2008;49:1081–6.
Corazzelli G, Frigeri F, Arcamone M, et al. Biweekly rituximab, cyclophosphamide, vincristine, non-pegylated liposome-encapsulated doxorubicin and prednisone (R-COMP-14) in elderly patients with poor-risk diffuse large B-cell lymphoma and moderate to high ‘life threat’ impact cardiopathy. Br J Haematol. 2011;154:579–89.
Zinzani PL, Pellegrini C, Gandolfi L, et al. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011;11(6):462–6.
Weidmann E, Neumann A, Fauth F, et al. Phase II study of bendamustine in combination with rituximab as first-line treatment in patients 80 years or older with aggressive B-cell lymphomas. Ann Oncol (Off J Eur Soc Med Oncol/ESMO). 2011;22:1839–44.
Rigacci L, Fabbri A, Puccini B, et al. Oxaliplatin-based chemotherapy (dexamethasone, high-dose cytarabine, and oxaliplatin)+/−rituximab is an effective salvage regimen in patients with relapsed or refractory lymphoma. Cancer. 2010;116:4573–9.
Jantunen E, Canals C, Rambaldi A, et al. Autologous stem cell transplantation in elderly patients (> or =60 years) with diffuse large B-cell lymphoma: an analysis based on data in the European Blood and Marrow Transplantation registry. Haematologica. 2008;93:1837–42.
Aapro MS, Bohlius J, Cameron DA, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47:8–32.
Zwick C, Hartmann F, Zeynalova S, et al. Randomized comparison of pegfilgrastim day 4 versus day 2 for the prevention of chemotherapy-induced leukocytopenia. Ann Oncol (Off J Eur Soc Med Oncol/ESMO). 2011;22:1872–7.
Brunello A, Kapoor R, Extermann M. Hyperglycemia during chemotherapy for hematologic and solid tumors is correlated with increased toxicity. Am J Clin Oncol. 2011;34:292–6.
Lin PC, Hsiao LT, Poh SB, et al. Higher fungal infection rate in elderly patients (more than 80 years old) suffering from diffuse large B cell lymphoma and treated with rituximab plus CHOP. Ann Hematol. 2007;86:95–100.
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Jardin, F., Tilly, H. (2013). Diffuse Large B-Cell Lymphoma. In: Younes, A., Coiffier, B. (eds) Lymphoma. Current Clinical Oncology, vol 43. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-408-1_11
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