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Diffuse Large B-Cell Lymphomas in Older Adults

  • Vicki A. Morrison
Living reference work entry

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in the elderly and is increasing in incidence. Although significant therapeutic advances have recently been made in the care of older DLBCL patients, based upon results of randomized clinical trials, many older patients are not eligible for such trials due to comorbidities and functional decline. Pretreatment evaluation of older patients to ascertain potential tolerance to therapy is especially important in therapeutic decisions for this population. Evaluation by performance status alone is insufficient, especially in the elderly, and consideration of the impact of comorbidities and functional/social decline needs to be included in such assessment. In this chapter, we will review approaches to therapy of the older patients with DLBCL, including initial treatment, role of maintenance therapy, use of combined modality therapy for limited stage disease, and strategies for the relapsed/refractory older patient. We will also address the issues of prognosis, comorbidities, geriatric assessment, supportive care measures in older patients with DLBCL, and recommendations for assessment and allied care.

Keywords

Diffuse large B-cell lymphoma Non-Hodgkin lymphoma Elderly Therapy Prognosis Geriatric assessment 

References

  1. Aaldriks AA, Giltay EL, Nortier JWR, et al. Prognostic significance of geriatric assessment in combination with laboratory parameters in elderly patients with aggressive non-Hodgkin lymphoma. Leuk Lymphoma. 2015;56:927–35.PubMedCrossRefGoogle Scholar
  2. Aapro MS, Cameron DA, Pettengell R, et al. EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours. Eur J Cancer. 2006;42:2433–53.PubMedCrossRefGoogle Scholar
  3. Aapro M, Bernard-Marty C, Brain E, Batist G, Erdkamp F, Krzemieniecki K, et al. Anthracycline cardiotoxicity in the elderly cancer patient: a SIOG expert position paper. Ann Oncol. 2011;22:257–67.PubMedCrossRefGoogle Scholar
  4. Adida C, Haioun C, Gaulard P, Lepage E, Morel P, Briere J, et al. Prognostic significance of survivin expression in diffuse large B-cell lymphoma. Blood. 2000;96:1921–5.PubMedGoogle Scholar
  5. Advani RH, Chen H, Habermann TM, Morrison VA, Weller EA, Fisher RI, 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.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403:503–11.PubMedCrossRefGoogle Scholar
  7. Andorsky DJ, Cohen M, Naeim A, et al. Outcomes of auto-SCT for lymphoma in subjects aged 70 years and over. Bone Marrow Transplant. 2011;46:1219–25.PubMedCrossRefGoogle Scholar
  8. Argyriou AA, Bruna J, Marmiroli P, Cavaletti G. Chemotherapy-induced peripheral neurotoxicity (CIPN): an update. Crit Rev Oncol Hematol. 2012;82:51–77.PubMedCrossRefGoogle Scholar
  9. Armitage JO, Potter JF. Aggressive chemotherapy for diffuse histiocytic lymphoma in the elderly: increased complications with advancing age. J Am Geriatr Soc. 1984;32:269–73.PubMedCrossRefGoogle Scholar
  10. Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol. 1998;16:2780–95.PubMedCrossRefGoogle Scholar
  11. Armitage JO, Carbone PP, Connors JM, et al. Treatment-related myelodysplasia and acute leukemia in non-Hodgkin’s lymphoma patients. J Clin Oncol. 2003;21:897–906.PubMedCrossRefGoogle Scholar
  12. Aviles A, Cleto S, Huerta-Guzman J, Neri N. Interferon alfa 2b as maintenance therapy in poor risk diffuse large B-cell lymphoma in complete remission after intensive CHOP±BLEO regimens. Eur J Haematol. 2001;66:94–9.PubMedCrossRefGoogle Scholar
  13. Avilés A, Neri N, Nambo J, et al. Maintenance therapy with interferon-a 2b, cyclophosphamide, and prednisone in aggressive diffuse large cell lymphoma. Stem Cells Dev. 2004;13:205–9.PubMedCrossRefGoogle Scholar
  14. Balducci L. Aging, frailty, and chemotherapy. Cancer Control. 2007;14:7–12.PubMedCrossRefGoogle Scholar
  15. Balducci L. Supportive care in elderly cancer patients. Curr Opin Oncol. 2009;21:310–7.PubMedCrossRefGoogle Scholar
  16. Balducci L, Beghe C. The application of the principles of geriatrics to the management of the older person with cancer. Crit Rev Oncol Hematol. 2000;35:147–54.PubMedCrossRefGoogle Scholar
  17. Balducci L, Repetto L. Increased risk of myelotoxicity in elderly patients with non-Hodgkin lymphoma. Cancer. 2004;100:6–11.PubMedCrossRefGoogle Scholar
  18. Ballester OF, Moscinski L, Spiers A, Balducci L. Non-Hodgkin's lymphoma in the older person: a review. J Am Geriatr Soc. 1993;41:1245–54.PubMedCrossRefGoogle Scholar
  19. Ballonoff A, Rusthoven KE, Schwer A, et al. Outcomes and effect of radiotherapy in patients with stage I or II diffuse large B-cell lymphoma: a surveillance, epidemiology, and end results analysis. Int J Radiat Oncol Biol Phys. 2008;72:1465–71.PubMedCrossRefGoogle Scholar
  20. Barrans SL, Fenton JA, Banham A, Owen RG, Jack AS. Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome. Blood. 2004;104:2933–5.PubMedCrossRefGoogle Scholar
  21. Bastion Y, Blay JY, Divine M. Elderly patients with aggressive non-Hodgkin’s lymphoma: disease presentation, response to treatment, and survival – a Groupe d’Etude des Lymphomes de l’Adulte study on 453 patients older than 69 years. J Clin Oncol. 1997;15:2945–53.PubMedCrossRefGoogle Scholar
  22. Boehme V, Schmitz N, Zeynalova S, et al. 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.PubMedCrossRefGoogle Scholar
  23. Bonnet C, Fillet G, Mournier 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.PubMedCrossRefGoogle Scholar
  24. Campbell C, Sawka C, Franssen E, Berinstein NL. Delivery of full dose CHOP chemotherapy to elderly patients with aggressive non-Hodgkin’s lymphoma without G-CSF support. Leuk Lymphoma. 1999;35:119–27.PubMedCrossRefGoogle Scholar
  25. Campbell BA, Connors JM, Gascoyne RD, et al. Limited-stage diffuse large B-cell lymphoma treated with abbreviated systemic therapy and consolidation radiotherapy. Cancer. 2012;118:4156–65.PubMedCrossRefGoogle Scholar
  26. Chao NJ, Rosenberg SA, Horning SJ. CEPP(B): an effective and well-tolerated regimen in poor-risk, aggressive non-Hodgkin’s lymphoma. Blood. 1990;76:1293–8.PubMedGoogle Scholar
  27. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.PubMedCrossRefGoogle Scholar
  28. Charlson M, Szatrowski TP, Peterson J, et al. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47:1245–51.PubMedCrossRefGoogle Scholar
  29. Chen MG, Prosnitz LR, Gonzalez-Serva A, et al. Results of radiotherapy in control of stage I and II non-Hodgkin’s lymphoma. Cancer. 1979;43:1245–54.PubMedCrossRefGoogle Scholar
  30. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059–67.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Choi WW, Weisenburger DD, Greiner TC, Piris MA, Banham AH, Delabie J, et al. A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res. 2009;15:5494–502.PubMedCrossRefGoogle Scholar
  32. Chrischilles EA, Klepser DG, Brooks JM, et al. Effect of clinical characteristics on neutropenia-related inpatient costs among newly diagnosed non-Hodgkin’s lymphoma cases during first-course chemotherapy. Pharmacotherapy. 2005;25:668–75.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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;116:2040–5.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Coleman M, Martin P, Ruan J, et al. Prednisone, etoposide, procarbazine, and cyclophosphamide (PEP-C) oral combination chemotherapy regimen for recurring/refractory lymphoma: low-dose metronomic, multidrug therapy. Cancer. 2008;112:2228–32.PubMedCrossRefGoogle Scholar
  36. Colosia A, Njue A, Trask PC, Olivares R, Khan S, Abbe A, Police R, Wang J, Ruiz-Soto R, Kaye JA, Awan F. Clinical eficacy and safety in relapsed/refractory diffuse large B-cell lymphoma: a systematic literature review. Clin Lymphoma Myeloma Leuk. 2014;14:343–55.PubMedCrossRefGoogle Scholar
  37. Connors JM, O’Reilly SE. Treatment considerations in the elderly patient with lymphoma. Hematol Oncol Clin North Am. 1997;11:949–60.PubMedCrossRefGoogle Scholar
  38. Copie-Bergman C, Gaulard P, Leroy K, Briere J, Baia M, Jais JP, 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. 2009;27:5573–9.PubMedCrossRefGoogle Scholar
  39. Corazzelli G, Capobianco G, Arcamone M, et al. Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-ineligible patients with refractory/relapsing B-cell lymphoma. Cancer Chemother Pharmacol. 2009;64:907–16.PubMedCrossRefGoogle Scholar
  40. Corrazelli 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.CrossRefGoogle Scholar
  41. Cunningham D, Hawkes EA, Jack A, et al. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013;381:1817–26.PubMedCrossRefGoogle Scholar
  42. Dahi PB, Tamari R, Devlin SM, Maloy M, Bhatt V, Scordo M, Goldberg J, Zelenetz AD, Hamlin PA, Matsar MJ, Maragulia J, Giralt SA, Perales MA, Moskowitz CH, Sauter CS. Favorable outcomes in elderly patients undergoing high-dose therapy and autologous stem cell transplantation for non-Hodgkin lymphoma. Biol Blood Marrow Transplant. 2014;20:2004–9.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Deeg HJ, Sandmaier BM. Who is fit for allogeneic transplantation? Blood. 2010;116:4762–70.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Delarue R, Tilly H, Mounier N, et al. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013;14:525–33.PubMedCrossRefGoogle Scholar
  45. Dorth JA, Prosnitz LR, Broadwater G, et al. Impact of consolidation radiation therapy in stage III-IV diffuse large B-cell lymphoma with negative post-chemotherapy radiologic imaging. Int J Radiat Oncol Biol Phys. 2012;84:762–7.PubMedCrossRefGoogle Scholar
  46. 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. 2007;18:1363–8.PubMedCrossRefGoogle Scholar
  47. Elstrom RL, Martin P, Ostrow K, et al. Response to second-line therapy defines the potential for cure in patients with recurrent diffuse large B-cell lymphoma: implications for the development of novel therapeutic strategies. Clin Lymphoma Myeloma Leuk. 2010;10:192–6.PubMedCrossRefGoogle Scholar
  48. Elstrom RL, Martin P, Hurtado Rua S, et al. Autologous stem cell transplant is feasible in very elderly patients with lymphoma and limited comorbidity. Am J Hematol. 2012;87:433–5.PubMedCrossRefGoogle Scholar
  49. Eschenhagen T, Force T, Ewer MS, de Keulenaer GW, Suter TM, Anker SD, et al. Cardiovascular side effects of cancer therapies: a position statement from the heart failure Association of the European Society of cardiology. Eur J Heart Fail. 2011;13:1–10.PubMedCrossRefGoogle Scholar
  50. Evens AM, Sehn LH, Farinha P, Nelson BP, Raji A, Lu Y, et al. Hypoxia-inducible factor-1 (alpha) expression predicts superior survival in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2010;28:1017–24.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Extermann M. Older patients, cognitive impairment, and cancer: an increasingly frequent triad. J Natl Compr Cancer Netw. 2005;3:593–6.CrossRefGoogle Scholar
  52. Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007;25:1824–31.PubMedCrossRefGoogle Scholar
  53. Extermann M, Overcash J, Lyman GH, et al. Comorbidity and functional status are independent in older cancer patients. J Clin Oncol. 1998;16:1582–7.PubMedCrossRefGoogle Scholar
  54. Extermann M, Aapro M, Bernabei R, et al. Use of comprehensive geriatric assessment in older cancer patients: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG). Crit Rev Oncol Hematol. 2005;55:241–52.PubMedCrossRefGoogle Scholar
  55. Extermann M, Boler I, Reich R, Lyman GH, Brown RH, DeFelice J, et al. Predicting the risk of chemotherapy toxicity in older patients: the chemotherapy risk assessment scale for high-age patients (CRASH) score. Cancer. 2012;118:3377–86.PubMedCrossRefGoogle Scholar
  56. Feugier P, Van Hoof A, Sebban C, et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol. 2005;23:4117–26.PubMedCrossRefGoogle Scholar
  57. Fields FA, Townsend W, Webb A, et al. DeNovo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United Kingdom National Cancer Research Institute project. J Clin Oncol. 2014;32:282–7.PubMedCrossRefGoogle Scholar
  58. Fisher RI, Gaynor ER, Dahlberg S, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993;328:1002–6.PubMedCrossRefGoogle Scholar
  59. Fontan L, Yang C, Kabaleeswaran V, et al. MALT1 small molecule inhibitors specifically suppress ABC-DLBCL in vitro and in vivo. Cancer Cell. 2012;22:812–24.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Fridrik MA, Jaeger U, Petzer A, Willenbacher W, Keil F, Lang A, Andel J, Burgstaller S, Krieger O, Oberagner W, Sihorsch K, Greil R. Cardiotoxicity with rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine, and prednisolone in frontline treatment of patients with diffuse large B-cell lymphoma. A randomized phase-III study from the Austrian Cancer Drug Therapy Working Group [Arbeitgemeinschaft Medikamentose Tumortherapie AGMT] (NHL-14). Eur J Cancer. 2016;58:112–21.PubMedCrossRefGoogle Scholar
  61. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–56.PubMedCrossRefGoogle Scholar
  62. Friedberg JW. Relapsed/refractory diffuse large B-cell lymphoma. Hematology Am Soc Hematol Educ Program. 2011;2011:498–505.PubMedGoogle Scholar
  63. Friedberg JW, Unger JM, Burack WR, Gopal AK, Raju RN, Nademanee AP, Kaminski MS, Li H, Press OW, Miller TP, Fisher RI. R-CHOP with iodine-131 tositumomab for advanced stage diffuse large B-cell lymphoma (DLBCL) : SWOG S0433. Br J Haematol. 2014;166:382–9.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Gang AO, Pederson M, d’Amore F, Pederson LM, Jensen BA, Jensen P, Moller MB, Mourits-Anderson HT, Pederson RS, Klausen TW, Brown PDN. A clinically based prognostic index for diffuse large B-cell lymphoma with a cut-off at 70 years of age significantly improves prognostic stratification: population-based analysis from thr Danish Lymphoma Registry. Leuk Lymphoma. 2015;56:2556–62.PubMedCrossRefGoogle Scholar
  65. Garcia-Suarez J, Flores E, Callejas M, Arribas I, Gil-Fernandez JJ, Olmedilla G, Curto N, Guillen H, Casco CR, Martin Y, Burgaleta C. Two-weekly dose-djusted (DA)-EPOCH-like chmeotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma. Br J Haematol. 2013;160:510–4.PubMedCrossRefGoogle Scholar
  66. 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;28:4184–90.PubMedPubMedCentralCrossRefGoogle Scholar
  67. Gisselbrecht C, Schmitz N, Mounier N, Singh GD, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Duhrsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Briere J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed aggressive lymphoma. J Clin Oncol. 2012;30:4462–9.PubMedPubMedCentralCrossRefGoogle Scholar
  68. Goede V, Schulz RJ. Geriatric assessment in older adults with aggressive lymphoma: growing evidence and new emerging questions. Leuk Lymphoma. 2015;56:835–6.PubMedCrossRefGoogle Scholar
  69. Gomez H, Hidalgo M, Casanova L, et al. Risk factors for treatment-related death in elderly patients with aggressive non-Hodgkin’s lymphoma: results of a multivariate analysis. J Clin Oncol. 1998;16:2065–9.PubMedCrossRefGoogle Scholar
  70. Gopal AK, Press OW, Shustov AR, et al. Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget sound oncology consortium. Leuk Lymphoma. 2010;51:1523–9.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Gratzinger D, Advani R, Zhao S, Talreja N, Tibshirani RJ, Shyam R, et al. Lymphoma cell VEGFR2 expression detected by immunohistochemistry predicts poor overall survival in diffuse large B cell lymphoma treated with immunochemotherapy (R-CHOP). Br J Haematol. 2010;148:235–44.PubMedCrossRefGoogle Scholar
  72. Guglielmi C, Gomez F, Philip T, et al. Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial. J Clin Oncol. 1998;16:3264–9.PubMedCrossRefGoogle Scholar
  73. 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.PubMedCrossRefGoogle Scholar
  74. Hainsworth JD, Flinn IW, Spigel DR, et al. Brief-duration rituximab/chemotherapy followed by maintenance rituximab in patients with diffuse large B-cell lymphoma who are poor candidates for R-CHOP chemotherapy:a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma Leuk. 2010;10:44–50.PubMedCrossRefGoogle Scholar
  75. Haioun C, Mounier N, Emile JF, Ranta D, zCoiffier B, Tilly H, Recher C, Ferme C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009;20:1985–92.PubMedCrossRefGoogle Scholar
  76. Hamlin PA, Zelenetz AD, Kewalramani T, et al. Age-adjusted international prognostic index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2003;102:1989–96.PubMedCrossRefGoogle Scholar
  77. 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.PubMedCrossRefGoogle Scholar
  78. Hara T, Tsurumi H, Goto N, et al. Serum soluble Fas level determines clinical outcome of patients with diffuse large B-cell lymphoma treated with CHOP and R-CHOP. J Cancer Res Clin Oncol. 2009;135:1421–8.PubMedCrossRefGoogle Scholar
  79. Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994;84:1361–92.PubMedPubMedCentralGoogle Scholar
  80. Hasselblom S, Stenson M, Werlenius O, Sender M, Lewerin C, Hansson U, Nilsson-Ehle H, Andersson PO. Improved outcome for the very elderly patients with diffuse large B-cell lymphoma in the immunochemotherapy era. Leuk Lymphoma. 2012;53:394–9.PubMedCrossRefGoogle Scholar
  81. Held G, Murawski N, Ziepert M, et al. Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. J Clin Oncol. 2014;32:1112–8.PubMedCrossRefGoogle Scholar
  82. Hemminki K, Lenner P, Sundquist J, Bermejo JL. Risk of subsequent solid tumors after non-Hodgkin’s lymphoma: effect of diagnostic age and time since diagnosis. J Clin Oncol. 2008;26:1850–7.PubMedCrossRefGoogle Scholar
  83. Hershman DL, McBride RB, Eisenberger A, et al. Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin’s lymphoma. J Clin Oncol. 2008;26:3159–65.PubMedCrossRefGoogle Scholar
  84. 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. 2011;24:1046–54.PubMedCrossRefGoogle Scholar
  85. Horn J, Kleber M, Hieke S, et al. Treatment option of bendamustine in combination with rituximab in elderly and frail patients with aggressive B-non-Hodgkin lymphoma: rational, efficacy, and tolerance. Ann Hematol. 2012;91:1579–86.PubMedCrossRefGoogle Scholar
  86. Horn H, Ziepert M, Becher C, Barth TF, Bernd HW, Feller AC, et al. MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma. Blood. 2013;121:2253–63.PubMedCrossRefGoogle Scholar
  87. Horning SJ, Weller E, Kim K, et al. Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin’s lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol. 2004;22:3032–8.PubMedCrossRefGoogle Scholar
  88. Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Altekruse SF, Kosary CL, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER cancer statistics review, 1975–2009 (Vintage 2009 Populations), National Cancer Institute. Bethesda, http://seer.cancer.gov/csr/1975_2009_pops09/, based on November 2011 SEER data submission, posted to the SEER web site, April 2012.
  89. Huang BT, Zeng QC, Yu J, et al. How to determine post-RCHOP therapy for risk-tailored adult patients with diffuse large B-cell lymphoma, addition of maintenance rituximab or observation: multicenter experience. J Cancer Res Clin Oncol. 2012;138:125–32.PubMedCrossRefGoogle Scholar
  90. Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29:3457–65.PubMedPubMedCentralCrossRefGoogle Scholar
  91. Jacobson JO, Grossbard M, Schulman N, Neuberg D. CHOP chemotherapy with preemptive granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin’s lymphoma: a dose-intensity analysis. Clin Lymphoma. 2000;1:211–7.PubMedCrossRefGoogle Scholar
  92. Jaeger U, Trneny M, Melzer H, Praxmarer M, Nawarawong W, Yehuda DB, Goldstein D, Mihaljevic B, Ilhan O, Ballova V, Hedenus M, Hsaio LT, AU WY, Burgstaller S, Weidinger G, Keil F, Dittrich C, Skrabs C, Klinger A, Chott A, Fridrik MA, Greil R. Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial. Haematologica. 2015;100:955–63.PubMedPubMedCentralCrossRefGoogle Scholar
  93. Jaffe ES. The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Hematology. 2009;1:523–31.CrossRefGoogle Scholar
  94. Jais JP, Haioun C, Molina TJ, et al. The expression of 16 genes related to the cell of origin and immune response predicts survival in elderly patients with diffuse large B-cell lymphoma treated with CHOP and rituximab. Leukemia. 2008;22:1917–24.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Janssen-Heijnen ML, van Spronsen DJ, Lemmens VE, Huterman S, Verheij KD, Coebergh JW. A population-based study of severity of comorbidity among patients with non-Hodgkin’s lymphoma: prognostic impact independent of international prognostic index. Br J Haematol. 2005;129:597–606.PubMedCrossRefGoogle Scholar
  96. 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.PubMedCrossRefGoogle Scholar
  97. Jerkeman M, Anderson H, Dictor M, Kvaloy S, Akerman M, Cavallin-Stahl E. Assessment of biological prognostic factors provides clinically relevant information in patients with diffuse large B-cell lymphoma – a Nordic lymphoma group study. Ann Hematol. 2004;83:414–9.PubMedCrossRefGoogle Scholar
  98. Jung HA, Park S, Cho JH, Ko YH, Kim SJ, Kim WS. Prognostic relevance of pretreatment quality of life in diffuse large B-cell lymphoma patients treated with rituximab-CHOP : results from a prospective cohort study. Ann Hematol. 2012;91:1747–56.PubMedCrossRefGoogle Scholar
  99. Jung SH, Lee JJ, Kim WS, Lee WS, Do YR, Oh SY, Kim MK, Mun YC, Shin HJ, Kwak JY, Kang HJ, Won JH, Kwon JH, Park E, Suh C, Yang DH. Weekly rituximab consolidation following four cycles of R-CHOP induction chemotherapy in very eldserly patients with diffuse large B-cell lymphoma: consortium for improving survival of lymphoma study (CISL). Eur J Haematol. 2014;94:504–10.PubMedCrossRefGoogle Scholar
  100. Kaminski MS, Coleman CN, Colby TV, et al. Factors predicting survival in adults with stage I and II large-cell lymphoma treated with primary radiation therapy. Ann Intern Med. 1986;104:747–56.PubMedCrossRefGoogle Scholar
  101. Kemeny MM. Surgery in older patients. Semin Oncol. 2004;31:175–84.PubMedCrossRefGoogle Scholar
  102. Kewalramani T, Zelenetz AD, Nimer SD, et al. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004;103:3684–8.PubMedCrossRefGoogle Scholar
  103. Kuderer NM, Dale DC, Crawford J, et al. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer. 2006;106:2258–66.PubMedCrossRefGoogle Scholar
  104. Launay-Vacher V, Chatelut E, Lichtman SM, Wildiers H, Steer C, Aapro M, International Society of Geriatric Oncology. Renal insufficiency in elderly cancer patients: International Society of Geriatric Oncology clinical practice recommendations. Ann Oncol. 2007;18:1314–21.PubMedCrossRefGoogle Scholar
  105. Lazarus HM, Carreras J, Boudreau C, et al. Influence of age and histology on outcome in adult non-Hodgkin lymphoma patients undergoing autologous hematopoietic cell transplantation (HCT): a report from the Center for International Blood & Marrow Transplant Research (CIBMTR). Biol Blood Marrow Transplant. 2008;14:1323–33.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 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. 2008a;105:13520–5.PubMedPubMedCentralCrossRefGoogle Scholar
  107. Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, et al. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med. 2008b;359:2313–23.PubMedCrossRefGoogle Scholar
  108. Lichtman SM. Therapy insight: therapeutic challenges in the treatment of elderly cancer patients. Nat Clin Pract Oncol. 2006;3:86–93.PubMedCrossRefGoogle Scholar
  109. Lichtman SM, Wildiers H, Launay-Vacher V, Steer C, Chatelut E, Aapro M. International Society of Geriatric Oncology (SIOG) recommendations for the adjustment of dosing in elderly cancer patients with renal insufficiency. Eur J Cancer. 2007;43:14–34.PubMedCrossRefGoogle Scholar
  110. Lignon J, Sibon D, Madelaine I, et al. Rituximab, dexamethasone, cytarabine, and oxaliplatin (R-DHAX) is an effective and safe salvage regimen in relapsed/refractory B-cell non-Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk. 2010;10:262–9.PubMedCrossRefGoogle Scholar
  111. Lim ST, Hee SW, Quek R, et al. Performance status is the single most important prognostic factor in lymphoma patients aged greater than 75 overriding other prognostic factors such as histology. Leuk Lymphoma. 2008;49:149–51.PubMedCrossRefGoogle Scholar
  112. Lugtenburg P, Silvestre AS, Rossi FG, Noens L, Krall W, Bendall K, Szabo Z, Jaeger U. Impact of age group on febrile neutropenia risk assessment nd management in patients with diffuse large B-cell lymphoma treated with R-CHOP regimens. Clin Lymphoma Myeloma Leuk. 2012;12:297–305.PubMedCrossRefGoogle Scholar
  113. Lunning MA, Armitage JO. Rituximab maintenance therapy in diffuse large B-cell lymphoma: is XY the most important variable? Haematologica. 2015;100:853–5.PubMedPubMedCentralCrossRefGoogle Scholar
  114. Lyman GH, Delgado DJ. Risk and timing of hospitalization for febrile neutropenia in patients receiving CHOP, CHOP-R, or CNOP chemotherapy for intermediate-grade non-Hodgkin lymphoma. Cancer. 2003;98:2402–9.PubMedCrossRefGoogle Scholar
  115. Lyman GH, Morrison VA, Dale DC, et al. Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin’s lymphoma receiving CHOP chemotherapy. Leuk Lymphoma. 2003;44:2069–76.PubMedCrossRefGoogle Scholar
  116. Lyman GH, Kuderer NM, Crawford J, et al. Predicting individual risk of neutropenic complications in patients receiving cancer chemotherapy. Cancer. 2011;117:1917–27.PubMedCrossRefGoogle Scholar
  117. Marcheselli L, Marcheselli R, Bari A, et al. Radiation therapy improves treatment outcome in patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2011;52:1867–72.PubMedCrossRefGoogle Scholar
  118. Marcos-Gragera R, Allemani C, Tereanu C, et al. Survival of European patients diagnosed with lymphoid neoplasms in 2000-2002: results of the HAEMACARE project. Haematologica. 2011;96:720–8.PubMedPubMedCentralCrossRefGoogle Scholar
  119. Mareschal S, Lanic H, Ruminy P, et al. The proportion of activated B-cell like subtype among de novo diffuse large B-cell lymphoma increases with age. Haematologica. 2011;96:1888–90.PubMedPubMedCentralCrossRefGoogle Scholar
  120. Marx GM, Blake GM, Galani E, et al. Evaluation of the Cockroft-Gault, Jelliffe and Wright formulae in estimating renal function in elderly cancer patients. Ann Oncol. 2004;15:291–5.PubMedCrossRefGoogle Scholar
  121. McKelvey EM, Gottlieb JA, Wilson HE, et al. Hydroxy-daunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976;38:1484–93.PubMedCrossRefGoogle Scholar
  122. Merli F, luminari S, Rossi G, mammi C, Marcheselli L, Tucci A, Ilariucci F, Chiappella A, Musso M, Di Rocco A, Stelitano C, Alvarez I, Baldini L, Mazza P, Salvi F, Arcari a FA, Gobbi PG, Liberati AM, Federico M. Cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone, and rituximab fir the initial treatment of elderly ‘fit’ patients with diffue large B-celll lymphoma : results from the ANZINTER3 trial of the Intergruppo IItaliano Linfomi. Leuk Lymphoma. 2012;53:581–8.PubMedCrossRefGoogle Scholar
  123. Merli F, Luminari S, Rossi G, Mammi C, Marcheselli L, Ferrati A, Spins M, Tucci A, Stelitano C, Capodanno I, Fragasso A, Baldini L, Botelli C, Montechiarello E, Fogazzi S, Lamorgese C, Cavalli L, Federico M. Outcome of elderly frail patients with diffuse large B-cell lymphoma prospectively identified by comprehensive geriatric assessment: results from a study of the Fondazione Italiana Linfomi. Leuk Lymphoma. 2014;55:38–43.PubMedCrossRefGoogle Scholar
  124. Meyer RM, Browman GP, Samosh ML, et al. Randomized phase II comparison of standard CHOP with weekly CHOP in elderly patients with non-Hodgkin’s lymphoma. J Clin Oncol. 1995;13:2386–93.PubMedCrossRefGoogle Scholar
  125. Mikhaeel NG. Is 70 the new 60? New international prognostic index with an older age cut-off for diffuse large B-cell lymphoma. Leuk Lymphoma. 2015;56:2487–8.PubMedCrossRefGoogle Scholar
  126. Miller TP. The limits of limited stage lymphoma. J Clin Oncol. 2004;22:2982–4.PubMedCrossRefGoogle Scholar
  127. Miller TP, Grogan TM, Dahlberg S, Spier CM, Braziel RM, Banks PM, et al. Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: a prospective Southwest Oncology Group trial. Blood. 1994;83:1460–6.PubMedGoogle Scholar
  128. Miller TP, Dahlberg S, Cassaday 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.PubMedCrossRefGoogle Scholar
  129. Miller TP, LeBlanc M, Spier CM, et al. CHOP alone compared to CHOP plus radiotherapy for early stage aggressive non-Hodgkin’s lymphoma: update of the Southwest Oncology Group (SWOG) randomized trial. Blood. 2001;98:724a. (Abstract)CrossRefGoogle Scholar
  130. Miller TP, Unger JM, Spier CM, et al. Effect of adding ibritumomab tiuxetan (zevalin) radioimmunotherapy consolidation to three cycles of CHOP plus involved-field radiotherapy for limited-stage aggressive diffuse B-cell lymphoma (SWOG 0313). Blood. 2008;112:11. (Abstract 3598)CrossRefGoogle Scholar
  131. Monfardini S, Aversa SM, Zoli V, et al. Vinorelbine and prednisone in frail elderly patients with intermediate-high grade non- Hodgkin's lymphomas. Ann Oncol. 2005;16:1352–8.PubMedCrossRefGoogle Scholar
  132. Monnereau A, Troussard X, Belot A, Guizard AV, Woronoff AS, Bara S, et al. Unbiased estimates of long-term net survival of hematological malignancy patients detailed by major subtypes in France. Int J Cancer. 2013;132:2378–87.PubMedCrossRefGoogle Scholar
  133. Morrison VA, Hong F, Habermann TM, et al. R-CHOP versus (vs) CHOP followed by maintenance rituximab (MR) vs observation in older diffuse large B-cell lymphoma (DLBCL) patients: long-term follow-up of intergroup E4494/C9793. Blood. 2010;116:260. (Abstract 589)Google Scholar
  134. Morrison VA, Hamlin P, Soubeyran P, Stauder R, Wadhwa P, Aapro M, Lichtman S. Diffuse large B-cell lymphoma in the elderly: impact of prognosis, comorbidities, geriatric assessment, and supportive care. An International Society of Geriatric Oncology (SIOG) expert position paper. J Geriatr Oncol. 2015a;6:141–52.PubMedCrossRefGoogle Scholar
  135. Morrison VA, Hamlin P, Soubeyran P, Stauder R, Wadhwa P, Aapro M, Lichtman S. Approach to therapy of diffuse large B-cell lymphoma in the elderly: the International Society of Geriatric Oncology (SIOG) expert position commentary. Ann Oncol. 2015b;26:1058–68.PubMedCrossRefGoogle Scholar
  136. Morrison VA, Weller E, Habermann T, Li S, Fisher R, Cheson B, Peterson B. Patterns of growth factor usage and febrile neutropenia among older patients with diffuse large B-cell lymphoma treated with CHOP or R-CHOP: the intergroup experience (CALGB 9792; ECOG/SWOG 4494). Leuk Lymphoma. 2017;58:1814.PubMedCrossRefGoogle Scholar
  137. Mounier N, Briere J, Gisselbrecht C, Emile JF, Lederlin P, Sebban C, et al. Rituximab plus CHOP (R-CHOP) overcomes bcl-2 – associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL). Blood. 2003;101:4279–84.PubMedCrossRefGoogle Scholar
  138. Mounier N, Canals C, Gisselbrecht C, et al. High-dose therapy and autologous stem cell transplantation in first relapse for diffuse large B cell lymphoma in the rituximab era: an analysis based on data from the European Blood and Marrow Transplantation Registry. Biol Blood Marrow Transplant. 2012;18:788–93.PubMedCrossRefGoogle Scholar
  139. Mudie NY, Swerdlow AJ, Higgins CD, et al. Risk of second malignancy after non-Hodgkin’s lymphoma: a British cohort study. J Clin Oncol. 2006;24:1568–74.PubMedCrossRefGoogle Scholar
  140. Murawski N, Pfreundschuh M, Zeynalova S, Poeschel V, Hanel M, Held G, Schmitz N, Viardot A, Schmidt C, Hallek M, Witzens-Harig M, Trumper L, Rixecker T, Zwick C. Optimization of rituximab for the treatment of DLBCL (I): dose-dense rituximab in the DENSE-R-CHOP-14 trial of the DSHNHL. Ann Oncol. 2014;25:1800–6.PubMedCrossRefGoogle Scholar
  141. 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.PubMedCrossRefGoogle Scholar
  142. Nabhan C, Smith SM, Helenowski I, Ramsdale E, Parsons B, Karmali R, et al. Analysis of very elderly (≥80 years) non-hodgkin lymphoma: impact of functional status and co-morbidities on outcome. Br J Haematol. 2012;156:196–204.PubMedCrossRefGoogle Scholar
  143. Niitsu N, Umeda M. Evaluation of long-term daily administration of oral low-dose etoposide in elderly patients with relapsing or refractory non-Hodgkin’s lymphoma. Am J Clin Oncol. 1997;20:311–4.PubMedCrossRefGoogle Scholar
  144. Nowakowski GS, LaPlant B, Macon WR, Reeder CB, Foran JM, Nelson GD, Thompson CA, Rivera CE, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Gascoyne RD, Habermann TM, Witzig TE. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-cell lymphoma: a phase II study. J Clin Oncol. 2014;33:251–7.PubMedCrossRefGoogle Scholar
  145. O’Connell JD, Harrington DP, Johnson GJ, Glick JH. Initial chemotherapy doses for elderly patients with malignant lymphoma. J Clin Oncol. 1986;4:1418.PubMedCrossRefGoogle Scholar
  146. O’Reilly S, Connors JM, Macpherson N, et al. Malignant lymphomas in the elderly. Clin Geriatr Med. 1997;13:251–63.PubMedCrossRefGoogle Scholar
  147. Odejide OO, Cronin AM, Davidoff AJ, LaCasce AS, Abel GA. Limited stage diffuse large B-cell lymphoma: comparative effectiveness of treatment strategies in a large cohort of elderly patients. Leuk Lymphoma. 2015;56:716–24.PubMedCrossRefGoogle Scholar
  148. Offner F, Samoilova O, Osmanov E, Eom HS, Topp MS, Raposo J, Pavlov V, Ricci D, Chaturvedi S, Zhu E, van de Velde H, Enny C, Rizo A, Ferhanoglu B. Frontline rituximab, cyclophoshamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL. Blood. 2015;126:1893–901.PubMedPubMedCentralCrossRefGoogle Scholar
  149. Ohmachi K, Niitsu N, Uchida T, et al. Multicenter phase II study of bendamustine plus rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2013;31:2103–9.PubMedCrossRefGoogle Scholar
  150. Olszewski AJ, Mantripragada KC, Castillo JJ. Risk factors for early death after rituximab-based immunochemotherapy in older patients with diffuse large B-cell lymphoma. J Natl Compr Cancer Netw. 2016;14:1121–9.CrossRefGoogle Scholar
  151. Park SI, Grover NS, Olajide O, Asch AS, Wall JG, Richards KL, Sobol AL, Deal AM, Ivanova A, Foster MC, Muss HB, Shea TC. A phase II trial of bendamustine in combination with rituximab in older patients with previously untreated diffuse large B-cell lymphoma. Br J Haematol. 2016;175:281–9.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 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. 2008;26:2258–63.PubMedCrossRefGoogle Scholar
  153. 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.PubMedCrossRefGoogle Scholar
  154. Peyrade F, Bologna S, Delwail V, Emile JF, Pascal L, Fermé C, Schiano JM, Coiffier B, Corront B, Farhat H, Fruchart C, Ghesquieres H, Macro M, Tilly H, Choufi B, Delarue R, Fitoussi O, Gabarre J, Haioun C, Jardin F. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group. Lancet Oncol. 2017;4:e46–55.Google Scholar
  155. Pfreundschuh M. How I treat elderly patients with diffuse large B-cell lymphoma. Blood. 2010;116:5103–10.PubMedCrossRefGoogle Scholar
  156. Pfreundschuh M, Trumper L, Kloess M, et al. Two-weekly of 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. J Clin Oncol. 2004;104:634–41.Google Scholar
  157. 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.PubMedCrossRefGoogle Scholar
  158. Pfreundschuh M, Schubert J, Ziepert M, et al. German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). 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.PubMedCrossRefGoogle Scholar
  159. Pfreundschuh M, Kuhnt E, Truemper 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 randomized study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011;12:1013–22.PubMedCrossRefGoogle Scholar
  160. Pfreundschuh M, Poeschel V, Zeynalova S, Hanel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MHJ, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski M. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014a;32:4127–33.PubMedCrossRefGoogle Scholar
  161. Pfreundschuh M, Held G, Zeynalova S, et al. Increased rituximab (R) doses and effect on risk of elderly male patients with aggressive CD20+ B-cell lymphomas: results of the SEXIE-R-CHOP-14 trial of the DSHNHL. J Clin Oncol. 2014b;32:5s (Abstract 8501).CrossRefGoogle Scholar
  162. Phan J, Mazloom A, Medeiros JL, et al. Benefit of consolidative radiation therapy in patients with diffuse large B-cell lymphoma treated with R-CHOP chemotherapy. J Clin Oncol. 2010;28:4170–6.PubMedCrossRefGoogle Scholar
  163. Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM, Garcia-Marco JA, Castellvi J, Montes-Moreno S, Batlle A, de Villambrosia SG, Carnicero F, Ferrando-Lamana L, Piris MA, Lopez A. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma. A phase II study conducted by the Spanish PETHEMA group. Br J Haematol. 2015;169:188–98.PubMedCrossRefGoogle Scholar
  164. Raimondi R, Tosetto A, Oneto R, et al. Validation of the hematopoietic cell transplantation-specific comorbidity index: a prospective, multicenter GITMO study. Blood. 2012;120:1327–33.PubMedCrossRefGoogle Scholar
  165. Reddy S, Saxena VS, Pelletiere EV, et al. Early nodal and extra-nodal non-Hodgkin’s lymphomas. Cancer. 1977;40:98–104.PubMedCrossRefGoogle Scholar
  166. 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.PubMedCrossRefGoogle Scholar
  167. 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.PubMedCrossRefGoogle Scholar
  168. Rigacci L, Puccini B, Cortelazzo S, et al. Bendamustine with or without rituximab for the treatment of heavily pretreated non-Hodgkin’s lymphoma patients : a multicenter retrospective study on behalf of the Italian Lymphoma Foundation (FIL). Ann Hematol. 2012;91:1013–22.PubMedCrossRefGoogle Scholar
  169. Rizzo JD, Brouwers M, Hurley P, et al. American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer. Blood. 2010a;116:4045–59.PubMedCrossRefGoogle Scholar
  170. Rizzo JD, Brouwers M, Hurley P, et al. American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer. J Clin Oncol. 2010b;28:4996–5010.PubMedCrossRefGoogle Scholar
  171. Rodriguez J, Gutierrez A, Palacios A, et al. Rituximab, gemcitabine and oxaliplatin: an effective regimen in patients with refractory and relapsing mantle cell lymphoma. Leuk Lymphoma. 2007;48:2172–8.PubMedCrossRefGoogle Scholar
  172. Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, 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.PubMedCrossRefGoogle Scholar
  173. Ruan J, Martin P, Furman RR, Lee SM, Cheung K, Vose JM, LaCasce A, Morrison J, Elstrom R, Ely S, Chadburn A, Cesarman E, Coleman M, Leonard JP. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol. 2010;29:690–7.PubMedCrossRefGoogle Scholar
  174. Sant M, Allemani C, De AR, et al. Influence of morphology on survival for non-Hodgkin lymphoma in Europe and the United States. Eur J Cancer. 2008;44:579–87.PubMedCrossRefGoogle Scholar
  175. Sarif N, Joffe E, Gibstein L, Avivi I, Polliack A, Perry C, Herishanu Y, Reduced-dose ICE. Chemotherapy ± rituximab is a safe and effective salvage therapy for fit elderly patients with diffue large B-cell lymphoma. Leuk Lymphoma. 2016;57:1633–9.CrossRefGoogle Scholar
  176. Sarkozy C, Coiffier B. Duffuse large B-cell lymphoma in the elderly: a review of potential difficulties. Clin Cancer Res. 2013;19:1660–9.PubMedCrossRefGoogle Scholar
  177. Savage KJ, Johnson NA, Ben-Neriah S, Connors JM, Sehn LH, Farinha P, et al. MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy. Blood. 2009;114:3533–7.PubMedCrossRefGoogle Scholar
  178. Sehn LH, Donaldson J, Chhanabhai M, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol. 2005;23:5027–33.PubMedCrossRefGoogle Scholar
  179. Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, 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.PubMedCrossRefGoogle Scholar
  180. Sehn L, Savage K, Hoskins P, et al. Limited-stage DLBCL patients with a negative PET scan following three cycles of R-CHOP have an excellent outcome following abbreviated immuno-chemotherapy alone. Ann Oncol. 2008;19:iv99. (Abstract 052)CrossRefGoogle Scholar
  181. Shenkier TN, Voss N, Fairey R, et al. Brief chemotherapy and involved-region irradiation for limited-stage diffuse large-cell lymphoma: an 18-year experience from the British Columbia Cancer Agency. J Clin Oncol. 2002;20:197–204.PubMedCrossRefGoogle Scholar
  182. Shikama N, Oguchi M, Isobe K, et al. A prospective study of reduced-dose three-course CHOP followed by involved-field radiotherapy for patients 70 years old or more with localized aggressive non-Hodgkin’s lymphoma. Int J Radiat Oncol Biol Phys. 2006;66:217–22.PubMedCrossRefGoogle Scholar
  183. Siegel AB, Lachs M, Coleman M, et al. 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.PubMedCrossRefGoogle Scholar
  184. Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006;24:3187–205.PubMedCrossRefGoogle Scholar
  185. 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;105:1684–92.PubMedPubMedCentralCrossRefGoogle Scholar
  186. Solal-Celigny P, Chastang C, Herrera A, et al. Age as the main prognostic factor in adult aggressive non-Hodgkin’s lymphoma. Am J Med. 1987;83:1075–9.PubMedCrossRefGoogle Scholar
  187. Sonnen R, Schmidt WP, Kuse R, et al. Treatment results of aggressive B-non-Hodgkin’s lymphoma in advanced age considering comorbidity. Br J Haematol. 2002;119:634–9.PubMedCrossRefGoogle Scholar
  188. Sonneveld P, de Ridder M, van der Lelie H, et al. Comparison of doxorubicin and mitoxantrone in the treatment of elderly patients with advanced diffuse non-Hodgkin’s lymphoma using CHOP versus CNOP chemotherapy. J Clin Oncol. 1995;13:2530–9.PubMedCrossRefGoogle Scholar
  189. Sonneveld P, Huijgens SP, Hagenbeek A. Dose reduction is not recommended for elderly patients undergoing chemotherapy for non-Hodgkin lymphoma. Ned Tijdschr Geneeskd. 1999;143:418–9.PubMedGoogle Scholar
  190. Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9.PubMedPubMedCentralCrossRefGoogle Scholar
  191. Soubeyran P, Khaled H, MacKenzie M, et al. Diffuse large B-cell and peripheral T-cell non-Hodgkin’s lymphoma in the frail elderly: a phase II EORTC trial with a progressive and cautious treatment emphasizing geriatric assessment. J Geriatr Oncol. 2011;2:36–44.CrossRefGoogle Scholar
  192. Spicer J, Smith P, Maclennan K, et al. Long-term follow-up of patients treated with radiotherapy alone for early-stage histologically aggressive non-Hodgkin’s lymphoma. Br J Cancer. 2004;90:1151–5.PubMedPubMedCentralCrossRefGoogle Scholar
  193. Spina M, Balzarotti M, Uziel L, Ferreri AJM, Fratino L, Magagnoli M, Talamini R, Giacalone AA, Ravaioli E, Chimienti E, Berretta M, Lleshi A, Santoro A, Tirelli U. Modulated chemotherapy according to modified comprehensive geriatric assessment in 100 consecutive elderly patients with diffuse large B-cell lymphoma. Oncologist. 2012;17:838–46.PubMedPubMedCentralCrossRefGoogle Scholar
  194. Stephens DM, Li H, LeBlanc ML, Puvvada SD, Persky D, Friedberg JW, Smith SM. Continued risk of relapse independent of treatment modality in limited-stage diffuse large B-cell lymphoma: final and long-term analysis of Southwest Oncology Group Study S8736. J Clin Oncol. 2016;34:2997–3004.PubMedPubMedCentralCrossRefGoogle Scholar
  195. Stopek AT, Unger JM, Rimsza LM, LeBlanc M, Farnsworth B, Iannone M, Glenn MJ, Fisher RI, Miller TP. A phase 2 trial of standard-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab plus bevacizumab for ptients with newly dignosed diffuse large B-cell non-Hodgkin lymphoma: SWOG 0515. Blood. 2012;120:1210–7.CrossRefGoogle Scholar
  196. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993;329:987–94.Google Scholar
  197. The Non-Hodgkin’s Lymphoma Pathologic Classification Project. National Cancer Institute sponsored study of classification of non-Hodgkin’s lymphoma. Summary and description of a working formulation for clinical usage. Cancer. 1982;49:2112–35.CrossRefGoogle Scholar
  198. Thieblemont C, Coiffier B. Lymphoma in older patients. J Clin Oncol. 2007;25:1916–23.PubMedCrossRefGoogle Scholar
  199. 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. 2008;19:774–9.PubMedCrossRefGoogle Scholar
  200. 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;29:4079–87.PubMedCrossRefGoogle Scholar
  201. Tholstrup D, de Nully Brown P, Jurlander J, Hansen M. Feasibility, efficacy and safety of CHOP-14 in elderly patients with very high-risk diffuse large B-cell lymphoma. Eur J Haematol. 2007;79:100–6.PubMedCrossRefGoogle Scholar
  202. Tirelli U, Zagonel V, Serraino D, et al. Non-Hodgkin’s lymphomas in 137 patients aged 70 years or older: a retrospective European organization for research and treatment of cancer lymphoma group study. J Clin Oncol. 1988;6:1708–13.PubMedCrossRefGoogle Scholar
  203. Tirelli U, Errante D, Van Glabbeke M, et al. CHOP is the standard regimen in patients ≥ 70 years of age with intermediate-grade and high-grade non-Hodgkin’s lymphoma: results of a randomized study of the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Study Group. J Clin Oncol. 1998;16:27–34.PubMedCrossRefGoogle Scholar
  204. Tucci A, Ferrari S, Bottelli C, et al. 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.PubMedCrossRefGoogle Scholar
  205. Tucci A, Martelliu M, Rigacci L, et al. Comprehensive geriatric assessment is an essential tool to support treatment decisions in elderly patients with diffuse large B-cell lymphoma: a prospective multicenter evaluation in 173 patients by the Lymphoma Italian Foundation (FIL). Leuk Lymphoma. 2015;56:921–6.PubMedCrossRefGoogle Scholar
  206. Tward JD, Wendland MM, Shrieve DC, et al. The risk of secondary malignancies over 30 years after the treatment of non-Hodgkin lymphoma. Cancer. 2006;107:108–15.PubMedCrossRefGoogle Scholar
  207. Vacirca J. Bendamustine combined with rituximab for relapsed or refractory diffuse large B-cell lymphoma. Blood 2009; 114 (Suppl 1). (Abstract 4750).Google Scholar
  208. Vaidya R, Witzig TE. Prognotic factors for diffuse large B-cell lymphoma in the R(X)CHOP era. Ann Oncol. 2014;25:2124–33.PubMedPubMedCentralCrossRefGoogle Scholar
  209. Vaughan Hudson B, Vaughan Hudson G, MacLennan KA, Anderson L, Linch DC. Clinical stage 1 non-Hodgkin’s lymphoma: long-term follow-up of patients treated by the British National Lymphoma Investigation with radiotherapy alone as initial therapy. Br J Cancer. 1994;69:1088–93.PubMedPubMedCentralCrossRefGoogle Scholar
  210. 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.PubMedCrossRefGoogle Scholar
  211. 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.PubMedCrossRefGoogle Scholar
  212. Vitolo U, Chiappella A, Franceschetti S, Carella AM, Baldi I, Inghirami G, Spina M, Pavone V, Ladetto M, Liberati AM, Molinari AL, Zinzani P, Salvi F, Fattori PP Zaccaria A, Dreyling M, Botto B, Castellino A, Congiu A, Gaudiano M, Zanni M, Ciccone G, Gaidano G, Rossi G. Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncol. 2014;15:730–7.PubMedCrossRefGoogle Scholar
  213. Vose JM, Armitage JO, Weisenburger DD, et al. The importance of age in survival of patients treated with chemotherapy for aggressive non-Hodgkin’s lymphoma. J Clin Oncol. 1988;6:1838–44.PubMedCrossRefGoogle Scholar
  214. Vose JM, Link BK, Grossbard ML, et al. Phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated, aggressive non-Hodgkin’s lymphoma. J Clin Oncol. 2001;19:389–97.PubMedCrossRefGoogle Scholar
  215. Walter E, Schmitt T, Dietrich S, et al. Rituximab and bendamustine in patients with CD20+ diffuse large B-cell lymphoma not eligible for cyclophosphamide, doxorubicin, vincristine and prednisone-like chemotherapy. Leuk Lymphoma. 2012;53:2290–2.PubMedCrossRefGoogle Scholar
  216. Wang M, Fowler N, Wagner-Bartak N, et al. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular, and transformed lymphoma: a phase II clinical trial. Leukemia. 2013;27:1902–9.PubMedCrossRefGoogle Scholar
  217. Weidmann E, Kim SZ, Rost A, et al. Bendamustine is effective in relapsed or refractory aggressive non-Hodgkin’s lymphoma. Ann Oncol. 2002;13:1285–9.PubMedCrossRefGoogle Scholar
  218. 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. 2011;22:1839–44.PubMedCrossRefGoogle Scholar
  219. Wiernik PH, Lossos IS, Tuscano JM, et al. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin’s lymphoma. J Clin Oncol. 2008;26:4952–7.PubMedCrossRefGoogle Scholar
  220. Wildes TM, Augustin KM, Sempek D, et al. Comorbidities, not age, impact outcomes in autologous stem cell transplant for relapsed non-Hodgkin lymphoma. Biol Blood Marrow Transplant. 2008;14:840–6.PubMedCrossRefGoogle Scholar
  221. Wilson KS, Sehn LH, Berry B, Chhanabhai M, Fitzgerald CA, Gill KK, et al. CHOP-R therapy overcomes the adverse prognostic influence of BCL-2 expression in diffuse large B-cell lymphoma. Leuk Lymphoma. 2007;48:1102–9.PubMedCrossRefGoogle Scholar
  222. Wilson WH, Jung SH, Porcu P, Hurd D, Johnson J, Martin SE, Czuczman M, Lai R, Said J, Chadburn A, Jones D, Dunleavy K, Canellos G, Zelenetz AD, Cheson BD, Hsi ED. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of utcome by molecular subtype. Haematologica. 2012;97:758–65.PubMedPubMedCentralCrossRefGoogle Scholar
  223. Wilson WH, Jung SH, Pitcher BN, et al. Phase II randomized study of R-CHOP versus DA-EPOCH-R and molecular analysis of untreated large B-cell lymphoma: CALGB/alliance 50303. Blood. 2016;128(Suppl.) abstract 469Google Scholar
  224. Winkelmann N, Petersen I, Kiehntopf M, et al. Results of comprehensive geriatric assessment effect survival in patients with malignant lymphoma. J Cancer Res Clin Oncol. 2011;137:733–8.PubMedCrossRefGoogle Scholar
  225. Winter JN, Weller EA, Horning SJ, Krajewska M, Variakojis D, Habermann TM, et al. Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study. Blood. 2006;107:4207–13.PubMedPubMedCentralCrossRefGoogle Scholar
  226. Witzens-Harig M, Benner A, McClanahan F, Klemmer J, Brandt J, Brants E, Rieger M, Meissner J, Hensel M, Neben K, Dreger P, Lengfelder E, Schmidt-Wolf I, Kramer A, Ho AD. Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma. Results of the HD2002 prospective multicenter randomized phase III trial. Br J Haematol. 2015;171:710–9.PubMedCrossRefGoogle Scholar
  227. Witzig TE, Wiernik PH, Moore T, et al. Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin’s Lymphoma. J Clin Oncol. 2009;27:5404–9.PubMedCrossRefGoogle Scholar
  228. Witzig TE, Vose JM, Zinzani PL, et al. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin’s lymphoma. Ann Oncol. 2011;22:1622–7.PubMedCrossRefGoogle Scholar
  229. Witzig TE, Hong F, Micallef IN, Gascoyne RD, Dogan A, Wagner H, Kahl BS, Advani RH, Horning SJ. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell lymphoma: ECOG3402. Br J Haematol. 2015;170:679–86.PubMedPubMedCentralCrossRefGoogle Scholar
  230. Wolfson C, Wolfson DB, Asgharian M, et al. A reevaluation of the duration of survival after the onset of dementia. N Engl J Med. 2001;344:1111–6.PubMedCrossRefGoogle Scholar
  231. Xu-Monette ZY, Wu L, Visco C, Tai YC, Tzankov A, Lui W, et al. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL Rituximab-CHOP Consortium Program Study. Blood. 2012;120:3986–96.PubMedPubMedCentralCrossRefGoogle Scholar
  232. Yancik R, Wesley MN, Ries LA, et al. Comorbidity and age as predictors of risk for early mortality of male and female colon carcinoma patients: a population-based study. Cancer. 1998;82:2123–34.PubMedCrossRefGoogle Scholar
  233. Yao YY, Tang Y, Zhu Q, et al. Gemcitabine, oxaliplatin and dexamethasone as salvage treatment for elderly patients with refractory and relapsed peripheral T-cell lymphoma. Leuk Lymphoma. 2013;54:1194–2000.PubMedCrossRefGoogle Scholar
  234. Younes A, Thieblemont C, Morschhauser F, Flinn I, Friedberg JW, Amorim S, Hivert B, Westin J, Vermeulen J, Bandyopadhyay N, de Vries R, Balasubramanian S, Hellemens P, Smit JW, Fourneau N, Oki Y. Combintion of ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for treatment-naive patients with CD20-positive B-cell on-Hodgkin lymphoma:a non-randomised, phase 1b study. Lancet Oncol. 2014;15:1019–26.PubMedCrossRefGoogle Scholar
  235. Ziepert M, Hasenclever D, Kuhnt E, Glass B, Schmitz N, Prfeundschuh M, et al. J Clin Oncol. 2010;28:2372–80.CrossRefGoogle Scholar
  236. Zinzani PL, Rossi G, Franceschetti S, Botto B, Di Rocco A, Cabras MG, Petti MC, Stefoni V, Broccoli A, Fanti S, Pellegrini C, Montini GC, Gandolfi L, Derenzini E, Argnani L, Fina M, Tucci A, Botelli C, Pileri S, Baccarani M. Phase II trial of short course R-chop followed by 90Y-ibritumomab tiuxetan in previously untreated high-risk elderly difuse large B-cell lymphoma patients. Clin Cancer Res. 2010;16:3998–4004.PubMedCrossRefGoogle Scholar
  237. 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;11:462–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.University of MinnesotaMinneapolisUSA
  2. 2.Hematology/OncologyHennepin County Medical CenterMinneapolisUSA

Section editors and affiliations

  • Heidi Klepin
    • 1
  1. 1.Comprehensive Cancer Center of Wake Forest UniversityWinston-SalemUSA

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