Skip to main navigation menu Skip to main content Skip to site footer

Review article: Biomedical intelligence

Vol. 142 No. 0506 (2012)

Diagnosis and treatment of diffuse large B-cell lymphoma

  • Ulrich J. M. Mey
  • Felicitas Hitz
  • Andreas Lohri
  • Stefanie Pederiva
  • Christian Taverna
  • Alexander Tzankov
  • Oliver Meier
  • Karen Yeow
  • Christoph Renner
DOI
https://doi.org/10.4414/smw.2012.13511
Cite this as:
Swiss Med Wkly. 2012;142:w13511
Published
29.01.2012

Summary

Diffuse large B-cell lymphoma (DLBCL) is the most frequently-occurring type of malignant lymphoma in the Western world. It has an aggressive natural history, with a median survival of less than one year if left untreated. Immunochemotherapy regimens, consisting of the anti-CD20 antibody rituximab typically in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), are currently the treatment backbone. Despite remarkable progress in improving patient survival, clinical outcomes are still unsatisfactory for certain subsets of patients, including the elderly and very elderly and those with highly aggressive disease. This review outlines some of the current treatment strategies for DLBCL and discusses the main issues that affect clinical practice.

aaIPI = age-adjusted International Prognostic Index; ABC = activated B-cell – like; ACVBP = doxorubicin, cyclophosphamide, vincristine, bleomycin and prednisone; ASCO = American Society of Clinical Oncology; BCCA = British Columbia Cancer Agency; CALGB = Cancer and Leukaemia Group B; CEPP = cyclophosphamide, etoposide, procarbazine and prednisone; CHOEP = cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone; CHOP = cyclophosphamide, doxorubicin, vincristine and prednisone; CNS = central nervous system; CORAL = Collaborative Trial in Relapsed Aggressive Lymphoma; CR = complete response; CT = computerised tomography; DFS = disease-free survival; DLBCL = diffuse large B-cell lymphoma; DSHNHL = German High-Grade Non-Hodgkin's Lymphoma Study Group; EFS = event-free survival; EORTC = European Organization for Research and Treatment of Cancer; ESHAP = etoposide, solumedrol, high-dose cytarabine and platinum; EPOCH = etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin; ESMO = European Society for Medical Oncology; FIL = Italian Lymphoma Foundation; FISH = fluorescence in-situ hybridisation; GCB = germinal centre B-cell – like; G-CSF = granulocyte colony-stimulating factor; GELA = Groupe d'Etude des Lymphomes de l'Adulte; HDT = high dose therapy; HIV = human immunodeficiency virus; ICE = ifosfamide, carboplatin and etoposide; IFRT = involved-field radiation therapy; IPI = International Prognostic Index; LDH = lactate dehydrogenase; MInT = MabThera International Trial; NCCN = National Comprehensive Cancer Network; NHL = Non-Hodgkin’s lymphoma; NOS = not otherwise specified; OS = overall survival; PET = positron emission tomography; PMBL = primary mediastinal B-cell lymphoma; PFS = progression-free survival; R = rituximab; RICOVER-60 = Rituximab with CHOP over age 60 years; SCT = stem cell transplantation; SAKK = Schweizerische Arbeitsgruppe für Klinische Krebsforschung; SWOG = Southwest Oncology Group; WHO = World Health Organisation.

References

  1. Nogai H, Dorken B, Lenz G. Pathogenesis of Non-Hodgkin’s Lymphoma. J Clin Oncol. 2011;29:1803–11.
  2. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue (IARC WHO Classification of Tumours). World Health Organization. 2008; 4th edition.
  3. Campo E, Swerdlow SH, Harris NL, et al. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117:5019–32.
  4. Turner JJ, Hughes AM, Kricker A, et al. WHO non-Hodgkin’s lymphoma classification by criterion-based report review followed by targeted pathology review: an effective strategy for epidemiology studies. Cancer Epidemiol Biomarkers Prev. 2005;14:2213–9.
  5. Ott G, Ziepert M, Klapper W, et al. Immunoblastic morphology but not the immunohistochemical GCB/nonGCB classifier predicts outcome in diffuse large B-cell lymphoma in the RICOVER-60 trial of the DSHNHL. Blood. 2010;116:4916–25.
  6. Adams H, Liebisch P, Schmid P, et al. Diagnostic utility of the B-cell lineage markers CD20, CD79a, PAX5, and CD19 in paraffin-embedded tissues from lymphoid neoplasms. Appl Immunohistochem Mol Morphol. 2009;17:96–101.
  7. Tzankov A, Zlobec I, Went P, et al. Prognostic immunophenotypic biomarker studies in diffuse large B cell lymphoma with special emphasis on rational determination of cut-off scores. Leuk Lymphoma. 2010;51:199–212.
  8. Mounier N, Briere J, Gisselbrecht 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.
  9. Lenz G, Staudt LM. Aggressive lymphomas. N Engl J Med. 2010;362:1417–29.
  10. 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. 2010;28:3360–5.
  11. Obermann EC, Csato M, Dirnhofer S, et al. Aberrations of the MYC gene in unselected cases of diffuse large B-cell lymphoma are rare and unpredictable by morphological or immunohistochemical assessment. J Clin Pathol. 2009;62:754–56.
  12. Savage KJ, Johnson NA, Ben-Neriah S, 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.
  13. 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. 2008;26:2717–24.
  14. Dunleavy K, Pittaluga S, Czuczman MS, et al. Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma. Blood. 2009;113:6069–76.
  15. Fu K, Weisenburger DD, Choi WW, et al. Addition of rituximab to standard chemotherapy improves the survival of both the germinal center B-cell-like and non-germinal center B-cell-like subtypes of diffuse large B-cell lymphoma. J Clin Oncol. 2008;26:4587–94.
  16. Gutierrez-Garcia G, Cardesa-Salzmann T, Climent F, et al. Gene-expression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Blood. 2011;117:4836–43.
  17. 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.
  18. Gascoyne RD. Establishing the diagnosis of lymphoma: from initial biopsy to clinical staging. Oncology (Williston Park). 1998;12:11–6.
  19. 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 5):v172–v174.
  20. Niitsu N, Hagiwara Y, Tanae K, et al. Prospective analysis of hepatitis B virus reactivation in patients with diffuse large B-cell lymphoma after rituximab combination chemotherapy. J Clin Oncol. 2010;28:5097–100.
  21. Pfreundschuh M. How I treat elderly patients with diffuse large B-cell lymphoma. Blood. 2010;116:5103–10.
  22. Schaefer NG, Hany TF, Taverna C, et al. Non-Hodgkin lymphoma and Hodgkin disease: coregistered FDG PET and CT at staging and restaging – do we need contrast-enhanced CT? Radiology. 2004;232:823–9.
  23. Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25:579–86.
  24. Cheson BD. Role of functional imaging in the management of lymphoma. J Clin Oncol. 2011;29:1844–54.
  25. Cashen A, Dehdashti F, Luo J, et al. Poor predictive value of FDG-PET/CT performed after 2 cycles of R-CHOP in patients with Diffuse Large B-Cell Lymphoma (DLCL). Blood (ASH Annual Meeting Abstracts). 2008;112:Abstract 371.
  26. Gigli F, Nassi L, Negri M, et al. Interim 18f[FDG] positron emission tomography in patients with diffuse large B-cell lymphoma. Blood (ASH Annual Meeting Abstracts). 2008;112:Abstract 3609.
  27. 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.
  28. Mikhaeel NG, Hutchings M, Fields PA, et al. FDG-PET after two to three cycles of chemotherapy predicts progression-free and overall survival in high-grade non-Hodgkin lymphoma. Ann Oncol. 2005;16:1514–23.
  29. Pregno P, Chiappella A, Bello M, et al. Interim 18-FDG-Positron Emission Tomography/Computed Tomography (PET) failed to predict different outcome in Diffuse Large B-Cell Lymphoma (DLBCL) patients treated with rituximab-CHOP. Blood (ASH Annual Meeting Abstracts). 2009;114:Abstract 99.
  30. Safar V, Dupuis J, Jardin F, et al. Early 18fluorodeoxyglucose PET scan as a prognostic tool in diffuse large B-cell lymphoma patients treated with an anthracycline-based chemotherapy plus rituximab. Blood (ASH Annual Meeting Abstracts). 2009;114:Abstract 98.
  31. 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. 2002;13:1356–63.
  32. Mamot C, Klingbiel D, Renner C, et al. First results of a prospective evaluation of interim PET in patients with DLBCL treated with R-CHOP-14 (SAKK 38/07). Ann Oncol. 2011;22(Suppl 4):218.
  33. Wagner-Johnston ND, Bartlett NL. Role of routine imaging in lymphoma. J Natl Compr Canc Netw. 2011;9:575–84.
  34. Cheson BD. New response criteria for lymphomas in clinical trials. Ann Oncol. 2008;19(Suppl 4):iv35–iv38.
  35. Sehn L, Hoskins P, Klasa R, et al. FDG-PET scan guided consolidative radiation therapy optimizes outcome in patients with advanced-stage diffuse large B-cell lymphoma (DLBCL) with residual abnormalities on CT Scan Following R-CHOP. Blood (ASH Annual Meeting Abstracts). 2010;116:Abstract 854.
  36. Fisher RI, Miller TP, O’Connor OA. Diffuse aggressive lymphoma. Hematology Am Soc Hematol Educ Program. 2004;221–36.
  37. Cabanillas F. Front-line management of diffuse large B cell lymphoma. Curr Opin Oncol. 2010;22:642–5.
  38. 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.
  39. Coiffier B, Haioun C, Ketterer N, et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood. 1998;92:1927–32.
  40. Maloney DG, Grillo-Lopez AJ, White CA, et al. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood. 1997;90:2188–95.
  41. McLaughlin P, Grillo-Lopez AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16:2825–33.
  42. Coiffier B. State-of-the-art therapeutics: diffuse large B-cell lymphoma. J Clin Oncol. 2005;23:6387–93.
  43. 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.
  44. Feugier P, Van HA, 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.
  45. 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.
  46. 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.
  47. 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.
  48. 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.
  49. Cunningham D, Smith P, Mouncey W, et al. A phase III trial comparing R-CHOP 14 and R-CHOP 21 for the treatment of patients with newly diagnosed diffuse large B-cell non-Hodgkin's lymphoma. J Clin Oncol. (Meeting Abstracts). 2009;27:Abstract 8506.
  50. 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 (meeting abstracts). 2011;29:abstract 8000.
  51. Delarue R, Tilly H, Salles G, et al. R-CHOP14 compared to R-CHOP21 in elderly patients with diffuse large B-cell lymphoma (DLBCL): results of the second interim analysis of the LNH03-6B GELA study. Ann Oncol. 2011;22(Suppl. 4):Abstract 106.
  52. Pfreundschuh M, Zeynalova S, Poeschel V, et al. Dose-dense rituximab improves outcome of elderly patients with poor-prognosis Diffuse Large B-Cell Lymphoma (DLBCL): Results of the DENSE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Blood (ASH annual meeting abstracts). 2007;110:abstract 789.
  53. Pfreundschuh M, Murawski N, Zeynalova S, et al. Male Sex Is Associated with Lower Rituximab Trough Serum Levels and Evolves as a Significant Prognostic Factor in Elderly Patients with DLBCL Treated with R-CHOP: Results from 4 prospective trials of the German High-Grade Non-Hodgkin-Lymphoma Study Group (DSHNHL). Blood (ASH Annual Meeting Abstracts). 2009;114:Abstract 3715.
  54. Ribera JM. Hope for very elderly patients with diffuse large B-cell lymphoma. Lancet Oncol. 2011;12:412–3.
  55. Italiano A, Jardin F, Peyrade F, et al. Adapted CHOP plus rituximab in non-Hodgkin’s lymphoma in patients over 80 years old. Haematologica. 2005;90:1281–3.
  56. 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.
  57. 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.
  58. Flowers CR, Sinha R, Vose JM. Improving outcomes for patients with diffuse large B-cell lymphoma. CA Cancer J Clin. 2010;60:393–408.
  59. 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.
  60. 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;12:1013–21.
  61. 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.
  62. 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.
  63. Recher C, Coiffier B, Haioun C, et al. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011;378:1858–67.
  64. Brusamolino E, Rusconi C, Montalbetti L, et al. Dose-dense R-CHOP-14 supported by pegfilgrastim in patients with diffuse large B-cell lymphoma: a phase II study of feasibility and toxicity. Haematologica. 2006;91:496–502.
  65. Halaas JL, Moskowitz CH, Horwitz S, et al. R-CHOP-14 in patients with diffuse large B-cell lymphoma: feasibility and preliminary efficacy. Leuk Lymphoma. 2005;46:541–7.
  66. Wunderlich A, Kloess M, Reiser M, et al. Practicability and acute haematological toxicity of 2- and 3-weekly CHOP and CHOEP chemotherapy for aggressive non-Hodgkin's lymphoma: results from the NHL-B trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Ann Oncol. 2003;14:881–93.
  67. Gang AO, Strom C, Pedersen M, et al. R-CHOEP-14 improves overall survival in young high-risk patients with diffuse large B-cell lymphoma compared with R-CHOP-14. A population-based investigation from the Danish Lymphoma Group. Ann Oncol. 2011; Epub ahead of print.
  68. Dunleavy K, Pittaluga S, Wayne S, et al. Myc + agressive B-cell lymphomas: novel therapy of untreated Burkitt lymphoma (BL) and Myc+ diffuse large B-cell lymphoma (DLBCL) with DA-EPOCH-R. Ann Oncol. 2011;22(Suppl 4):071.
  69. Coiffier B, Reyes F. Best treatment of aggressive non-Hodgkin’s lymphoma: a French perspective. Oncology. (Williston Park). 2005;19:7–15.
  70. Fitoussi O, Belhadj K, Mounier N, et al. Survival impact of rituximab combined with ACVBP and upfront consolidative autotransplantation in high risk diffuse large B-cell lymphoma for GELA. Haematologica. 2011;96:1136–43.
  71. Greb A, Bohlius J, Schiefer D, et al. High-dose chemotherapy with autologous stem cell transplantation in the first line treatment of aggressive non-Hodgkin lymphoma (NHL) in adults. Cochrane Database Syst Rev. 2008;1:CD004024.
  72. Le Gouill S, Milpied N, Lamy T, et al. First-line rituximab (R) high-dose therapy (R-HDT) versus R-CHOP14 for young adults with diffuse large B-cell lymphoma: Preliminary results of the GOELAMS 075 prospective multicenter randomized trial. J Clin Oncol (Meeting Abstracts). 2011;29:Abstract 8003.
  73. 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 Lymphona Study Group (DSHNHL). J Clin Oncol (Meeting Abstracts). 2011;29:Abstract 8002.
  74. Vitolo U, Chiappella A, Brusamolino E, et al. A randomized multicentre phase III study for first line treatment of young patients with high risk (aaIPI 2-3) diffuse large B-cell lymphoma (DLBCL): Rituximab (R) plus dose-dense chemotherapy CHOP14/MegaCHOP14 with or without intensified high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Ann Oncol. 2011;22(Supplement 4):Abstract 072.
  75. 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 (Meeting Abstracts). 2011;29:Abstract 8001.
  76. Armitage JO. Treatment of non-Hodgkin's lymphoma. N Engl J Med. 1993;328:1023–30.
  77. 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.
  78. Miller TP, LeBlanc M, Spier CM, et al. CHOP alone compared to CHOP plus radiotherapy for early stage aggressive non-Hodgkin’s lymphomas: Update of the Southwest Oncology Group (SWOG) randomized trial. Blood (ASH Annual Meeting Abstracts). 2001;98:724a.
  79. 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.
  80. 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;20;346:1937–47.
  81. Sehn L, Savage KJ, Hoskins P, et al. Treatment of limited-stage DLBCL can be effectively tailored using a PET-based approach. Ann Oncol. 2011;22(Suppl. 4):Abstract 028.
  82. 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.
  83. 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.
  84. Persky DO, Miller TP. Localized large cell lymphoma: is there any need for radiation therapy? Curr Opin Oncol. 2009;21:401–6.
  85. Pfreundschuh M, Ho AD, Cavallin-Stahl E, et al. Prognostic significance of maximum tumour (bulk) diameter in young patients with good-prognosis diffuse large-B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: an exploratory analysis of the MabThera International Trial Group (MInT) study. Lancet Oncol. 2008;9:435–44.
  86. Pfreundschuh M, Ziepert M, Reiser M, et al. The role of radiotherapy to bulky disease in the rituximab era: results from two prospective trials of the German High-Grade Non-Hodgkin-Lymphoma Study Group (DSHNHL) for elderly patients with DLBCL. Blood (ASH Annual Meeting Abstracts). 2008;112:Abstract 584.
  87. Gisselbrecht C, Vose J, Nademanee A, et al. Radioimmunotherapy for stem cell transplantation in non-Hodgkin’s lymphoma: in pursuit of a complete response. Oncologist. 2009;14(Suppl 2):41–51.
  88. Mounier N, Gisselbrecht C. Stem cell transplantation for diffuse large B-cell lymphoma patients in the rituximab era. Curr Opin Oncol. 2011;23:209–13.
  89. 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.
  90. 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.
  91. Aviles A, Neri N, Huerta-Guzman J, et al. ESHAP versus rituximab-ESHAP in frail patients with refractory diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2010;10:125–8.
  92. Ueda K, Nannya Y, Asai T, et al. Efficacy and safety of modified rituximab-ESHAP therapy for relapsed/refractory B-cell lymphoma. J Chemother. 2010;22:54–7.
  93. Garcia-Suarez J, Banas H, Arribas I, et al. Dose-adjusted EPOCH plus rituximab is an effective regimen in patients with poor-prognostic untreated diffuse large B-cell lymphoma: results from a prospective observational study. Br J Haematol. 2007;136:276–85.
  94. Chao NJ, Rosenberg SA, and Horning SJ. CEPP(B): an effective and well-tolerated regimen in poor-risk, aggressive non-Hodgkin’s lymphoma. Blood. 1990;76:1293–8.
  95. Cortelazzo S, Rambaldi A, Rossi A, et al. Intensification of salvage treatment with high-dose sequential chemotherapy improves the outcome of patients with refractory or relapsed aggressive non-Hodgkin’s lymphoma. Br J Haematol. 2001;114:333–41.
  96. Persky DO, Moskowitz CH, Filatov A, et al. High dose chemoradiotherapy and ASCT may overcome the prognostic importance of biologic markers in relapsed/refractory Hodgkin lymphoma. Appl Immunohistochem Mol Morphol. 2010;18:35–40.
  97. Simpson L, Ansell SM, Colgan JP, et al. Effectiveness of second line salvage chemotherapy with ifosfamide, carboplatin, and etoposide in patients with relapsed diffuse large B-cell lymphoma not responding to cis-platinum, cytosine arabinoside, and dexamethasone. Leuk Lymphoma. 2007;48:1332–7.
  98. 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.
  99. 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.
  100. Murawski N, Pfreundschuh M. New drugs for aggressive B-cell and T-cell lymphomas. Lancet Oncol. 2010;11:1074–85.
  101. Khouri IF. Reduced-intensity regimens in allogeneic stem-cell transplantation for non-hodgkin lymphoma and chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2006;390–7.
  102. Peniket AJ, Ruiz de Elvira MC, Taghipour G, et al. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation. Bone Marrow Transplant. 2003;31:667–78.
  103. Maloney D. Allogeneic transplantation following nonmyeloablative conditioning for aggressive lymphoma. Bone Marrow Transplant. 2008;42(Suppl 1):S35–S36.
  104. Thomson KJ, Morris EC, Bloor A, et al. Favorable long-term survival after reduced-intensity allogeneic transplantation for multiple-relapse aggressive non-Hodgkin’s lymphoma. J Clin Oncol. 2009;27:426–32.
  105. Sirvent A, Dhedin N, Michallet M, et al. Low nonrelapse mortality and prolonged long-term survival after reduced-intensity allogeneic stem cell transplantation for relapsed or refractory diffuse large B cell lymphoma: report of the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. Biol Blood Marrow Transplant. 2010;16:78–85.
  106. Kenkre VP, Smith SM. Management of relapsed diffuse large B-cell lymphoma. Curr Oncol Rep. 2008;10:393–403.
  107. 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.
  108. Lopez A, Gutierrez A, Palacios A, et al. GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study. Eur J Haematol. 2008;80:127–32.
  109. Bjorkholm M, Hagberg H, Holte H, et al. Central nervous system occurrence in elderly patients with aggressive lymphoma and a long-term follow-up. Ann Oncol. 2007;18:1085–9.
  110. Hollender A, Kvaloy S, Nome O, et al. Central nervous system involvement following diagnosis of non-Hodgkin’s lymphoma: a risk model. Ann Oncol. 2002;13:1099–107.
  111. van Besien K, Ha CS, Murphy S, et al. Risk factors, treatment, and outcome of central nervous system recurrence in adults with intermediate-grade and immunoblastic lymphoma. Blood. 1998;91:1178–84.
  112. 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.
  113. 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.
  114. O’Rourke K, Morris K, Kennedy GA. 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;116:4283–90.
  115. Vitolo U, Chiappella A, Ferreri AJ, et al. First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial. J Clin Oncol. 2011;29:2766–72.
  116. Pui CH, Thiel E. Central nervous system disease in hematologic malignancies: historical perspective and practical applications. Semin Oncol. 2009;36:S2–S16.
  117. Korfel A. Prevention of central nervous system relapses in diffuse large B-cell lymphoma: which patients and how? Curr Opin Oncol. 2011;23:436–40.
  118. Villa D, Connors JM, Shenkier TN, et al. 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.
  119. 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.
  120. Boehme V, Zeynalova S, Kloess M, et al. Incidence and risk factors of central nervous system recurrence in aggressive lymphoma – a survey of 1693 patients treated in protocols of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Ann Oncol. 2007;18:149–57.
  121. Saloustros E, Tryfonidis K, Georgoulias V. Prophylactic and therapeutic strategies in chemotherapy-induced neutropenia. Expert Opin Pharmacother. 2011;12:851–63.
  122. 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.
  123. 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.
  124. Repetto L, Biganzoli L, Koehne CH, et al. EORTC Cancer in the Elderly Task Force guidelines for the use of colony-stimulating factors in elderly patients with cancer. Eur J Cancer. 2003;39:2264–72.

Most read articles by the same author(s)

<< < 1 2