Skip to main content
Log in

Management of Diffuse Large B-Cell Lymphoma in Young Patients

  • Therapy in Practice
  • Published:
American Journal of Cancer

Abstract

For more than 25 years, chemotherapy with the CHOP (cyclophosphamide, doxombicin, vincristine, and prednisone) regimen set the standard for the treatment of aggressive lymphomas. The recognition that treatment results depend mainly on patient selection led to the identification of pretreatment factors that allowed for the definition of prognostic subgroups based on the number of risk factors according to the International Prognostic Index (IPI). According to the IPI, ‘young’ patients are those up to 60 years of age. Young good-prognosis patients comprise the low and low-intermediate risk group (0 and 1 risk factor according to the age-adjusted IPI), and poor-prognosis patients comprise the high-intermediate and high-risk groups (≥2 risk factors).

While some improvement has been achieved by the addition of etoposide to CHOP and by shortening the treatment interval from 3 to 2 weeks (CHOEP-14), the best results in young good-prognosis patients have been achieved with six cycles of CHOP-like chemotherapy in combination with the anti-CD20 antibody rituximab. With this approach, 2-ycar event-free survival (EFS) rates of >90% and overall survival (OS) of 95% have been achieved in the ‘very favorable’ prognostic subgroup of patients (patients without an IPI risk factor and no bulky disease), while further improvement is needed for those in the ‘less favorable’ subgroup (IPI score = 1 and/or bulky disease; 2-year EFS: 77%). The role of additional radiotherapy in this setting remains to be determined.

For young poor-prognosis patients, the 5-ycar survival is around 50%, and progress has not been convincingly and specifically demonstrated in these patients. Ongoing studies will determine whether dose-dense conventional or high-dose chemotherapy regimens requiring stem-cell support in combination with rituximab will result in similar improvements for young poor-prognosis patients, as has been recently demonstrated for young patients with good-prognosis aggressive lymphoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I
Fig. 1
Fig. 2
Table II
Table III
Table IV

Similar content being viewed by others

References

  1. A predictive model for aggressive non-Hodgkin’s lymphoma: the International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med 1993; 329 (14): 987-94

  2. Pfreundschuh M, Trumper L, Kloess M, et al. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood 2004; 104: 626–33

    Article  PubMed  CAS  Google Scholar 

  3. Pfreundschuh M, Trümper LCD, Österborg A, et al. First analysis of the completed Mabthera International (MInT) trial in young patients with low-risk diffuse large B-cell lymphoma (DLBCL): addition of rituximab to a CHOP-like regimen significantly improves outcome of all patients with the identification of a very favorable subgroup with IPI = 0 and no bulky disease [abstract]. Blood 2.004; 104: 48a

  4. Martelli M, Gherlinzoni F, De Renzo A, et al. Early autologous stem-cell transplantation versus conventional chemotherapy as front-line therapy in high-risk, aggressive non-Hodgkin’s lymphoma: an Italian multicenter randomized trial. J Clin Oncol 2003; 21: 1255–62

    Article  PubMed  Google Scholar 

  5. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000; 403: 503–11

    Article  PubMed  CAS  Google Scholar 

  6. Shipp MA, Ross KN, Tamayo P, et al. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med 2002; 8: 68–74

    Article  PubMed  CAS  Google Scholar 

  7. Rosenwald A, Wright G, Chan WC, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 2002; 346: 1937–47

    Article  PubMed  Google Scholar 

  8. Loeffler M, Shipp M. Stein H. 2. Report on the workshop: “clinical consequences of pathology and prognostic factors in aggressive NHL”. Ann Hematol 2001; 80 Suppl. 3: B8–12

    Google Scholar 

  9. Losses IS, Czerwinski DK, Alizadeh AA, et al. Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N Engl J Med 2004; 350: 1828–37

    Article  Google Scholar 

  10. 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

    Article  PubMed  CAS  Google Scholar 

  11. Miller TP. The limits of limited stage lymphoma. J Clin Oncol 2004; 22: 2982–4

    Article  PubMed  Google Scholar 

  12. Shipp MA, Klatt MM, Yeap B, et al. Patterns of relapse in large-cell lymphoma patients with bulk disease: implications for the use of adjuvant radiation therapy. J Clin Oncol 1989; 7: 613–8

    PubMed  CAS  Google Scholar 

  13. Vokes EE, Ultmann JE, Golomb HM, et al. Long-term survival of patients with localized diffuse histiocytic lymphoma. J Clin Oncol 1985; 3: 1309–17

    PubMed  CAS  Google Scholar 

  14. Hoederath A, Sack H, Stuschke M, et al. Radiotherapy of primary extranodal non-Hodgkin’s lymphoma of the head and neck region: results of a prospective multicenter study. Study Group NHL: early studies [in German]. Strahlenther Onkol 1996; 172: 356–66

    PubMed  CAS  Google Scholar 

  15. Vaughan Hudson B, Vaughan Hudson G, MacLennan KA, et al. 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 1994Jun; 69(6): 1088–93

    Article  Google Scholar 

  16. 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

    PubMed  CAS  Google Scholar 

  17. Tsang RW, Gospodarowicz MK. Management of localized (stage I and II) clinically aggressive lymphomas. Ann Hematol 2001; 80 Suppl 3: B66–72

    Google Scholar 

  18. Tondini C, Zanini M, Lombardi F, et al. Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or [I histologically aggressive non-Hodgkin’s lymphomas. J Clin Oncol 1993; 11: 720–5

    PubMed  CAS  Google Scholar 

  19. 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

    Article  PubMed  CAS  Google Scholar 

  20. 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.1 Med 1998; 339: 21–6

    Article  CAS  Google Scholar 

  21. Miller TP, LeBlanc M, Spier C, et al. CHOP alone compared to CHOP plus radiotherapy for early stage aggressive non-Hodgkin’s lymphomas: update of the Southwest Oncology Group randomized trial [abstract]. Blood 2001; 98: 724a

    Article  Google Scholar 

  22. 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

    Article  PubMed  CAS  Google Scholar 

  23. 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

    Article  PubMed  CAS  Google Scholar 

  24. Aviles A, Delgado S, Nambo MJ, et al. Adjuvant radiotherapy to sites of previous bulky disease in patients stage IV diffuse large cell lymphoma. Int J Radiat Oncol Biol Phys 1994; 30: 799–803

    Article  PubMed  CAS  Google Scholar 

  25. Rube C, Nguyen TP, Kloss M, et al. Consolidation radiotherapy to bulky disease in aggressive NHL: first results of the NHL B-94 trial of the DSHNHL. Ann Hematol 2001; 80 Suppl. 3: B84–5

    Google Scholar 

  26. Haioun C, Lepage E, Gisselbrecht C, et al. Comparison of autologous bone marrow transplantation with sequential chemotherapy for intermediate-grade and high-grade non-Hodgkin’s lymphoma in first complete remission: a study of 464 patients. Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol 1994; 12: 2543–51

    PubMed  CAS  Google Scholar 

  27. Santini G, Salvagno L, Leoni P, et al. VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin’s lymphoma: results of a prospective randomized trial by the non-Hodgkin’s Lymphoma Cooperative Study Group. J Clin Oncol 1998; 16: 2796–802

    PubMed  CAS  Google Scholar 

  28. Koppler H, Pflugcr KH, Eschenbach I, et al. Randomised comparison of CHOEP versus alternating hCHOP/IVEP for high-grade non-Hodgkin’s lymphomas: treatment results and prognostic factor analysis in a multi-centre trial. Ann Oncol 1994; 5: 49–55

    Article  PubMed  CAS  Google Scholar 

  29. 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

    Article  PubMed  CAS  Google Scholar 

  30. Pfreundschuh M, Ho A, Wolf M, et al. Treatment results of CHOP-21, CHOEP-21, MACOP-B and PMitCEBO with and without rituximab in young good-prognosis patients with aggressive lymphomas: rituximab as an ‘equalizer’ in the MInT study [abstract] J Clin Oncol 2005; 23: 566s

    Google Scholar 

  31. Miller TP, Unger JM, Spier C, et al. Effect of adding rituximab to three cycles of CHOP plus involved-field radiotherapy for limited-stage aggressive diffuse B-cell lymphoma (SWOG-0014) [abstract]. Blood 2004; 104: 48a

    Google Scholar 

  32. McKelvey EM, Gottlieb JA, Wilson HE, et al. Hydroxyldaunomycin (adriamycin) combination chemotherapy in malignant lymphoma. Cancer 1976; 38: 1484–93

    Article  PubMed  CAS  Google Scholar 

  33. JH, Coldman AJ. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 1979; 63: 1727–33

    PubMed  CAS  Google Scholar 

  34. Meyer RM, Hryniuk WM, Goodyear MD. The role of dose intensity in determining outcome in intermediate-grade non-Hodgkin’s lymphoma. J Clin Oncol 1991; 9: 339–47

    PubMed  CAS  Google Scholar 

  35. De Vita JrVT, Hubbard SM, Longo DL. The chemotherapy of lymphomas: looking back, moving forward — the Richard and Hinda Rosenthal Foundation award lecture. Cancer Res 1987; 47: 5810–24

    Google Scholar 

  36. Gordon LI, Harrington D, Andersen J, et al. Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin’s lymphoma. N Engl J Med 1992; 327: 1342–9

    Article  PubMed  CAS  Google Scholar 

  37. Miller TP, Dahlberg S, Weick IK, et al. Unfavorable histologies of non-Hodgkin’s lymphoma treated with ProMACE-CytaBOM: a groupwide Southwest Oncology Group study. J Clin Oncol 1990; 8: 1951–8

    PubMed  CAS  Google Scholar 

  38. Klimo P, Connors JM. MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med 1985; 102: 596–602

    PubMed  CAS  Google Scholar 

  39. 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

    Article  PubMed  CAS  Google Scholar 

  40. Tilly H, Mounier N, Lederlin P, et al. Randomized comparison of ACVBP and m-BACOD in the treatment of patients with low-risk aggressive lymphoma: the LNH87-1 study. Groupe d’Etudes des Lymphomes de l’Adulte. J Clin Oncol 2000; 18: 1309–15

    PubMed  CAS  Google Scholar 

  41. 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

    Article  PubMed  CAS  Google Scholar 

  42. Haioun C, Lepage E, Gisselbrecht C, et al. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin’s lymphoma: final analysis of the prospective LNH87-2 protocol. A groupe d’Etude des Lymphomes de l’Adulte study. J Clin Oncol 2000; 18: 3025–30

    PubMed  CAS  Google Scholar 

  43. Gisselbrecht C, Lepage E, Molina T, et al. Shortened first-line high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma. J Clin Oncol 2002; 20: 2472–9

    Article  PubMed  CAS  Google Scholar 

  44. Verdonck LF, vanPutten WL, Hagenbeek A, et al. Comparison of CHOP chemotherapy with autologous bone marrow transplantation for slowly responding patients with aggressive non-Hodgkin’s lymphoma. N Engl J Med 1995; 332: 1045–51

    Article  PubMed  CAS  Google Scholar 

  45. Kaiser U, Uebelacker I, Abel U, et al. Randomized study to evaluate the use of high-dose therapy as part of primary treatment for ‘aggressive’ lymphoma. J Clin Oncol 2002; 20: 4413–9

    Article  PubMed  CAS  Google Scholar 

  46. Kluin-Nelemans HC, Zagonel V, Anastasopoulou A, et al. Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin’s lymphoma: randomized phase III EORTC study. J Natl Cancer Inst 2001; 93: 22–30

    Article  PubMed  CAS  Google Scholar 

  47. Sertoli MR, for the NHL Cooperative Study Group. VACOP-B vs VACOP-B + high dose sequential therapy (HDS) for diffuse non Hodgkin’s lymphoma: final analysis of the NHL Cooperative Group (NHLCSG) [abstract no. 2270]. Proc Am Soc Clin Oncol 2003; 22: 564

    Google Scholar 

  48. Milpied N, Deconinck E, Gaillard F, et al. Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. N Engl J Med 2004; 350: 1287–95

    Article  PubMed  CAS  Google Scholar 

  49. Gianni AM, Bregni M, Siena S, et al. High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med 1997; 336: 1290–7

    Article  PubMed  CAS  Google Scholar 

  50. Shipp MA, Abeloff MD, Antman KH, et al. International consensus conference on high-dose therapy with hematopoietic stem cell transplantation in aggressive non-Hodgkin’s lymphomas: report of the jury. J Clin Oncol 1999; 17: 423–9

    PubMed  CAS  Google Scholar 

  51. Glass B, Kloess M, Engert A, et al. Mega-CHOEP repeated high dose therapy as treatment of aggressive NHL: critical impact of time scheduling [abstract]. Blood 2002; 104: 776a

    Google Scholar 

  52. 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 2005Aug 1; 23(22): 5027–33

    Article  PubMed  CAS  Google Scholar 

  53. Glass B, Kloess M, Engert A, et al. Dose esclated CHOP + etoposide and repetitive autologous stem cell transplantation (MegaCHOEP) with and without rituximab for primary treatment of aggressive NHL [abstract]. J Clin Oncol 2005; 23Suppl.: 598s

    Google Scholar 

  54. Wilson WH, Dunleavy K, Pittaluga S, et al. Dose-adjusted EPOCH rituximab is highly effective in the GCB and ABC subtypes of untreated diffuse large B-cell lymphoma [abstract]. Blood 2004; 104: 49a

    Google Scholar 

Download references

Acknowledgments

This work was financially supported by Deutsche Krebshilfe and Kompetenznetz Maligne Lymphome. Dr M. Pfreundschuh is on the Mabthera Advisory Board of Roche.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael Pfreundschuh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pfreundschuh, M. Management of Diffuse Large B-Cell Lymphoma in Young Patients. Am J Cancer 4, 349–357 (2005). https://doi.org/10.2165/00024669-200504060-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00024669-200504060-00002

Keywords

Navigation