Questions About Cancer? 1-800-4-CANCER
  • View entire document
  • Print
  • Email
  • Facebook
  • Twitter
  • Google+
  • Pinterest

Adult Non-Hodgkin Lymphoma Treatment (PDQ®)

Treatment for Indolent, Noncontiguous Stage II/III/IV Adult NHL

Optimal treatment of advanced stages of low-grade non-Hodgkin lymphoma (NHL) is controversial because of low cure rates with the current therapeutic options. Numerous clinical trials are in progress to settle treatment issues, and patients should be urged to participate. The rate of relapse is fairly constant over time, even in patients who have achieved complete response to treatment. Indeed, relapse may occur many years after treatment. Currently, no randomized trials guide clinicians about the initial choice of watchful waiting, rituximab, nucleoside analogs, alkylating agents, combination chemotherapy, radiolabeled monoclonal antibodies, or combinations of these options.[1]; [2][Level of evidence: 1iiDiii]

For patients with indolent, noncontiguous stage II and stage III non-Hodgkin lymphoma, central lymphatic radiation therapy has been proposed but is not usually recommended as a form of treatment.[3,4]

Numerous prospective clinical trials of interferon-alpha, including SWOG-8809, have shown no consistent benefit; the role of interferon in patients with indolent lymphoma remains controversial.[5-16]

Standard Treatment Options for Indolent, Noncontiguous Stage II/III/IV Adult NHL

Standard treatment options for indolent, noncontiguous stage II/III/IV adult NHL include the following:

Watchful waiting for asymptomatic patients

The rate of relapse is fairly constant over time, even in patients who have achieved complete responses to treatment. Indeed, relapse may occur many years after treatment. In this category, deferred treatment (i.e., watchful waiting until the patient becomes symptomatic before initiating treatment) should be considered.[2,17-19]

Evidence (watchful waiting):

  1. Three randomized trials compared watchful waiting with immediate chemotherapy.[18,20]; [21][Level of evidence: 1iiA]
    • All three trials showed no difference in cause-specific or overall survival (OS).
    • For patients randomly assigned to watchful waiting, the median time to require therapy was 2 to 3 years and one-third of patients never required treatment with watchful waiting (half died of other causes and half remained progression free after 10 years).
  2. A selected group of 107 patients with advanced stage follicular lymphoma were managed with initial watchful waiting; with a median delay of 55 months, subsequent therapy resulted in equivalent freedom from treatment failure and OS compared with a similar cohort treated immediately with rituximab.[22][Level of evidence: 3iiiDiii] This implies that watchful waiting remains a relevant approach even in the rituximab era.


Rituximab may be considered as first-line therapy, either alone or in combination with other agents.

  • Rituximab alone, as was shown in the ECOG-E4402 (NCT00075946) trial, for example.[23-27]
  • R-Bendamustine: rituximab + bendamustine.[28-30]
  • R-F: rituximab + fludarabine.[31]
  • R-CVP: rituximab + cyclophosphamide + vincristine + prednisone.[32,33]
  • R-CHOP: rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone.[34-36] A Cochrane meta-analysis could not identify any OS benefit to adding doxorubicin to chemotherapy regimens with rituximab or to chemotherapy regimens without rituximab.[37][Level of evidence: 1iiA]
  • R-FM: rituximab + fludarabine + mitoxantrone.[38]
  • R-FCM: rituximab + fludarabine + cyclophosphamide + mitoxantrone.[39]

Standard therapy includes rituximab, an anti-CD20 monoclonal antibody, either alone or in combination with purine nucleoside analogs such as fludarabine or 2-chlorodeoxyadenosine, alkylating agents (with or without steroids), or combination chemotherapy.

A prospective, randomized trial of 534 patients with previously untreated, advanced-stage follicular lymphoma compared R-CHOP, R-FM, and R-CVP. With a median follow-up of 34 months, there was no difference in OS, but the 3-year PFS favored R-CHOP (68%) and R-FM (63%) over R-CVP (52%) (P for the three regimens = .011).[40][Level of evidence: 1iiDiii]

Evidence (rituximab):

  • Four randomized, prospective studies of previously untreated patients (involving more than 1,300 patients) and one Cochrane meta-analysis including both untreated and previously treated patients (involving almost 1,000 patients) have compared rituximab plus combination chemotherapy with chemotherapy alone.[33,36,41]; [42,43][Level of evidence: 1iiA]
    • Rituximab plus chemotherapy was superior in terms of event-free survival or progression-free survival (PFS) (ranging from 2–3 years) in all of the studies and in terms of OS in all but one study (absolute benefit ranging from 6%–13% at 4 years, P < .04 and hazard ratio [HR] = 0.63 [0.51–0.79] for the meta-analysis).
    • All of these trials were performed in symptomatic patients who required therapy. These results do not negate watchful waiting when appropriate.
    • FDG-PET-CT (fluorine-18-fluorodeoxyglucose–positron-emission tomography–computed tomography) scan status at the completion of rituximab plus chemotherapy induction therapy is strongly predictive of outcome. It is not yet known if acting on the results of the scans translates into better outcomes.[44,45]


Obinutuzumab is an alternative CD20-binding monoclonal antibody with alternative epitope binding and is being studied in patients with recurrent follicular lymphoma. This agent has shown responses in 20% to 30% of patients when used alone and in 80% of patients when combined with CHOP or FC (fludarabine and cyclophosphamide) in relapsed follicular lymphoma patients.[46,47][Level of evidence: 3iiiDiv]

Purine nucleoside analogs

  • Fludarabine.[1,48,49]
  • 2-chlorodeoxyadenosine.[50,51]

Alkylating agents (with or without steroids)

  • Cyclophosphamide (oral or intravenous).[52]
  • Chlorambucil (oral).


Evidence (bendamustine):

  1. In a prospective randomized trial NCT00991211, 527 patients with indolent and mantle cell lymphoma were randomly assigned to a bendamustine-plus-rituximab arm versus an R-CHOP arm.[29][Level of evidence: 1iiDiii]
    • With a median follow-up of 45 months, the median PFS favored the bendamustine arm (69 months vs. 31 months [HR, 0.58; 95 % confidence intervaI (CI), 0.44–0.74; P < .0001]) but with no difference in OS.
    • The bendamustine arm was associated with significantly lower rates of alopecia, hematologic toxicity, stomatitis, peripheral neuropathy, and infections than was the R-CHOP arm.

Combination chemotherapy

  • CVP: cyclophosphamide + vincristine + prednisone.[1,53]
  • CVP followed by rituximab maintenance.[54]
  • C-MOPP: cyclophosphamide + vincristine + procarbazine + prednisone.[55,56]
  • CHOP: cyclophosphamide + doxorubicin + vincristine + prednisone.[52,57] A Cochrane meta-analysis could not identify any OS benefit to adding doxorubicin to chemotherapy regimens with rituximab or to chemotherapy regimens without rituximab.[37][Level of evidence: 1iiA]
  • FND: fludarabine + mitoxantrone +/- dexamethasone, as evidenced in the SWOG-9501 trial, for example.[58,59]

Yttrium-90–labeled ibritumomab tiuxetan

Yttrium-90–labeled ibritumomab tiuxetan is available for previously untreated and relapsing patients with minimal (<25%) or no marrow involvement with lymphoma (iodine-131–labeled tositumomab is no longer available because of commercial disengagement).[60-62] In a randomized, prospective trial, 554 patients with previously untreated advanced-stage follicular lymphoma received either R-CHOP times six cycles or CHOP times six cycles followed by I-131 tositumomab radioimmunotherapy (RIT); with a median follow-up of 4.9 years, there was no significant difference between the PFS and OS (2-year OS, R-CHOP, 97%; CHOP-RIT, 93%; P = .08).[63][Level of evidence: 1iiD] Because a significant prolongation of PFS was seen for R-CHOP followed by rituximab maintenance compared with R-CHOP alone,[64] this lack of benefit for CHOP-RIT was particularly disappointing. Iodine-131–labeled tositumomab became commercially unavailable in 2013.

In a randomized trial of 409 patients with stage III or IV follicular lymphoma who achieved a complete or partial response, yttrium-90 ibritumomab tiuxetan consolidation versus no consolidation was evaluated. The radiolabelled antibody consolidation improved median PFS by 3 years (P < .001), and median time to next treatment was improved by 5.1 years (P < .001); however, there was no change in OS.[65][Level of evidence: 1iiDiii]

Maintenance rituximab

Evidence (maintenance rituximab):

  1. In a prospective, randomized trial of 465 patients with relapsed follicular lymphoma, responders to R-CHOP or CHOP were further randomly assigned to rituximab maintenance (one dose every 3 months for 2 years) or no maintenance.[66][Level of evidence: 1iiDiii]
    • At 6 years' median follow-up, rituximab maintenance was better for median PFS (44 months vs. 16 months, P < .001) and borderline for 5-year OS (74% vs. 64%, P = .07).
    • This benefit for maintenance was evident even for patients who received rituximab during induction therapy. Most patients in both arms received extensive rituximab during post-protocol salvage treatment.
  2. In the PRIMA (NCT00140582) study, 1,019 high-risk patients who required treatment achieved complete or partial response after induction therapy with immunochemotherapy (usually R-CHOP) and were then randomly assigned to 2 years of maintenance rituximab versus no maintenance.[64][Level of evidence: 1iiDiii]
    • With a median follow-up of 36 months, PFS favored rituximab maintenance 74.9% to 57.6% (HR, 0.56; 95% confidence interval [CI], 0.44–0.68; P <.0001) but with no difference in OS.
  3. In a prospective, randomized trial of 280 patients with relapsed follicular lymphoma, responders to chemotherapy and autologous stem cell transplantation consolidation were randomly assigned to four doses of rituximab maintenance or no maintenance.[67][Level of evidence: 1iiDiii]
    • With an 8.3 year median follow-up, the 10-year PFS favored maintenance (54% vs. 37% [HR, 0.66; 95%CI, 0.47–0.91, P = .012]), but there was no difference in OS.
  4. A meta-analysis of 2,586 patients with follicular lymphoma in nine randomized clinical trials that compared rituximab maintenance with no maintenance showed improved OS for rituximab maintenance in previously treated patients (HRdeath, 0.72; 95% CI, 0.57–0.91).[68][Level of evidence: 1iiA]

Many questions remain about rituximab maintenance, particularly about truncating therapy at 2 years and long-term safety and efficacy. The most salient question is whether a strategy of observation after induction with rituximab therapy at time of symptomatic progression is equivalent or superior to mandated rituximab maintenance.[69]

Treatment Options Under Clinical Evaluation for Indolent, Noncontiguous Stage II/III/IV Adult NHL

Since none of the standard therapies listed above are curative for advanced-stage disease, innovative approaches are under clinical evaluation. The approaches include intensive therapy with chemotherapy and total-body irradiation (TBI) followed by autologous or allogeneic bone marrow transplantation (BMT) or peripheral stem cell transplantation (PSCT), and the use of idiotype vaccines and radiolabeled monoclonal antibodies.

  1. Intensive therapy with chemotherapy with or without TBI or high-dose radioimmunotherapy followed by autologous or allogeneic BMT or PSCT is under clinical evaluation.[70-79]
  2. Phase III trials comparing chemotherapy alone versus chemotherapy followed by anti-idiotype vaccine.[80-82]
  3. Extended-field radiation therapy (stage III patients only).[83]
  4. Ofatumumab—human anti-CD20 monoclonal antibody.[84]
  5. Short-course low-dose, palliative radiation therapy (2 × 2 Gy).[85,86]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with indolent, noncontiguous stage II adult non-Hodgkin lymphoma, indolent, stage III adult non-Hodgkin lymphoma and indolent, stage IV adult non-Hodgkin lymphoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.


  1. Hagenbeek A, Eghbali H, Monfardini S, et al.: Phase III intergroup study of fludarabine phosphate compared with cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed patients with stage III and IV low-grade malignant Non-Hodgkin's lymphoma. J Clin Oncol 24 (10): 1590-6, 2006. [PUBMED Abstract]
  2. Gribben JG: How I treat indolent lymphoma. Blood 109 (11): 4617-26, 2007. [PUBMED Abstract]
  3. Jacobs JP, Murray KJ, Schultz CJ, et al.: Central lymphatic irradiation for stage III nodular malignant lymphoma: long-term results. J Clin Oncol 11 (2): 233-8, 1993. [PUBMED Abstract]
  4. Mendenhall NP, Million RR: Comprehensive lymphatic irradiation for stage II-III non-Hodgkin's lymphoma. Am J Clin Oncol 12 (3): 190-4, 1989. [PUBMED Abstract]
  5. Smalley RV, Andersen JW, Hawkins MJ, et al.: Interferon alfa combined with cytotoxic chemotherapy for patients with non-Hodgkin's lymphoma. N Engl J Med 327 (19): 1336-41, 1992. [PUBMED Abstract]
  6. Solal-Céligny P, Lepage E, Brousse N, et al.: Doxorubicin-containing regimen with or without interferon alfa-2b for advanced follicular lymphomas: final analysis of survival and toxicity in the Groupe d'Etude des Lymphomes Folliculaires 86 Trial. J Clin Oncol 16 (7): 2332-8, 1998. [PUBMED Abstract]
  7. Andersen JW, Smalley RV: Interferon alfa plus chemotherapy for non-Hodgkin's lymphoma: five-year follow-up. N Engl J Med 329 (24): 1821-2, 1993. [PUBMED Abstract]
  8. Hagenbeek A, Carde P, Meerwaldt JH, et al.: Maintenance of remission with human recombinant interferon alfa-2a in patients with stages III and IV low-grade malignant non-Hodgkin's lymphoma. European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. J Clin Oncol 16 (1): 41-7, 1998. [PUBMED Abstract]
  9. Aviles A, Duque G, Talavera A, et al.: Interferon alpha 2b as maintenance therapy in low grade malignant lymphoma improves duration of remission and survival. Leuk Lymphoma 20 (5-6): 495-9, 1996. [PUBMED Abstract]
  10. Arranz R, García-Alfonso P, Sobrino P, et al.: Role of interferon alfa-2b in the induction and maintenance treatment of low-grade non-Hodgkin's lymphoma: results from a prospective, multicenter trial with double randomization. J Clin Oncol 16 (4): 1538-46, 1998. [PUBMED Abstract]
  11. Fisher RI, Dana BW, LeBlanc M, et al.: Interferon alpha consolidation after intensive chemotherapy does not prolong the progression-free survival of patients with low-grade non-Hodgkin's lymphoma: results of the Southwest Oncology Group randomized phase III study 8809. J Clin Oncol 18 (10): 2010-6, 2000. [PUBMED Abstract]
  12. Cole BF, Solal-Céligny P, Gelber RD, et al.: Quality-of-life-adjusted survival analysis of interferon alfa-2b treatment for advanced follicular lymphoma: an aid to clinical decision making. J Clin Oncol 16 (7): 2339-44, 1998. [PUBMED Abstract]
  13. Ozer H, Wiernik PH, Giles F, et al.: Recombinant interferon-alpha therapy in patients with follicular lymphoma. Cancer 82 (10): 1821-30, 1998. [PUBMED Abstract]
  14. Allen IE, Ross SD, Borden SP, et al.: Meta-analysis to assess the efficacy of interferon-alpha in patients with follicular non-Hodgkin's lymphoma. J Immunother 24 (1): 58-65, 2001 Jan-Feb. [PUBMED Abstract]
  15. Cheson BD: The curious case of the baffling biological. J Clin Oncol 18 (10): 2007-9, 2000. [PUBMED Abstract]
  16. Rohatiner AZ, Gregory WM, Peterson B, et al.: Meta-analysis to evaluate the role of interferon in follicular lymphoma. J Clin Oncol 23 (10): 2215-23, 2005. [PUBMED Abstract]
  17. Eek R, Falkson G: The low-grade lymphoproliferative disorders. Oncology 54 (6): 441-58, 1997 Nov-Dec. [PUBMED Abstract]
  18. Ardeshna KM, Smith P, Norton A, et al.: Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet 362 (9383): 516-22, 2003. [PUBMED Abstract]
  19. Portlock CS, Rosenberg SA: No initial therapy for stage III and IV non-Hodgkin's lymphomas of favorable histologic types. Ann Intern Med 90 (1): 10-13, 1979.
  20. Brice P, Bastion Y, Lepage E, et al.: Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires. Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol 15 (3): 1110-7, 1997. [PUBMED Abstract]
  21. Young RC, Longo DL, Glatstein E, et al.: The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. Semin Hematol 25 (2 Suppl 2): 11-6, 1988. [PUBMED Abstract]
  22. Solal-Céligny P, Bellei M, Marcheselli L, et al.: Watchful waiting in low-tumor burden follicular lymphoma in the rituximab era: results of an F2-study database. J Clin Oncol 30 (31): 3848-53, 2012. [PUBMED Abstract]
  23. Ghielmini M, Schmitz SF, Cogliatti SB, et al.: Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood 103 (12): 4416-23, 2004. [PUBMED Abstract]
  24. Witzig TE, Vukov AM, Habermann TM, et al.: Rituximab therapy for patients with newly diagnosed, advanced-stage, follicular grade I non-Hodgkin's lymphoma: a phase II trial in the North Central Cancer Treatment Group. J Clin Oncol 23 (6): 1103-8, 2005. [PUBMED Abstract]
  25. Hainsworth JD, Litchy S, Shaffer DW, et al.: Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin's lymphoma--a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 23 (6): 1088-95, 2005. [PUBMED Abstract]
  26. Williams ME: ECOG 4402: randomized phase III-trial comparing two different rituximab dosing regimens for patients with low tumor burden indolent non-Hodgkin's lymphoma. Curr Hematol Rep 3 (6): 395-6, 2004. [PUBMED Abstract]
  27. Buske C, Hiddemann W: Rituximab maintenance therapy in indolent NHL: a clinical review. Leuk Res 30 (Suppl 1): S11-5, 2006. [PUBMED Abstract]
  28. Robinson KS, Williams ME, van der Jagt RH, et al.: Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma. J Clin Oncol 26 (27): 4473-9, 2008. [PUBMED Abstract]
  29. Rummel MJ, Niederle N, Maschmeyer G, et al.: Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 381 (9873): 1203-10, 2013. [PUBMED Abstract]
  30. Flinn IW, van der Jagt R, Kahl BS, et al.: Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood 123 (19): 2944-52, 2014. [PUBMED Abstract]
  31. Czuczman MS, Koryzna A, Mohr A, et al.: Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol 23 (4): 694-704, 2005. [PUBMED Abstract]
  32. Marcus R, Imrie K, Belch A, et al.: CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 105 (4): 1417-23, 2005. [PUBMED Abstract]
  33. Marcus R, Imrie K, Solal-Celigny P, et al.: Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol 26 (28): 4579-86, 2008. [PUBMED Abstract]
  34. Czuczman MS, Weaver R, Alkuzweny B, et al.: Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol 22 (23): 4711-6, 2004. [PUBMED Abstract]
  35. Hainsworth JD, Litchy S, Morrissey LH, et al.: Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 23 (7): 1500-6, 2005. [PUBMED Abstract]
  36. Hiddemann W, Kneba M, Dreyling M, et al.: Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 106 (12): 3725-32, 2005. [PUBMED Abstract]
  37. Itchaki G, Gafter-Gvili A, Lahav M, et al.: Anthracycline-containing regimens for treatment of follicular lymphoma in adults. Cochrane Database Syst Rev 7: CD008909, 2013. [PUBMED Abstract]
  38. Zinzani PL, Pulsoni A, Perrotti A, et al.: Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and without rituximab as front-line treatment for patients with follicular lymphoma. J Clin Oncol 22 (13): 2654-61, 2004. [PUBMED Abstract]
  39. Forstpointner R, Dreyling M, Repp R, et al.: The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 104 (10): 3064-71, 2004. [PUBMED Abstract]
  40. Federico M, Luminari S, Dondi A, et al.: R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol 31 (12): 1506-13, 2013. [PUBMED Abstract]
  41. Herold M, Haas A, Srock S, et al.: Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol 25 (15): 1986-92, 2007. [PUBMED Abstract]
  42. Salles GA, Mounier N, de Guibert S, et al.: Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: final analysis of the GELA-GOELAMS FL2000 study with a 5-year follow-up. [Abstract] Blood 110 (11): A-792, 2007.
  43. Schulz H, Bohlius J, Skoetz N, et al.: Combined immunochemotherapy with rituximab improves overall survival in patients with follicular and mantle cell lymphoma: updated meta-analysis results. [Abstract] Blood 108 (11): A-2760, 2006.
  44. Dupuis J, Berriolo-Riedinger A, Julian A, et al.: Impact of [(18)F]fluorodeoxyglucose positron emission tomography response evaluation in patients with high-tumor burden follicular lymphoma treated with immunochemotherapy: a prospective study from the Groupe d'Etudes des Lymphomes de l'Adulte and GOELAMS. J Clin Oncol 30 (35): 4317-22, 2012. [PUBMED Abstract]
  45. Trotman J, Fournier M, Lamy T, et al.: Positron emission tomography-computed tomography (PET-CT) after induction therapy is highly predictive of patient outcome in follicular lymphoma: analysis of PET-CT in a subset of PRIMA trial participants. J Clin Oncol 29 (23): 3194-200, 2011. [PUBMED Abstract]
  46. Radford J, Davies A, Cartron G, et al.: Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). Blood 122 (7): 1137-43, 2013. [PUBMED Abstract]
  47. Morschhauser FA, Cartron G, Thieblemont C, et al.: Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large b-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol 31 (23): 2912-9, 2013. [PUBMED Abstract]
  48. Whelan JS, Davis CL, Rule S, et al.: Fludarabine phosphate for the treatment of low grade lymphoid malignancy. Br J Cancer 64 (1): 120-3, 1991. [PUBMED Abstract]
  49. Solal-Céligny P, Brice P, Brousse N, et al.: Phase II trial of fludarabine monophosphate as first-line treatment in patients with advanced follicular lymphoma: a multicenter study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol 14 (2): 514-9, 1996. [PUBMED Abstract]
  50. Saven A, Emanuele S, Kosty M, et al.: 2-Chlorodeoxyadenosine activity in patients with untreated, indolent non-Hodgkin's lymphoma. Blood 86 (5): 1710-6, 1995. [PUBMED Abstract]
  51. Fridrik MA, Jäger G, Kienzer HR, et al.: Efficacy and toxicity of 2-Chlorodeoxyadenosine (Cladribine)--2 h infusion for 5 days--as first-line treatment for advanced low grade non-Hodgkin's lymphoma. Eur J Cancer 34 (10): 1560-4, 1998. [PUBMED Abstract]
  52. Peterson BA, Petroni GR, Frizzera G, et al.: Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the cancer and leukemia group B. J Clin Oncol 21 (1): 5-15, 2003. [PUBMED Abstract]
  53. Hoppe RT, Kushlan P, Kaplan HS, et al.: The treatment of advanced stage favorable histology non-Hodgkin's lymphoma: a preliminary report of a randomized trial comparing single agent chemotherapy, combination chemotherapy, and whole body irradiation. Blood 58 (3): 592-8, 1981. [PUBMED Abstract]
  54. Hochster H, Weller E, Gascoyne RD, et al.: Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol 27 (10): 1607-14, 2009. [PUBMED Abstract]
  55. Anderson T, DeVita VT Jr, Simon RM, et al.: Malignant lymphoma. II Prognostic factors and response to treatment of 473 patients at the National Cancer Institute. Cancer 50 (12): 2708-21, 1982. [PUBMED Abstract]
  56. Longo DL, Young RC, Hubbard SM, et al.: Prolonged initial remission in patients with nodular mixed lymphoma. Ann Intern Med 100 (5): 651-6, 1984. [PUBMED Abstract]
  57. Dana BW, Dahlberg S, Nathwani BN, et al.: Long-term follow-up of patients with low-grade malignant lymphomas treated with doxorubicin-based chemotherapy or chemoimmunotherapy. J Clin Oncol 11 (4): 644-51, 1993. [PUBMED Abstract]
  58. Tsimberidou AM, McLaughlin P, Younes A, et al.: Fludarabine, mitoxantrone, dexamethasone (FND) compared with an alternating triple therapy (ATT) regimen in patients with stage IV indolent lymphoma. Blood 100 (13): 4351-7, 2002. [PUBMED Abstract]
  59. Velasquez WS, Lew D, Grogan TM, et al.: Combination of fludarabine and mitoxantrone in untreated stages III and IV low-grade lymphoma: S9501. J Clin Oncol 21 (10): 1996-2003, 2003. [PUBMED Abstract]
  60. Kaminski MS, Tuck M, Estes J, et al.: 131I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med 352 (5): 441-9, 2005. [PUBMED Abstract]
  61. Press OW, Unger JM, Braziel RM, et al.: Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin's lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911. J Clin Oncol 24 (25): 4143-9, 2006. [PUBMED Abstract]
  62. Scholz CW, Pinto A, Linkesch W, et al.: (90)Yttrium-ibritumomab-tiuxetan as first-line treatment for follicular lymphoma: 30 months of follow-up data from an international multicenter phase II clinical trial. J Clin Oncol 31 (3): 308-13, 2013. [PUBMED Abstract]
  63. Press OW, Unger JM, Rimsza LM, et al.: Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus (131)iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016. J Clin Oncol 31 (3): 314-20, 2013. [PUBMED Abstract]
  64. Salles G, Seymour JF, Offner F, et al.: Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet 377 (9759): 42-51, 2011. [PUBMED Abstract]
  65. Morschhauser F, Radford J, Van Hoof A, et al.: 90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the International, Randomized, Phase III First-LineIndolent trial. J Clin Oncol 31 (16): 1977-83, 2013. [PUBMED Abstract]
  66. van Oers MH, Tönnissen E, Van Glabbeke M, et al.: BCL-2/IgH polymerase chain reaction status at the end of induction treatment is not predictive for progression-free survival in relapsed/resistant follicular lymphoma: results of a prospective randomized EORTC 20981 phase III intergroup study. J Clin Oncol 28 (13): 2246-52, 2010. [PUBMED Abstract]
  67. Pettengell R, Schmitz N, Gisselbrecht C, et al.: Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol 31 (13): 1624-30, 2013. [PUBMED Abstract]
  68. Vidal L, Gafter-Gvili A, Salles G, et al.: Rituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials. J Natl Cancer Inst 103 (23): 1799-806, 2011. [PUBMED Abstract]
  69. Friedberg JW: Rituximab maintenance in follicular lymphoma: PRIMA. Lancet 377 (9759): 4-6, 2011. [PUBMED Abstract]
  70. van Besien K, Sobocinski KA, Rowlings PA, et al.: Allogeneic bone marrow transplantation for low-grade lymphoma. Blood 92 (5): 1832-6, 1998. [PUBMED Abstract]
  71. van Besien K, Loberiza FR Jr, Bajorunaite R, et al.: Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma. Blood 102 (10): 3521-9, 2003. [PUBMED Abstract]
  72. Deconinck E, Foussard C, Milpied N, et al.: High-dose therapy followed by autologous purged stem-cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by GOELAMS. Blood 105 (10): 3817-23, 2005. [PUBMED Abstract]
  73. Sebban C, Mounier N, Brousse N, et al.: Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA). Blood 108 (8): 2540-4, 2006. [PUBMED Abstract]
  74. Lenz G, Dreyling M, Schiegnitz E, et al.: Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group. Blood 104 (9): 2667-74, 2004. [PUBMED Abstract]
  75. Rohatiner AZ, Nadler L, Davies AJ, et al.: Myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma at the time of second or subsequent remission: long-term follow-up. J Clin Oncol 25 (18): 2554-9, 2007. [PUBMED Abstract]
  76. Gopal AK, Rajendran JG, Gooley TA, et al.: High-dose [131I]tositumomab (anti-CD20) radioimmunotherapy and autologous hematopoietic stem-cell transplantation for adults > or = 60 years old with relapsed or refractory B-cell lymphoma. J Clin Oncol 25 (11): 1396-402, 2007. [PUBMED Abstract]
  77. Gyan E, Foussard C, Bertrand P, et al.: High-dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS with final results after a median follow-up of 9 years. Blood 113 (5): 995-1001, 2009. [PUBMED Abstract]
  78. Al Khabori M, de Almeida JR, Guyatt GH, et al.: Autologous stem cell transplantation in follicular lymphoma: a systematic review and meta-analysis. J Natl Cancer Inst 104 (1): 18-28, 2012. [PUBMED Abstract]
  79. Schaaf M, Reiser M, Borchmann P, et al.: High-dose therapy with autologous stem cell transplantation versus chemotherapy or immuno-chemotherapy for follicular lymphoma in adults. Cochrane Database Syst Rev 1: CD007678, 2012. [PUBMED Abstract]
  80. Bendandi M, Gocke CD, Kobrin CB, et al.: Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma. Nat Med 5 (10): 1171-7, 1999. [PUBMED Abstract]
  81. Neelapu SS, Gause BL, Nikcevich DA, et al.: Phase III randomized trial of patient-specific vaccination for previously untreated patients with follicular lymphoma in first complete remission: protocol summary and interim report. Clin Lymphoma 6 (1): 61-4, 2005. [PUBMED Abstract]
  82. Inogès S, Rodrìguez-Calvillo M, Zabalegui N, et al.: Clinical benefit associated with idiotypic vaccination in patients with follicular lymphoma. J Natl Cancer Inst 98 (18): 1292-301, 2006. [PUBMED Abstract]
  83. Ha CS, Kong JS, Tucker SL, et al.: Central lymphatic irradiation for stage I-III follicular lymphoma: report from a single-institutional prospective study. Int J Radiat Oncol Biol Phys 57 (2): 316-20, 2003. [PUBMED Abstract]
  84. Czuczman MS, Fayad L, Delwail V, et al.: Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study. Blood 119 (16): 3698-704, 2012. [PUBMED Abstract]
  85. Chan EK, Fung S, Gospodarowicz M, et al.: Palliation by low-dose local radiation therapy for indolent non-Hodgkin lymphoma. Int J Radiat Oncol Biol Phys 81 (5): e781-6, 2011. [PUBMED Abstract]
  86. Rossier C, Schick U, Miralbell R, et al.: Low-dose radiotherapy in indolent lymphoma. Int J Radiat Oncol Biol Phys 81 (3): e1-6, 2011. [PUBMED Abstract]
  • Updated: February 13, 2015