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Review article: Biomedical intelligence

Vol. 141 No. 3132 (2011)

Diagnosis and treatment of follicular lymphoma

  • F Hitz
  • A Lohri
  • S Pederiva
  • K Yeow
  • S Bodis
  • E Zucca
DOI
https://doi.org/10.4414/smw.2011.13247
Cite this as:
Swiss Med Wkly. 2011;141:w13247
Published
01.08.2011

Summary

Follicular lymphoma is a slow-growing disease exhibiting a heterogeneous clinical course, with a subset of patients experiencing a rapid disease course in the first two years and some developing disease transformation to a more aggressive phenotype. The advent of highly effective therapies has resulted in an increasing number of patients who achieve long-term progression-free survival alongside a good quality of life. Monoclonal antibodies, such as rituximab, either alone or in combination with chemotherapy regimens or radioimmunotherapy have been used with significant improvements in outcome. New treatment strategies such as new antibodies, biologic agents or vaccination therapy are also under investigation for the treatment of relapsed or refractory disease, further expanding the available options for patients and physicians alike. This article presents an overview of the current therapeutic strategies for the management of follicular lymphoma, focusing on the issues encountered in clinical practice.

References

  1. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood. 1997;89:3909–18.
  2. Salles GA. Clinical features, prognosis and treatment of follicular lymphoma. Hematology. 2007:216–25.
  3. Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25:579–86.
  4. Gribben JG. How I treat indolent lymphoma. Blood. 2007;109:4617–26.
  5. Hiddemann W, Dreyling M, Stahel RA. Minimum Clinical Recommendations for diagnosis, treatment and follow-up of newly diagnosed follicular lymphoma. Ann Oncol. 2005;16 Suppl 1:i56–7.
  6. Elstrom RL, Leonard JP. FDG-PET scans in patients with lymphoma. Curr Hematol Malig Rep. 2008;3:197–203.
  7. Dreyling M. Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 Suppl 5:v181–3.
  8. Dave SS, Wright G, Tan B, et al. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med. 2004;351:2159–69.
  9. Harris NL, Swerdlow SH, Jaffe ES, et al. Follicular lymphoma. In: Swerdlow SH, Campo E, Harris NL, et al., eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC; 2008:220–6.
  10. Bosga-Bouwer AG, van den Berg A, Haralambieva E, et al. Molecular, cytogenetic, and immunophenotypic characterization of follicular lymphoma grade 3B; a separate entity or part of the spectrum of diffuse large B-cell lymphoma or follicular lymphoma? Hum Pathol. 2006;37:528–33.
  11. Piccaluga PP, Califano A, Klein U, et al. Gene expression analysis provides a potential rationale for revising the histological grading of follicular lymphomas. Haematologica. 2008;93:1033–8.
  12. Boland A, Bagust A, Hockenhull J, Davis H, Chu P, Dickson R. Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma. Health Technol Assess. 2009;13 Suppl 2:41–8.
  13. Shustik J, Quinn M, Connors JM, Gascoyne RD, Skinnider B, Sehn LH. Follicular non-Hodgkin lymphoma grades 3A and 3B have a similar outcome and appear incurable with anthracycline-based therapy. Ann Oncol. 2010;Epub ahead of print.
  14. 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.
  15. Jaffe ES, Harris NL, Stein H, Vardiman JW. World Health Organization Classification of Tumours: Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2001.
  16. Mann RB, Berard CW. Criteria for the cytologic subclassification of follicular lymphomas: a proposed alternative method. Hematol Oncol. 1983;1:187–92.
  17. Freedman AS. Biology and management of histologic transformation of indolent lymphoma. Hematology Am Soc Hematol Educ Program. 2005:314–20.
  18. Yuen AR, Kamel OW, Halpern J, Horning SJ. Long-term survival after histologic transformation of low-grade follicular lymphoma. J Clin Oncol. 1995;13:1726–33.
  19. Federico M, Vitolo U, Zinzani PL, et al. Prognosis of follicular lymphoma: a predictive model based on a retrospective analysis of 987 cases. Intergruppo Italiano Linfomi. Blood. 2000;95:783–9.
  20. Solal-Celigny P, Roy P, Colombat P, et al. Follicular lymphoma international prognostic index. Blood. 2004;104:1258–65.
  21. Gine E, Montoto S, Bosch F, et al. The Follicular Lymphoma International Prognostic Index (FLIPI) and the histological subtype are the most important factors to predict histological transformation in follicular lymphoma. Ann Oncol. 2006;17:1539–45.
  22. Keeney GE, Gooley TA, Pham RN, et al. The pretransplant Follicular Lymphoma International Prognostic Index is associated with survival of follicular lymphoma patients undergoing autologous hematopoietic stem cell transplantation. Leuk Lymphoma. 2007;48:1961–7.
  23. Montoto S, Lopez-Guillermo A, Altes A, et al. Predictive value of Follicular Lymphoma International Prognostic Index (FLIPI) in patients with follicular lymphoma at first progression. Ann Oncol. 2004;15:1484–9.
  24. Perea G, Altes A, Montoto S, et al. Prognostic indexes in follicular lymphoma: a comparison of different prognostic systems. Ann Oncol. 2005;16:1508–13.
  25. Plancarte F, Lopez-Guillermo A, Arenillas L, et al. Follicular lymphoma in early stages: high risk of relapse and usefulness of the Follicular Lymphoma International Prognostic Index to predict the outcome of patients. Eur J Haematol. 2006;76:58–63.
  26. Conconi A, Motta M, Bertoni F, et al. Patterns of survival of follicular lymphomas at a single institution through three decades. Leuk Lymphoma. 2010;51:1028–34.
  27. Federico M, Bellei M, Marcheselli L, et al. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol. 2009;27:4555–62.
  28. Federico M, Molica S, Bellei M, Luminari S. Prognostic factors in low-grade non-Hodgkin lymphomas. Curr Hematol Malig Rep. 2009;4:202–10.
  29. Gascoyne RD, Rosenwald A, Poppema S, Lenz G. Prognostic biomarkers in malignant lymphomas. Leuk Lymphoma. 2010;Epub ahead of print.
  30. Czuczman MS. Controversies in follicular lymphoma: "who, what, when, where, and why?" (not necessarily in that order!). Hematology Am Soc Hematol Educ Program. 2006:303–10.
  31. Connors JM. Induction and maintenance therapy for FL: my clinical practice. Presenation given at the International Conference on Malignant Lymphoma. 2008;Lugano, Switzerland.
  32. Feuerlein K, Zucca E, Ghielmini M. First-line treatment of follicular lymphoma: a patient-oriented algorithm. Leuk Lymphoma. 2009;50:325–34.
  33. 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. 2003;362:516–22.
  34. Ardeshna KM, Smith P, Qian W, et al. An Intergroup Randomised Trial of Rituximab Versus a Watch and Wait Strategy In Patients with Stage II, III, IV, Asymptomatic, Non-Bulky Follicular Lymphoma (Grades 1, 2 and 3a). A Preliminary Analysis. Blood 2010;ASH Annual Meeting Abstracts 116:Abstract 6.
  35. Ardeshna KM, Qian W, Stephens R, et al. Preliminary results of quality of life (QoL) analyses from the Intergroup Phase III randomised trial of rituximab vs a watch and wait approach in patients with advanced stage, asymptomatic, non-bulky follicular lymphoma. Ann Oncol. 2011;22 Suppl 4:Abstract 019.
  36. Al-Tourah AJ, Gill KK, Chhanabhai M, et al. Population-based analysis of incidence and outcome of transformed non-Hodgkin's lymphoma. J Clin Oncol. 2008;26:5165–9.
  37. Horning SJ, Rosenberg SA. The natural history of initially untreated low-grade non-Hodgkin's lymphomas. N Engl J Med. 1984;311:1471–5.
  38. Montoto S, Davies AJ, Matthews J, et al. Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma. J Clin Oncol. 2007;25:2426–33.
  39. Relander T, Johnson NA, Farinha P, Connors JM, Sehn LH, Gascoyne RD. Prognostic factors in follicular lymphoma. J Clin Oncol. 2010;28:2902–13.
  40. Martinelli G, Hsu Schmitz SF, Utiger U, et al. Long-Term Follow-Up of Patients With Follicular Lymphoma Receiving Single-Agent Rituximab at Two Different Schedules in Trial SAKK 35/98. J Clin Oncol. 2010;28:4480–4.
  41. Wilder RB, Jones D, Tucker SL, et al. Long-term results with radiotherapy for Stage I-II follicular lymphomas. Int J Radiat Oncol Biol Phys. 2001;51:1219–27.
  42. Mac Manus MP, Hoppe RT. Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University. J Clin Oncol. 1996;14:1282–90.
  43. Tezcan H, Vose JM, Bast M, Bierman PJ, Kessinger A, Armitage JO. Limited stage I and II follicular non-Hodgkin's lymphoma: the Nebraska Lymphoma Study Group experience. Leuk Lymphoma. 1999;34:273–85.
  44. Campbell BA, Voss N, Woods R, et al. Long-term outcomes for patients with limited stage follicular lymphoma: involved regional radiotherapy versus involved node radiotherapy. Cancer. 2010;116:3797–806.
  45. Advani R, Rosenberg SA, Horning SJ. Stage I and II follicular non-Hodgkin's lymphoma: long-term follow-up of no initial therapy. J Clin Oncol. 2004;22:1454–9.
  46. Haas RL, Poortmans P, de Jong D, et al. High response rates and lasting remissions after low-dose involved field radiotherapy in indolent lymphomas. J Clin Oncol. 2003;21:2474–80.
  47. De Neve WJ, Lybeert ML, Meerwaldt JH. Low-dose total body irradiation in non-Hodgkin lymphoma: short- and long-term toxicity and prognostic factor. Am J Clin Oncol. 1990;13:280–4.
  48. Lybeert ML, Meerwaldt JH, Deneve W. Long-term results of low dose total body irradiation for advanced non-Hodgkin lymphoma. Int J Radiat Oncol Biol Phys. 1987;13:1167–72.
  49. Murtha AD, Rupnow BA, Hansosn J, Knox SJ, Hoppe R. Long-term follow-up of patients with Stage III follicular lymphoma treated with primary radiotherapy at Stanford University. Int J Radiat Oncol Biol Phys. 2001;49:3–15.
  50. Fisher RI, LeBlanc M, Press OW, Maloney DG, Unger JM, Miller TP. New treatment options have changed the survival of patients with follicular lymphoma. J Clin Oncol. 2005;23:8447–52.
  51. Colombat P, Brousse N, Morschhauser F, et al. Single treatment with rituximab monotherapy for low-tumor burden follicular lymphoma (FL): survival analysis with extended follow-up (F/Up) of 7 years. Blood. 2006;ASH Annual Meeting Abstracts 108:Abstract 486.
  52. Colombat P, Salles G, Brousse N, et al. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood. 2001;97:101–6.
  53. Ghielmini M, Rufibach K, Salles G, et al. Single agent rituximab in patients with follicular or mantle cell lymphoma: clinical and biological factors that are predictive of response and event-free survival as well as the effect of rituximab on the immune system: a study of the Swiss Group for Clinical Cancer Research (SAKK). Ann Oncol. 2005;16:1675–82.
  54. 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. 2004;103:4416–23.
  55. 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. 2004;104:3064–71.
  56. 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. 2007;25:1986–92.
  57. 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. 2005;106:3725–32.
  58. Marcus R, Imrie K, Belch A, et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005;105:1417–23.
  59. Czuczman MS, Grillo-Lopez AJ, White CA, et al. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999;17:268–76.
  60. Herold M, Maschmeyer G, Lakner V, et al. Sustained survival advantage after a median follow-up of 5 years for immuno-chemotherapy (R-MCP) versus chemotherapy alone (MCP) in advanced follicular lymphoma - update of the OSHO#39 trial. Haematologica. 2010;95 (Suppl.2):Abstract 575.
  61. Rummel M, Niederle N, Maschmeyer G, et al. Bendamustine Plus Rituximab Is Superior in Respect of Progression Free Survival and CR Rate When Compared to CHOP Plus Rituximab as First-Line Treatment of Patients with Advanced Follicular, Indolent, and Mantle Cell Lymphomas: Final Results of a Randomized Phase III Study of the StiL (Study Group Indolent Lymphomas, Germany). Blood. 2009; ASH Annual Meeting Abstracts 114:Abstract 405.
  62. Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-Lopez AJ. 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. 2004;22:4711–6.
  63. Ganti AK, Weisenburger DD, Smith LM, et al. Patients with grade 3 follicular lymphoma have prolonged relapse-free survival following anthracycline-based chemotherapy: the Nebraska Lymphoma Study Group Experience. Ann Oncol. 2006;17:920–7.
  64. Rigacci L, Federico M, Martelli M, et al. The role of anthracyclines in combination chemotherapy for the treatment of follicular lymphoma: retrospective study of the Intergruppo Italiano Linfomi on 761 cases. Leuk Lymphoma. 2003;44:1911–7.
  65. Nabhan C. It is follicular.... so, why CHOP? J Clin Oncol. 2007;25:915–6; author reply 6–7.
  66. Garnock-Jones KP. Bendamustine: a review of its use in the management of indolent non-Hodgkin's lymphoma and mantle cell lymphoma. Drugs. 2010;70:1703–18.
  67. Czuczman MS, Koryzna A, Mohr A, et al. Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol. 2005;23:694–704.
  68. Schulz H, Bohlius JF, Trelle S, et al. Immunochemotherapy with rituximab and overall survival in patients with indolent or mantle cell lymphoma: a systematic review and meta-analysis. J Natl Cancer Inst. 2007;99:706–14.
  69. Aviles A, Neri N, Huerta-Guzman J, Perez F, Sotelo L. Interferon alpha 2b as maintenance therapy improves outcome in follicular lymphoma. Leuk Lymphoma. 2004;45:2247–51.
  70. Baldo P, Rupolo M, Compagnoni A, et al. Interferon-alpha for maintenance of follicular lymphoma. Cochrane Database Syst Rev. 2010;20(1):CD004629.
  71. Solal-Celigny P, Lepage E, Brousse N, et al. Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. Groupe d'Etude des Lymphomes de l'Adulte. N Engl J Med. 1993;329:1608–14.
  72. Unterhalt M, Hoster E, Dreyling M, Hiddemann W. Interferon Maintenance Prolongs Remission Duration After Rituximab-Containing Induction In First-Line Advanced Stage Follicular Lymphoma Patients – a Retrospective Analysis of the German Low-Grade Lymphoma Study Group (GLSG). Blood. 2010;ASH Annual Meeting Abstracts 116:Abstract 2864.
  73. Rohatiner AZ, Gregory WM, Peterson B, et al. Meta-analysis to evaluate the role of interferon in follicular lymphoma. J Clin Oncol. 2005;23:2215–23.
  74. van Oers MH. Rituximab maintenance therapy: a step forward in follicular lymphoma. Haematologica. 2007;92:826–33.
  75. 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. 2009;27:1607–14.
  76. van Oers MH, Klasa R, Marcus RE, et al. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006;108:3295–301.
  77. van Oers MH, Van Glabbeke M, Giurgea L, et al. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010;28:2853–8.
  78. Vidal L, Gafter-Gvili A, Leibovici L, et al. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2009;101:248–55.
  79. Salles G, Catalano J, Feugier P, et al. Rituximab maintenance for two years significantly improves the outcome of patients with untreated, high tumor burden follicular lymphoma after response to immunochemotherapy: results of the PRIMA study. Haematologica. 2010;95s:Abstract 0557.
  80. Taverna CJ, Bassi S, Hitz F, et al. First results of long-term rituximab maintenance treatment in follicular lymphoma: safety analysis of the randomized phase III trial SAKK 35/03. J Clin Oncol. 2009;27(15s):8534.
  81. Gribben JG, Neuberg D, Freedman AS, et al. Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma. Blood. 1993;81:3449–57.
  82. Morel P, Gaulard P, Gisselbrecht C, et al. Autologous stem-cell transplantation as consolidation therapy for diffuse large B-cell lymphoma patients with overexpression of bcl-2 protein. Results of the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trial LNH98–B2. Ann Oncol. 2008;19:560–5.
  83. Rohatiner AZ, Johnson PW, Price CG, et al. Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for recurrent follicular lymphoma. J Clin Oncol. 1994;12:1177–84.
  84. Hiddemann W, Buske C, Kneba M, et al. Autologous stem cell transplantation after myeloablative therapy in first remission may be beneficial in patients with advanced stage follicular lymphoma after front-line therapy with R-CHOP. An analysis of two consecutive studies of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2008;ASH Annual Meeting Abstracts 112:Abstract 772.
  85. 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. 2007;25:2554–9.
  86. 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. 2005;105:3817–23.
  87. Thieblemont C, Coiffier B. Lymphoma in older patients. J Clin Oncol. 2007;25:1916–23.
  88. Hiddemann W, Unterhalt M. Current treatment strategies in follicular lymphomas. Ann Oncol. 2006;17 Suppl 10:x155–9.
  89. Zinzani PL, Rossi G, Franceschetti S, et al. Phase II trial of short-course R-CHOP followed by 90Y-ibritumomab tiuxetan in previously untreated high-risk elderly diffuse large B-cell lymphoma patients. Clin Cancer Res. Epub ahead of print;16:3998–4004.
  90. Zinzani PL, Tani M, Pulsoni A, et al. Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ). Lancet Oncol. 2008;9:352–8.
  91. Bethge WA, Lange T, Meisner C, et al. Radioimmunotherapy with yttrium-90–ibritumomab tiuxetan as part of a reduced intensity conditioning regimen for allogeneic hematopoietic cell transplantation in patients with advanced non-Hodgkin lymphoma: results of a phase II study. Blood. 2010;116:1795–802.
  92. Delaloye AB, Antonescu C, Louton T, Kuhlmann J, Hagenbeek A. Dosimetry of 90Y-ibritumomab tiuxetan as consolidation of first remission in advanced-stage follicular lymphoma: results from the international phase 3 first-line indolent trial. J Nucl Med. 2009;50:1837–43.
  93. Morschhauser F, Radford J, Van Hoof A, et al. Phase III trial of consolidation therapy with yttrium-90–ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008;26:5156–64.
  94. Hainsworth JD, Spigel DR, Markus TM, et al. Rituximab plus short-duration chemotherapy followed by Yttrium-90 Ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma. 2009;9:223–8.
  95. Jacobs SA, Swerdlow SH, Kant J, et al. Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Clin Cancer Res. 2008;14:7088–94.
  96. Gregory SA, Hohloch K, Gisselbrecht C, Tobinai K, Dreyling M. Harnessing the energy: development of radioimmunotherapy for patients with non-Hodgkin's lymphoma. Oncologist. 2009;14 Suppl 2:4–16.
  97. Kaminski MS, Tuck M, Estes J, et al. 131I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med. 2005;352:441–9.
  98. Press OW, Unger JM, Braziel RM, et al. A phase 2 trial of CHOP chemotherapy followed by tositumomab/iodine I 131 tositumomab for previously untreated follicular non-Hodgkin lymphoma: Southwest Oncology Group Protocol S9911. Blood. 2003;102:1606–12.
  99. Witzig TE, Gordon LI, Cabanillas F, et al. Randomized controlled trial of yttrium-90–labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002;20:2453–63.
  100. Witzig TE, Flinn IW, Gordon LI, et al. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma. J Clin Oncol. 2002;20:3262–9.
  101. Horning SJ, Younes A, Jain V, et al. Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J Clin Oncol. 2005;23:712–9.
  102. Leahy MF, Turner JH. Radio-immunotherapy of indolent non-Hodgkin lymphoma with 131I-rituximab in routine clinical practice: 10–year, single institution experience of 142 consecutive patients. Blood. 2010;2010:23.
  103. Schouten HC, Qian W, Kvaloy S, et al. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol. 2003;21:3918–27.
  104. Sebban C, Brice P, Delarue R, et al. Impact of rituximab and/or high-dose therapy with autotransplant at time of relapse in patients with follicular lymphoma: a GELA study. J Clin Oncol. 2008;26:3614–20.
  105. Montoto S, Canals C, Rohatiner AZ, et al. Long-term follow-up of high-dose treatment with autologous haematopoietic progenitor cell support in 693 patients with follicular lymphoma: an EBMT registry study. Leukemia. 2007;21:2324–31.
  106. Pettengell R, Schmitz N, Gisselbrecht C, et al. Randomized study of rituximab in patients with relapsed or resistant follicular lymphoma prior to high-dose therapy as in vivo purging and to maintain remission following high-dose therapy. J Clin Oncol 2010;28(15s):Abstr. 8005.
  107. Gisselbrecht C, Bethge W, Duarte RF, et al. Current status and future perspectives for yttrium-90 ((90)Y)-ibritumomab tiuxetan in stem cell transplantation for non-Hodgkin's lymphoma. Bone Marrow Transplant. 2007;40:1007–17.
  108. van Besien K, Sobocinski KA, Rowlings PA, et al. Allogeneic bone marrow transplantation for low-grade lymphoma. Blood. 1998;92:1832–6.
  109. Khouri IF, McLaughlin P, Saliba RM, et al. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008;111:5530–6.
  110. Rezvani AR, Storer B, Maris M, et al. Nonmyeloablative allogeneic hematopoietic cell transplantation in relapsed, refractory, and transformed indolent non-Hodgkin's lymphoma. J Clin Oncol. 2008;26:211–7.
  111. Hagenbeek A, Fayad L, Delwail V, et al. Evaluation of Ofatumumab, a Novel Human CD20 Monoclonal Antibody, as Single Agent Therapy in Rituximab-Refractory Follicular Lymphoma. Blood. 2009;ASH Annual Meeting Abstracts 114:Abstract 935.
  112. Sehn LH, Assouline SE, Stewart DA, et al. A Phase I Study of GA101 (RO5072759) Monotherapy Followed by Maintenance in Patients with Multiply Relapsed/Refractory CD20+ Malignant Disease. Blood. 2009;ASH Annual Meeting Abstracts 114:Abstract 934.
  113. Sehn LH, MacDonald DA, Rubin S, et al. Bortezomib Added to CVP-R Is Safe and Effective for Previously Untreated Advanced Stage Follicular Lymphoma: A Phase II Study by the NCIC Clinical Trials Group. Blood. 2009;ASK Annual Meeting Abstracts 114:Abstract 407.
  114. Fowler N, McLaughlin P, Hagemeister F, et al. A Biologic Combination of Lenalidomide and Rituximab for Front-Line Therapy of Indolent B-Cell Non-Hodgkin's Lymphoma. Blood. 2009;ASH Annual Meeting Abstracts 114:Abstract 1714.
  115. Seam P, Juweid ME, Cheson BD. The role of FDG-PET scans in patients with lymphoma. Blood. 2007;110:3507–16.
  116. Newman JS, Francis IR, Kaminski MS, Wahl RL. Imaging of lymphoma with PET with 2–[F-18]-fluoro-2–deoxy-D-glucose: correlation with CT. Radiology. 1994;190:111–6.
  117. Stumpe KD, Urbinelli M, Steinert HC, Glanzmann C, Buck A, von Schulthess GK. Whole-body positron emission tomography using fluorodeoxyglucose for staging of lymphoma: effectiveness and comparison with computed tomography. Eur J Nucl Med. 1998;25:721–8.
  118. Thill R, Neuerburg J, Fabry U, et al. [Comparison of findings with 18–FDG PET and CT in pretherapeutic staging of malignant lymphoma]. Nuklearmedizin. 1997;36:234–9.
  119. Buchmann I, Reinhardt M, Elsner K, et al. 2–(fluorine-18)fluoro-2–deoxy-D-glucose positron emission tomography in the detection and staging of malignant lymphoma. A bicenter trial. Cancer. 2001;91:889–99.
  120. Wirth A, Seymour JF, Hicks RJ, et al. Fluorine-18 fluorodeoxyglucose positron emission tomography, gallium-67 scintigraphy, and conventional staging for Hodgkin's disease and non-Hodgkin's lymphoma. Am J Med. 2002;112:262–8.
  121. Trotman J, Fournier M, Lamy T, et al. Result of FDG PET-CT Imaging After Immunochemotherapy Induction Is a Powerful and Independent Prognostic Indicator of Outcome for Patients with Follicular Lymphoma: An Analysis From the PRIMA Study. Blood. 2010;ASH Annual Meeting Abstracts 116:Abstract 855.
  122. Horning SJ. Natural history of and therapy for the indolent non-Hodgkin's lymphomas. Semin Oncol. 1993;20:75–88.
  123. Forstpointner R, Unterhalt M, Dreyling M, et al. Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006;108:4003–8.