{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:07:21Z","timestamp":1761894441378},"reference-count":34,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Follicular lymphoma (FL) is the most common subtype of indolent lymphoma. Specific \u201cfacts\u201d about FL that were generated by past research and have been passed down as dogma to a majority of practicing oncologists over the past 20 to 30 years that need to be revisited, include: (1) do not initiate therapy soon after diagnosis in asymptomatic, advanced-stage patients since it does not change outcome; (2) initiate therapy with single-agent oral alkylators when intervention needed and \u201csave\u201d more aggressive combination chemotherapy for \u201clater\u201d since the standard chemotherapy regimen used did not seem to impact survival; (3) FL is an incurable disease and palliation of symptoms was an acceptable approach to the expected pattern of repeated relapses; (4) transformation of FL is independent of the type or timing of therapies received by a patient; (5) median overall survival (OS) for FL patients is 8\u201310 years. Although the heterogeneity of FL will never change, we are developing the scientific tools to identify and better understand the biologic and genetic features associated with its clinical variability. In the current exciting era of targeted therapies (e.g., rituximab, radioimmunoconjugates) and novel treatment approaches demonstrating an improvement in treatment outcomes (e.g., disease-free survival and OS), our old beliefs and historically accepted dogma need to be retested and revitalized. The optimal combination(s) of old and new agents and the optimal timing of when to initiate and how to sequence specific therapies will require data from well-designed clinical trials that should include important correlative laboratory studies.<\/jats:p>","DOI":"10.1182\/asheducation-2006.1.303","type":"journal-article","created":{"date-parts":[[2006,11,22]],"date-time":"2006-11-22T23:14:02Z","timestamp":1164237242000},"page":"303-310","update-policy":"http:\/\/dx.doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":15,"title":["Controversies in Follicular Lymphoma: \u201cWho, What, When, Where, and Why?\u201d (Not Necessarily in That Order!)"],"prefix":"10.1182","volume":"2006","author":[{"given":"Myron S.","family":"Czuczman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2019111704493292900_R1","doi-asserted-by":"crossref","unstructured":"Wilder RB, Jones D, Tucker SL, et al. Long-term results with radiotherapy for Stage I\u2013II follicular lymphomas. Int J Radiat Oncol Biol Phys. 2001;51:1219\u20131227.","DOI":"10.1016\/S0360-3016(01)01747-3"},{"key":"2019111704493292900_R2","doi-asserted-by":"crossref","unstructured":"Tsang RW, Gospodarowicz MK. Radiation therapy for localized low-grade non-Hodgkin\u2019s lymphomas. Hematol Oncol. 2005;23:10\u201317.","DOI":"10.1002\/hon.743"},{"key":"2019111704493292900_R3","unstructured":"Horning SJ. Natural history of and therapy for the indolent non-Hodgkin\u2019s lymphomas. Semin Oncol. 1993;20:75\u201388."},{"key":"2019111704493292900_R4","unstructured":"Young RC, Longo DL, Glatstein E, Ihde DC, Jaffe ES, DeVita VT, Jr. The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. Semin Hematol. 1988;25:11\u201316."},{"key":"2019111704493292900_R5","unstructured":"Ganti AK, Bociek RG, Bierman PJ, Enke CA, Vose JM, Armitage JO. Follicular lymphoma: expanding therapeutic options. Oncology (Williston Park). 2005;19:213\u2013228; discussion 228, 233-216, 239."},{"key":"2019111704493292900_R6","doi-asserted-by":"crossref","unstructured":"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\u2019Etude des Lymphomes Folliculaires. Groupe d\u2019Etude des Lymphomes de l\u2019Adulte. J Clin Oncol. 1997;15:1110\u20131117.","DOI":"10.1200\/JCO.1997.15.3.1110"},{"key":"2019111704493292900_R7","doi-asserted-by":"crossref","unstructured":"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\u2013522.","DOI":"10.1016\/S0140-6736(03)14110-4"},{"key":"2019111704493292900_R8","doi-asserted-by":"crossref","unstructured":"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. 2003;21:5\u201315.","DOI":"10.1200\/jco.2003.05.128"},{"key":"2019111704493292900_R9","doi-asserted-by":"crossref","unstructured":"Buckstein R, Pennell N, Berinstein NL. What is remission in follicular lymphoma and what is its relevance? Best Pract Res Clin Haematol. 2005;18:27\u201356.","DOI":"10.1016\/j.beha.2004.08.019"},{"key":"2019111704493292900_R10","unstructured":"Al-Tourah AJG; Hoskins PJ, Klasa RJ, et al. The impact of initial treatment of advanced stage indolent lymphoma on the risk of transformation [abstract]. Proc ASCO. 2006;24:7510."},{"key":"2019111704493292900_R11","doi-asserted-by":"crossref","unstructured":"Demidem A, Lam T, Alas S, Hariharan K, Hanna N, Bonavida B. Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs. Cancer Biother Radiopharm. 1997;12:177\u2013186.","DOI":"10.1089\/cbr.1997.12.177"},{"key":"2019111704493292900_R12","unstructured":"Alas S, Emmanouilides C, Bonavida B. Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin\u2019s lymphoma to apoptosis. Clin Cancer Res. 2001;7:709\u2013723."},{"key":"2019111704493292900_R13","doi-asserted-by":"crossref","unstructured":"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\u2019s lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004;22:4711\u20134716.","DOI":"10.1200\/JCO.2004.04.020"},{"key":"2019111704493292900_R14","doi-asserted-by":"crossref","unstructured":"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\u20133732.","DOI":"10.1182\/blood-2005-01-0016"},{"key":"2019111704493292900_R15","doi-asserted-by":"crossref","unstructured":"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\u20131423.","DOI":"10.1182\/blood-2004-08-3175"},{"key":"2019111704493292900_R16","doi-asserted-by":"crossref","unstructured":"Ewer MS, Martin FJ, Henderson C, Shapiro CL, Benjamin RS, Gabizon AA. Cardiac safety of liposomal anthracyclines. Semin Oncol. 2004;31:161\u2013181.","DOI":"10.1053\/j.seminoncol.2004.08.006"},{"key":"2019111704493292900_R17","doi-asserted-by":"crossref","unstructured":"Gabizon AA, Lyass O, Berry GJ, Wildgust M. Cardiac safety of pegylated liposomal doxorubicin (Doxil\/Caelyx) demonstrated by endomyocardial biopsy in patients with advanced malignancies. Cancer Invest. 2004;22:663\u2013669.","DOI":"10.1081\/CNV-200032899"},{"key":"2019111704493292900_R18","doi-asserted-by":"crossref","unstructured":"Rifkin RM, Gregory SA, Mohrbacher A, Hussein MA. Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma: a phase III multicenter randomized trial. Cancer. 2006;106:848\u2013858.","DOI":"10.1002\/cncr.21662"},{"key":"2019111704493292900_R19","doi-asserted-by":"crossref","unstructured":"Al-Batran SE, Bischoff J, von Minckwitz G, et al. The clinical benefit of pegylated liposomal doxorubicin in patients with metastatic breast cancer previously treated with conventional anthracyclines: a multicentre phase II trial. Br J Cancer. 2006;94:1615\u20131620.","DOI":"10.1038\/sj.bjc.6603158"},{"key":"2019111704493292900_R20","doi-asserted-by":"crossref","unstructured":"Czuczman MS, Skipper M, Mohr A, et al. Phase I\/II study of rituxan (R) in combination with doxil (D) in patients (pts) with relapsing or refractory B-cell lymphoma: promising early results [abstract]. Blood. 2004;104:1396a.","DOI":"10.1182\/blood.V104.11.1396.1396"},{"key":"2019111704493292900_R21","doi-asserted-by":"crossref","unstructured":"Ghielmini M, Rufibach K, Salles G, et al. Factors prognostic for response and event free survival and treatment related toxicity in 306 patients with follicular or mantle cell lymphoma randomized to single agent rituximab given at the standard or at a prolonged schedule [abstract]. Blood. 2004;104:170a.","DOI":"10.1182\/blood.V104.11.588.588"},{"key":"2019111704493292900_R22","unstructured":"Czuczman M, Grillo-Lopez A, Alkuzweny B, Weaver R, Larocca A, McLaughlin P. Prognostic factors for non-Hodgkin\u2019s lymphoma patients treated with chemotherapy may not predict outcome in patients treated with rituximab. Ann Oncol. In press."},{"key":"2019111704493292900_R23","doi-asserted-by":"crossref","unstructured":"Solal-Celigny P, Salles GA, Brousse N, et al. Single 4-dose rituximab treatment for low-tumor burden follicular lymphoma (FL): survival analyses with a follow-up (F\/Up) of at least 5 years. Blood. 2004;104:169a.","DOI":"10.1182\/blood.V104.11.585.585"},{"key":"2019111704493292900_R24","doi-asserted-by":"crossref","unstructured":"Buske C, Hoster E, Dreyling M, Hasford J, Unterhalt M, Hiddemann W. The Follicular Lymphoma International Prognostic Index (FLIPI) separates high risk from intermediate or low risk patients with advanced stage follicular lymphoma treated front-line with Rituximab and the combination of Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) with respect to treatment outcome. Blood. 2006.","DOI":"10.1182\/blood-2006-01-013367"},{"key":"2019111704493292900_R25","doi-asserted-by":"crossref","unstructured":"Gokhale AS, Mayadev J, Pohlman B, Macklis RM. Gamma camera scans and pretreatment tumor volumes as predictors of response and progression after Y-90 anti-CD20 radioimmunotherapy. Int J Radiat Oncol Biol Phys. 2005;63:194\u2013201.","DOI":"10.1016\/j.ijrobp.2005.01.017"},{"key":"2019111704493292900_R26","doi-asserted-by":"crossref","unstructured":"Kaminski MS, Zelenetz AD, Press OW, et al. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin\u2019s lymphomas. J Clin Oncol. 2001;19:3918\u20133928.","DOI":"10.1200\/JCO.2001.19.19.3918"},{"key":"2019111704493292900_R27","doi-asserted-by":"crossref","unstructured":"Dreyling M, Forstpointner R, Gramatzki M, et al. Rituximab maintenance improves progression-free and overall survival rates after combined immunochemotherapy (R-FCM) in patients with relapsed follicular and mantle cell lymphoma: Final results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol. 2006;24.","DOI":"10.1200\/jco.2006.24.18_suppl.7502"},{"key":"2019111704493292900_R28","doi-asserted-by":"crossref","unstructured":"Van Oers MHJ, Van Glabbeke M, Teodorovic I, et al. Chimeric anti-CD20 monoclonal antibody (rituximab;mabthera) in remission induction and maintenance treatment of relapsed\/resistant follicular non-Hodgkin\u2019s lymphoma: Final analysis of a Phase III randomized intergroup clinical trial. Blood. 2005;106:107a.","DOI":"10.1182\/blood.V104.11.586.586"},{"key":"2019111704493292900_R29","doi-asserted-by":"crossref","unstructured":"Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106\u2013130.","DOI":"10.3322\/canjclin.56.2.106"},{"key":"2019111704493292900_R30","doi-asserted-by":"crossref","unstructured":"Swenson WT, Wooldridge JE, Lynch CF, Forman-Hoffman VL, Chrischilles E, Link BK. Improved survival of follicular lymphoma patients in the United States. J Clin Oncol. 2005;23:5019\u20135026.","DOI":"10.1200\/JCO.2005.04.503"},{"key":"2019111704493292900_R31","doi-asserted-by":"crossref","unstructured":"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\u20138452.","DOI":"10.1200\/JCO.2005.03.1674"},{"key":"2019111704493292900_R32","doi-asserted-by":"crossref","unstructured":"Liu Q, Fayad L, Cabanillas F, et al. Improvement of overall and failure-free survival in stage IV follicular lymphoma: 25 years of treatment experience at The University of Texas M.D. Anderson Cancer Center. J Clin Oncol. 2006;24:1582\u20131589.","DOI":"10.1200\/JCO.2005.03.3696"},{"key":"2019111704493292900_R33","doi-asserted-by":"crossref","unstructured":"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\u20132169.","DOI":"10.1056\/NEJMoa041869"},{"key":"2019111704493292900_R34","doi-asserted-by":"crossref","unstructured":"Olejniczak SH, Stewart CC, Donohue K, Czuczman MS. A quantitative exploration of surface antigen expression in common B-cell malignancies using flow cytometry. Immunol Invest. 2006;35:93\u2013114.","DOI":"10.1080\/08820130500496878"}],"container-title":["Hematology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2006\/1\/303\/1091432\/303_310ash.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2006\/1\/303\/1091432\/303_310ash.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,19]],"date-time":"2020-04-19T02:30:23Z","timestamp":1587263423000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/hematology\/article\/2006\/1\/303\/19729\/Controversies-in-Follicular-Lymphoma-Who-What-When"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1,1]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,1,1]]}},"URL":"https:\/\/doi.org\/10.1182\/asheducation-2006.1.303","relation":{},"ISSN":["1520-4391","1520-4383"],"issn-type":[{"value":"1520-4391","type":"print"},{"value":"1520-4383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,1,1]]}}}