{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T03:22:25Z","timestamp":1793762545191,"version":"4.6.1"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T00:00:00Z","timestamp":1626480000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T00:00:00Z","timestamp":1626480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Blood Cancer J."],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immediate treatment for asymptomatic, low-tumor burden follicular lymphoma (FL) has not shown an overall survival benefit over \u201cwatch and wait\u201d (W\/W) strategy. We estimated incidence of treatment initiation at specific time points and assessed its association with the presence of any criteria such as GELF, BNLI, GITMO at diagnosis. FL patients managed by W\/W strategy were identified from the Molecular Epidemiology Resource (MER) of the University of Iowa\/Mayo Clinic Lymphoma SPORE between 2002 and 2015. Cumulative incidence estimates of treatment initiation were calculated using transformation (as the first event) and death as competing risks. 401 FL patients were identified on W\/W strategy. At a median follow-up of 8 years, 256 (64%) initiated treatment. For patients on the W\/W strategy for 5 years, the likelihood of treatment initiation in the next 5 years was 12% compared to 43% at diagnosis unlike transformation rates which remained steady. Patients with any of popular treatment criteria at diagnosis did not have increased therapy initiation rates (44% vs. 42%) during the first 5 years or lymphoma-related death rates at 10 years (6% vs. 7%). Identifying biological differences in patients with early vs. late or no progression is a critical next step in understanding outcomes in W\/W patients.<\/jats:p>","DOI":"10.1038\/s41408-021-00525-0","type":"journal-article","created":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T15:02:23Z","timestamp":1626534143000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Patterns of therapy initiation during the first decade for patients with follicular lymphoma who were observed at diagnosis in the rituximab era"],"prefix":"10.1038","volume":"11","author":[{"family":"Arushi Khurana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Mwangi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1244-6758","authenticated-orcid":false,"given":"Stephen M.","family":"Ansell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Habermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7482-178X","authenticated-orcid":false,"given":"James R.","family":"Cerhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Strouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K.","family":"Link","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1576-8341","authenticated-orcid":false,"given":"Yucai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7132-0226","authenticated-orcid":false,"given":"Rebecca L.","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Macon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2907-0809","authenticated-orcid":false,"given":"J. C.","family":"Villasboas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4215-6500","authenticated-orcid":false,"given":"Thomas E.","family":"Witzig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1867-0526","authenticated-orcid":false,"given":"Matthew J.","family":"Maurer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6955-9393","authenticated-orcid":false,"given":"Grzegorz S.","family":"Nowakowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,17]]},"reference":[{"key":"525_CR1","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/S1470-2045(14)70027-0","volume":"15","author":"KM Ardeshna","year":"2014","unstructured":"Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, et al. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014;15:424\u201335.","journal-title":"Lancet Oncol"},{"key":"525_CR2","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1111\/bjh.13895","volume":"172","author":"LJ Nastoupil","year":"2016","unstructured":"Nastoupil LJ, Sinha R, Byrtek M, Ziemiecki R, Zhou X, Taylor M, et al. Outcomes following watchful waiting for stage II-IV follicular lymphoma patients in the modern era. Br J Haematol. 2016;172:724\u201334.","journal-title":"Br J Haematol"},{"key":"525_CR3","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1111\/bjh.13316","volume":"169","author":"TC El-Galaly","year":"2015","unstructured":"El-Galaly TC, Bilgrau AE, de Nully Brown P, Mylam KJ, Ahmad SA, Pedersen LM, et al. A population-based study of prognosis in advanced stage follicular lymphoma managed by watch and wait. Br J Haematol. 2015;169:435\u201344.","journal-title":"Br J Haematol"},{"key":"525_CR4","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1200\/JCO.1997.15.3.1110","volume":"15","author":"P Brice","year":"1997","unstructured":"Brice P, Bastion Y, Lepage E, Brousse N, Ha\u00efoun C, Moreau P, 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. J Clin Oncol. 1997;15:1110\u20137.","journal-title":"J Clin Oncol."},{"key":"525_CR5","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/S0140-6736(03)14110-4","volume":"362","author":"KM Ardeshna","year":"2003","unstructured":"Ardeshna KM, Smith P, Norton A, Hancock BW, Hoskin PJ, MacLennan KA, 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\u201322.","journal-title":"Lancet"},{"key":"525_CR6","doi-asserted-by":"publisher","first-page":"3848","DOI":"10.1200\/JCO.2010.33.4474","volume":"30","author":"P Solal-C\u00e9ligny","year":"2012","unstructured":"Solal-C\u00e9ligny P, Bellei M, Marcheselli L, Pesce EA, Pileri S, McLaughlin P, et al. Watchful waiting in low-tumor burden follicular lymphoma in the rituximab era: Results of an F2-study database. J Clin Oncol. 2012;30:3848\u201353.","journal-title":"J Clin Oncol."},{"key":"525_CR7","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1200\/JCO.18.00400","volume":"37","author":"C Sarkozy","year":"2019","unstructured":"Sarkozy C, Maurer MJ, Link BK, Ghesquieres H, Nicolas E, Thompson CA, et al. Cause of death in follicular lymphoma in the first decade of the rituximab era: A pooled analysis of French and US cohorts. J Clin Oncol. 2019;37:144\u201352.","journal-title":"J Clin Oncol."},{"key":"525_CR8","doi-asserted-by":"publisher","first-page":"4480","DOI":"10.1200\/JCO.2010.28.4786","volume":"28","author":"G Martinelli","year":"2010","unstructured":"Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, 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\u20134.","journal-title":"J Clin Oncol."},{"key":"525_CR9","doi-asserted-by":"publisher","first-page":"2380","DOI":"10.1093\/annonc\/mds177","volume":"23","author":"P Colombat","year":"2012","unstructured":"Colombat P, Brousse N, Salles G, Morschhauser F, Brice P, Soubeyran P. et al. Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: Survival analyses with 7-year follow-up. Ann Oncol. 2012;23:2380\u20135.","journal-title":"Ann Oncol"},{"key":"525_CR10","doi-asserted-by":"publisher","first-page":"3272","DOI":"10.1200\/JCO.2012.48.3990","volume":"31","author":"BK Link","year":"2013","unstructured":"Link BK, Maurer MatthewJ, Nowakowski GrzegorzS, Ansell StephenM, Macon WilliamR, Syrbu SergeiI, et al. Rates and outcomes of follicular lymphoma transformation in the immunochemotherapy era: A report from the university of Iowa\/mayo clinic specialized program of research excellence molecular epidemiology resource. J Clin Oncol. 2013;31:3272\u20138.","journal-title":"J Clin Oncol"},{"key":"525_CR11","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1200\/JCO.2014.57.6801","volume":"33","author":"LynneI Wagner","year":"2015","unstructured":"Wagner LynneI, Zhao Fengmin, Hong Fangxin, Williams MichaelE, Gascoyne RandyD, Krauss JohnC, et al. Anxiety and health-related quality of life among patients with low-tumor burden non-Hodgkin lymphoma randomly assigned to two different rituximab dosing regimens: results from ECOG Trial E4402 (RESORT). J Clin Oncol. 2015;33:740\u20138.","journal-title":"J Clin Oncol."},{"key":"525_CR12","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1200\/JCO.2005.12.052","volume":"23","author":"TE Witzig","year":"2005","unstructured":"Witzig TE, Vukov AM, Habermann TM, Geyer S, Kurtin PJ, Friedenberg WR, et al. Rituximab therapy for patients with newly diagnosed, advanced-stage, follicular grade I non-Hodgkin\u2019s lymphoma: A phase II trial in the North Central Cancer Treatment Group. J Clin Oncol. 2005;23:1103\u20138.","journal-title":"J Clin Oncol."},{"key":"525_CR13","doi-asserted-by":"publisher","first-page":"2332","DOI":"10.1200\/JCO.1998.16.7.2332","volume":"16","author":"P Solal-C\u00e9ligny","year":"1998","unstructured":"Solal-C\u00e9ligny P, Lepage E, Brousse N, Tendler CL, Brice P, Ha\u00efoun C, 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\u2019etude des lymphames folliculaires 86 trial. J Clin Oncol. 1998;16:2332\u20138.","journal-title":"J Clin Oncol."},{"key":"525_CR14","doi-asserted-by":"publisher","unstructured":"Cerhan JR, Link BK, Habermann TM, Maurer MJ, Feldman AL, Syrbu SI, et al. Cohort profile: The lymphoma Specialized Program of Research Excellence (SPORE) Molecular Epidemiology Resource (MER) cohort study, Int. J. Epidemiol. 46;2017, https:\/\/doi.org\/10.1093\/ije\/dyx119.","DOI":"10.1093\/ije\/dyx119"},{"key":"525_CR15","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1200\/JCO.2008.18.1495","volume":"27","author":"BK Link","year":"2009","unstructured":"Link BK, Friedberg JW, Taylor MD, Cerhan JR, Flowers CR, Dillon H, et al. Follicular lymphoma in the United States: first report of the national LymphoCare study. J Clin Oncol. 2009;27:1202\u20138.","journal-title":"J Clin Oncol."},{"key":"525_CR16","doi-asserted-by":"publisher","first-page":"3121","DOI":"10.1200\/JCO.2005.05.1003","volume":"24","author":"TM Habermann","year":"2006","unstructured":"Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24:3121\u20137.","journal-title":"J Clin Oncol."},{"key":"525_CR17","unstructured":"\u201cShiny.\u201d https:\/\/shiny.rstudio.com\/. (Accessed 1 May 2020)."},{"key":"525_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-020-00340-z","volume":"10","author":"CL Batlevi","year":"2020","unstructured":"Batlevi CL, Sha F, Alperovich A, Ni A, Smith K, Ying Z, et al. Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups. Blood Cancer J. 2020;10:74 https:\/\/doi.org\/10.1038\/s41408-020-00340-z. no. 7","journal-title":"Blood Cancer J"},{"key":"525_CR19","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1158\/1078-0432.CCR-07-1254","volume":"14","author":"MS Czuczman","year":"2008","unstructured":"Czuczman MS, Olejniczak S, Gowda A, Kotowski A, Binder A, Kaur H, et al. Acquirement of rituximab resistance in lymphoma cell lines is associated with both global CD20 gene and protein down-regulation regulated at the pretranscriptional and posttranscriptional levels. Clin Cancer Res. 2008;14:1561\u201370.","journal-title":"Clin Cancer Res."},{"key":"525_CR20","doi-asserted-by":"publisher","first-page":"4885","DOI":"10.1182\/blood-2008-08-175208","volume":"113","author":"J Hiraga","year":"2009","unstructured":"Hiraga J, Tomita A, Sugimoto T, Shimada K, Ito M, Nakamura S, et al. Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: Its prevalence and clinical significance. Blood. 2009;113:4885\u201393.","journal-title":"Blood"},{"key":"525_CR21","doi-asserted-by":"publisher","first-page":"4981","DOI":"10.1182\/blood.V118.21.4981.4981","volume":"118","author":"L Mozessohn","year":"2011","unstructured":"Mozessohn L, Cheung M, Crump M, Buckstein R, Berinstein NL, Imrie KR, et al. Rituximab resistant follicular lymphoma: predictors of rituximab resistance, incidence of transformation and prognosis. Blood. 2011;118:4981.","journal-title":"Blood"},{"key":"525_CR22","doi-asserted-by":"crossref","unstructured":"Brian K. Link, Bann-Mo Day, Xiaolei Zhou, Andrew D. Zelenetz, Keith L. Dawson, James R. Cerhan et al., Second-line and subsequent therapy and outcomes for follicular lymphoma in the United States: data from the observational National LymphoCare Study. Br J Haematol. 2019;184:660\u20133.","DOI":"10.1111\/bjh.15149"},{"key":"525_CR23","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/S1470-2045(20)30442-3","volume":"21","author":"L Lee","year":"2020","unstructured":"Lee L, Cazier JB, Starkey T, Briggs S, Arnold R, Bisht V, et al. COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study. Lancet Oncol. 2020;21:1309\u201316.","journal-title":"Lancet Oncol"},{"key":"525_CR24","doi-asserted-by":"publisher","first-page":"2881","DOI":"10.1182\/blood.2020008824","volume":"136","author":"Abi Vijenthira","year":"2020","unstructured":"Vijenthira Abi, Gong InnaY, Fox ThomasA, Booth Stephen, Cook Gordon, Fattizzo Bruno, et al. Outcomes of patients with hematologic malignancies and COVID-19: A systematic review and meta-analysis of 3377 patients. Blood. 2020;136:2881\u201392.","journal-title":"Blood"},{"key":"525_CR25","unstructured":"COVID-19 and Indolent Lymphomas\u2014Hematology.org. https:\/\/www.hematology.org\/covid-19\/covid-19-and-indolent-lymphomas. (Accessed 19 Dec 2020)."},{"key":"525_CR26","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1182\/blood-2015-01-621375","volume":"126","author":"ND Wagner-Johnston","year":"2015","unstructured":"Wagner-Johnston ND, Link BK, Byrtek M, Dawson KL, Hainsworth J, Flowers CR, et al. Outcomes of transformed follicular lymphoma in the modern era: A report from the National LymphoCare Study (NLCS). Blood. 2015;126:851\u20137.","journal-title":"Blood"},{"key":"525_CR27","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/S1470-2045(15)00169-2","volume":"16","author":"A Pastore","year":"2015","unstructured":"Pastore A, Jurinovic V, Kridel R, Hoster E, Staiger AM, Szczepanowski M, et al. Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry. Lancet Oncol. 2015;16:1111\u201322.","journal-title":"Lancet Oncol"},{"key":"525_CR28","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/S1470-2045(14)70066-X","volume":"15","author":"SM Ansell","year":"2014","unstructured":"Ansell SM. Follicular lymphoma: Watch and wawatch and worry. Lancet Oncol. 2014;15:368\u20139.","journal-title":"Lancet Oncol"},{"key":"525_CR29","doi-asserted-by":"publisher","first-page":"e251","DOI":"10.1016\/S1470-2045(14)70215-3","volume":"15","author":"T LeBlanc","year":"2014","unstructured":"LeBlanc T, Kamal A, Abernethy A. Rituximab for follicular lymphoma: Watch and wait, watch and worry, or watch and live?. Lancet Oncol. 2014;15:e251\u20132.","journal-title":"Lancet Oncol"},{"key":"525_CR30","doi-asserted-by":"publisher","first-page":"3096","DOI":"10.1200\/JCO.2014.56.5853","volume":"32","author":"BS Kahl","year":"2014","unstructured":"Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, et al. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: Eastern cooperative oncology group protocol E4402. J Clin Oncol. 2014;32:3096\u2013102.","journal-title":"J Clin Oncol."},{"issue":"Feb","key":"525_CR31","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1001\/jamainternmed.2013.1874","volume":"173","author":"J Yoong","year":"2013","unstructured":"Yoong J, Park ER, Greer JA, Jackson VA, Gallagher ER, Pirl WF, et al. Early palliative care in advanced lung cancer: a qualitative study. JAMA Intern Med. 2013;173(Feb):283\u201390.","journal-title":"JAMA Intern Med."}],"container-title":["Blood Cancer Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41408-021-00525-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41408-021-00525-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41408-021-00525-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T18:21:46Z","timestamp":1669918906000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41408-021-00525-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,17]]},"references-count":31,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["525"],"URL":"https:\/\/doi.org\/10.1038\/s41408-021-00525-0","relation":{},"ISSN":["2044-5385"],"issn-type":[{"value":"2044-5385","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,17]]},"assertion":[{"value":"11 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"133"}}