{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:28:45Z","timestamp":1792024125389,"version":"4.4.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum der Ruhr-Universit\u00e4t Bochum"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recently, there has been increased concern about a risk of secondary malignancies (SM) occurring in myelofibrosis (MF) patients receiving ruxolitinib (RUX). In polycythemia vera (PV), on the other hand, only limited data on the risk of SM under RUX treatment are available. To investigate the association between RUX therapy in PV and SM, we conducted a retrospective, single-center study that included 289 PV patients. RUX was administered to 32.9% (95\/289) of patients for a median treatment duration of 48.0\u00a0months (range 1.0\u2013101.6). Within a median follow-up of 97\u00a0months (1.0\u2013395.0) after PV diagnosis, 24 SM occurred. Comparing the number of PV patients with RUX-associated SM (<jats:italic>n<\/jats:italic>\u2009=\u200910, 41.7%) with the 14 (58.3%) patients who developed SM without RUX, no significant difference (<jats:italic>p<\/jats:italic>\u2009=\u20090.34, chi square test) was found. No increased incidences of melanoma, lymphoma, or solid \u201cnon-skin\u201d malignancies were observed with RUX (<jats:italic>p<\/jats:italic>\u2009=\u20090.31, <jats:italic>p<\/jats:italic>\u2009=\u20090.60, and <jats:italic>p<\/jats:italic>\u2009=\u20090.63, respectively, chi square test). However, significantly more NMSC occurred in association with RUX treatment (<jats:italic>p<\/jats:italic>\u2009=\u20090.03, chi-squared test). The \u201cSM-free survival\u201d was not significantly different by log rank test for all 289 patients (<jats:italic>p<\/jats:italic>\u2009=\u20090.65), for the patients (<jats:italic>n<\/jats:italic>\u2009=\u2009208; 72%) receiving cytoreductive therapy (<jats:italic>p<\/jats:italic>\u2009=\u20090.48) or for different therapy sequences (<jats:italic>p<\/jats:italic>\u2009=\u20090.074). In multivariate analysis, advanced age at PV diagnosis (HR 1.062 [95% CI 1.028, 1.098]) but not administration of RUX (HR 1.068 [95% CI 0.468, 2.463]) was associated with an increased risk for SM (<jats:italic>p<\/jats:italic>\u2009=\u20090.005). According to this retrospective analysis, no increased risk of SM due to RUX treatment could be substantiated for PV.<\/jats:p>","DOI":"10.1007\/s00277-021-04647-0","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T03:43:16Z","timestamp":1630381396000},"page":"2707-2716","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Ruxolitinib-treated polycythemia vera patients and their risk of secondary malignancies"],"prefix":"10.1007","volume":"100","author":[{"given":"Rohit","family":"Sekhri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parvis","family":"Sadjadian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Kolatzki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlo","family":"Huenerbein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Meixner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Marchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Wallmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Griesshammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7682-8563","authenticated-orcid":false,"given":"Kai","family":"Wille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"4647_CR1","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1182\/blood-2009-03-209262","volume":"114","author":"JW Vardiman","year":"2009","unstructured":"Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A et al (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114:937\u2013951. https:\/\/doi.org\/10.1182\/blood-2009-03-209262","journal-title":"Blood"},{"key":"4647_CR2","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.1182\/blood-2014-07-591610","volume":"124","author":"T Barbui","year":"2014","unstructured":"Barbui T, Carobbio A, Rumi E, Finazzi G, Gisslinger H, Rodeghiero F et al (2014) In contemporary patients with polycythemia vera, rates of thrombosis and risk factors delineate a new clinical epidemiology. Blood 124:3021\u20133023. https:\/\/doi.org\/10.1182\/blood-2014-07-591610","journal-title":"Blood"},{"key":"4647_CR3","doi-asserted-by":"publisher","first-page":"3383","DOI":"10.1182\/blood-2007-11-121434","volume":"111","author":"F Passamonti","year":"2008","unstructured":"Passamonti F, Rumi E, Caramella M, Elena C, Arcaini L, Boveri E et al (2008) A dynamic prognostic model to predict survival in post-polycythemia vera myelofibrosis. Blood 111:3383\u20133387. https:\/\/doi.org\/10.1182\/blood-2007-11-121434","journal-title":"Blood"},{"key":"4647_CR4","doi-asserted-by":"publisher","first-page":"2664","DOI":"10.1182\/blood-2004-09-3426","volume":"105","author":"G Finazzi","year":"2005","unstructured":"Finazzi G, Caruso V, Marchioli R, Capnist G, Chisesi T, Finelli C et al (2005) Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study. Blood 105:2664\u20132670. https:\/\/doi.org\/10.1182\/blood-2004-09-3426","journal-title":"Blood"},{"key":"4647_CR5","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1002\/ajh.25700","volume":"95","author":"M Marchetti","year":"2020","unstructured":"Marchetti M, Ghirardi A, Masciulli A, Carobbio A, Palandri F, Vianelli N et al (2020) Second cancers in MPN: survival analysis from an international study. Am J Hematol 95:295\u2013301. https:\/\/doi.org\/10.1002\/ajh.25700","journal-title":"Am J Hematol"},{"key":"4647_CR6","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.3109\/10428194.2015.1071490","volume":"57","author":"AM Brunner","year":"2016","unstructured":"Brunner AM, Hobbs G, Jalbut MM, Neuberg DS, Fathi AT (2016) A population-based analysis of second malignancies among patients with myeloproliferative neoplasms in the SEER database. Leuk Lymphoma 57:1197\u20131200. https:\/\/doi.org\/10.3109\/10428194.2015.1071490","journal-title":"Leuk Lymphoma"},{"key":"4647_CR7","doi-asserted-by":"publisher","first-page":"237","DOI":"10.3109\/10428194.2015.1041392","volume":"57","author":"L Masarova","year":"2016","unstructured":"Masarova L, Cherry M, Newberry KJ, Estrov Z, Cortes JE, Kantarjian HM, Verstovsek S (2016) Secondary solid tumors and lymphoma in patients with essential thrombocythemia and polycythemia vera \u2014 single center experience. Leuk Lymphoma 57:237\u2013239. https:\/\/doi.org\/10.3109\/10428194.2015.1041392","journal-title":"Leuk Lymphoma"},{"key":"4647_CR8","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41408-017-0038-3","volume":"8","author":"A Ghirardi","year":"2018","unstructured":"Ghirardi A, Carobbio A, Masciulli A, Barbui T (2018) Incidence of solid tumors in polycythemia vera treated with phlebotomy with or without hydroxyurea: ECLAP follow-up data. Blood Cancer J 8:5. https:\/\/doi.org\/10.1038\/s41408-017-0038-3","journal-title":"Blood Cancer J"},{"key":"4647_CR9","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1056\/NEJMoa1409002","volume":"372","author":"AM Vannucchi","year":"2015","unstructured":"Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F et al (2015) Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med 372:426\u2013435. https:\/\/doi.org\/10.1056\/NEJMoa1409002","journal-title":"N Engl J Med"},{"key":"4647_CR10","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/S1470-2045(16)30558-7","volume":"18","author":"F Passamonti","year":"2017","unstructured":"Passamonti F, Griesshammer M, Palandri F, Egyed M, Benevolo G, Devos T et al (2017) Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study. Lancet Oncol 18:88\u201399. https:\/\/doi.org\/10.1016\/S1470-2045(16)30558-7","journal-title":"Lancet Oncol"},{"key":"4647_CR11","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1182\/blood-2017-10-810739","volume":"132","author":"E Porpaczy","year":"2018","unstructured":"Porpaczy E, Tripolt S, Hoelbl-Kovacic A, Gisslinger B, Bago-Horvath Z, Casanova-Hevia E et al (2018) Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1\/2 inhibitor therapy. Blood 132:694\u2013706. https:\/\/doi.org\/10.1182\/blood-2017-10-810739","journal-title":"Blood"},{"key":"4647_CR12","doi-asserted-by":"publisher","first-page":"4089","DOI":"10.1002\/cam4.2107","volume":"8","author":"B Mora","year":"2019","unstructured":"Mora B, Rumi E, Guglielmelli P, Barraco D, Maffioli M, Rambaldi A et al (2019) Second primary malignancies in postpolycythemia vera and postessential thrombocythemia myelofibrosis: a study on 2233 patients. Cancer Med 8:4089\u20134092. https:\/\/doi.org\/10.1002\/cam4.2107","journal-title":"Cancer Med"},{"key":"4647_CR13","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1038\/leu.2016.148","volume":"30","author":"CN Harrison","year":"2016","unstructured":"Harrison CN, Vannucchi AM, Kiladjian J-J, Al-Ali HK, Gisslinger H, Knoops L et al (2016) Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia 30:1701\u20131707. https:\/\/doi.org\/10.1038\/leu.2016.148","journal-title":"Leukemia"},{"key":"4647_CR14","doi-asserted-by":"publisher","first-page":"3196","DOI":"10.1182\/bloodadvances.2019000646","volume":"3","author":"M Maffioli","year":"2019","unstructured":"Maffioli M, Giorgino T, Mora B, Iurlo A, Elli E, Finazzi MC et al (2019) Second primary malignancies in ruxolitinib-treated myelofibrosis: real-world evidence from 219 consecutive patients. Blood Adv 3:3196\u20133200. https:\/\/doi.org\/10.1182\/bloodadvances.2019000646","journal-title":"Blood Adv"},{"key":"4647_CR15","doi-asserted-by":"publisher","first-page":"1996","DOI":"10.1038\/s41375-019-0487-8","volume":"33","author":"T Barbui","year":"2019","unstructured":"Barbui T, Ghirardi A, Masciulli A, Carobbio A, Palandri F, Vianelli N et al (2019) Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study Leukemia 33:1996\u20132005. https:\/\/doi.org\/10.1038\/s41375-019-0487-8","journal-title":"A nested case-control study Leukemia"},{"key":"4647_CR16","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41408-018-0054-y","volume":"8","author":"T Barbui","year":"2018","unstructured":"Barbui T, Thiele J, Gisslinger H, Kvasnicka HM, Vannucchi AM, Guglielmelli P et al (2018) The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J 8:15. https:\/\/doi.org\/10.1038\/s41408-018-0054-y","journal-title":"Blood Cancer J"},{"key":"4647_CR17","unstructured":"Onkopedia. Polycythaemia Vera (PV). April 2019. https:\/\/www.onkopedia.com\/de\/onkopedia\/guidelines\/polycythaemia-vera-pv\/@@guideline\/html\/index.html#litID0ELRAG. Accessed 31 Jan 2021."},{"key":"4647_CR18","doi-asserted-by":"publisher","first-page":"1874","DOI":"10.1038\/leu.2013.163","volume":"27","author":"A Tefferi","year":"2013","unstructured":"Tefferi A, Rumi E, Finazzi G, Gisslinger H, Vannucchi AM, Rodeghiero F et al (2013) Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia 27:1874\u20131881. https:\/\/doi.org\/10.1038\/leu.2013.163","journal-title":"Leukemia"},{"key":"4647_CR19","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1111\/j.1365-2141.2009.08019.x","volume":"148","author":"G Barosi","year":"2010","unstructured":"Barosi G, Birgegard G, Finazzi G, Griesshammer M, Harrison C, Hasselbalch H et al (2010) A unified definition of clinical resistance and intolerance to hydroxycarbamide in polycythaemia vera and primary myelofibrosis: results of a European LeukemiaNet (ELN) consensus process. Br J Haematol 148:961\u2013963. https:\/\/doi.org\/10.1111\/j.1365-2141.2009.08019.x","journal-title":"Br J Haematol"},{"key":"4647_CR20","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/sj.leu.2404473","volume":"21","author":"G Barosi","year":"2007","unstructured":"Barosi G, Besses C, Birgegard G, Briere J, Cervantes F, Finazzi G et al (2007) A unified definition of clinical resistance\/intolerance to hydroxyurea in essential thrombocythemia: results of a consensus process by an international working group. Leukemia 21:277\u2013280. https:\/\/doi.org\/10.1038\/sj.leu.2404473","journal-title":"Leukemia"},{"key":"4647_CR21","doi-asserted-by":"publisher","first-page":"E185","DOI":"10.1002\/ajh.25489","volume":"94","author":"E Rumi","year":"2019","unstructured":"Rumi E, Zibellini S, Boveri E, Cavalloni C, Riboni R, Casetti IC et al (2019) Ruxolitinib treatment and risk of B-cell lymphomas in myeloproliferative neoplasms. Am J Hematol 94:E185\u2013E188. https:\/\/doi.org\/10.1002\/ajh.25489","journal-title":"Am J Hematol"},{"key":"4647_CR22","doi-asserted-by":"crossref","unstructured":"Pemmaraju N, Kantarjian H, Nastoupil L, Dupuis M, Zhou L, Pierce S, et al. Characteristics of patients with myeloproliferative neoplasms with lymphoma, with or without JAK inhibitor therapy; 2019 May 23.","DOI":"10.1182\/blood-2019-01-897637"},{"key":"4647_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0945-3","author":"F Stegelmann","year":"2020","unstructured":"Stegelmann F, Wille K, Busen H et al (2020) Significant association of cutaneous adverse events with hydroxyurea: results from a prospective non-interventional study in BCR-ABL1-negative myeloproliferative neoplasms (MPN) - on behalf of the German Study Group-MPN. Leukemia. https:\/\/doi.org\/10.1038\/s41375-020-0945-3","journal-title":"Leukemia"},{"issue":"3","key":"4647_CR24","doi-asserted-by":"publisher","first-page":"e226","DOI":"10.1016\/S2352-3026(19)30207-8","volume":"7","author":"JJ Kiladjian","year":"2020","unstructured":"Kiladjian JJ, Zachee P, Hino M et al (2020) Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol 7(3):e226\u2013e237. https:\/\/doi.org\/10.1016\/S2352-3026(19)30207-8","journal-title":"Lancet Haematol"},{"key":"4647_CR25","doi-asserted-by":"crossref","unstructured":"Passamonti F, Palandri F, Saydam, G, et al. 2020 Long-term effect of ruxolitinib (RUX) in inadequately controlled polycythemia vera (PV) without splenomegaly: 5-year results from the phase 3 response-2 study. Paper presented at: 62nd ASH Annual Meeting; December 5\u20138.","DOI":"10.1182\/blood-2020-139281"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-021-04647-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-021-04647-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-021-04647-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T01:56:11Z","timestamp":1634090171000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-021-04647-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,31]]},"references-count":25,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["4647"],"URL":"https:\/\/doi.org\/10.1007\/s00277-021-04647-0","relation":{},"ISSN":["0939-5555","1432-0584"],"issn-type":[{"value":"0939-5555","type":"print"},{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,31]]},"assertion":[{"value":"21 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The questionnaire and study protocol for this retrospective study were approved by the Ethics Committee of the Ruhr-Universit\u00e4t Bochum, based in Bad Oeynhausen (Protocol file number #2020\u2013704)<i>.<\/i>","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Patients gave informed consent regarding publication of their data.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Martin Griesshammer: <u>Speaker\u00b4s bureau and Advisory Board: Amgen, AOP, Orphan, Novartis, Celgene, CTI, Shire, Pfizer, Roche, Janssen, Gilead, Astra Zeneca.<\/u>Kai Wille: <u>Advisory Boards and Congress fees: Amgen, Pfizer, Roche, Janssen, Novartis, BMS, Gilead, Shire.<\/u>All other authors declare that they have no conflict of interest or competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}