{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T20:03:49Z","timestamp":1778011429613,"version":"3.51.4"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"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":["Ann Hematol"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dasatinib is one of the second generation tyrosine kinase inhibitors (TKI) which is approved for the treatment of patients with chronic phase CML (CP-CML) both in the front line and in the second line setting. Pleural effusion (PE) is a unique toxicity associated with dasatinib use. Our aim was to study the incidence of pleural effusion in our cohort of patients who were treated with dasatinib for CP-CML and the safety upon TKI switch. A total of 390 patients were treated with dasatinib during their course of treatment for CP-CML. A total of 69 patients (17.6%) developed any grade of PE. About 33 (48%) patients developed CTCAE grade 2 PE, 34 (49%) grade 3 and only 1 patient developed grade 4 PE. Recurrence of PE was observed in 34 (49%) patients. While only 12 patients (17.3%) continued using dasatinib after development of PE, dasatinib was discontinued in the other 57 patients. Therapy was switched to bosutinib in 13 patients out of which 6 (46%) patients re-developed PE. While only 12.5% patients developed re-accumulation of pleural fluid in patients switched to imatinib, none of the patients switched to nilotinib re-developed PE. A change in TKI to bosutinib was associated with a 46% risk of recurrence of PE in patients who develop PE on dasatinib for the treatment of CP-CML. The incidence of recurrent PE was markedly lower in patient switched to imatinib or nilotinib.<\/jats:p>","DOI":"10.1007\/s00277-024-05760-6","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T07:01:56Z","timestamp":1713423716000},"page":"1941-1945","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Incidence of pleural effusion with dasatinib and the effect of switching therapy to a different TKI in patients with chronic phase CML"],"prefix":"10.1007","volume":"103","author":[{"given":"Akriti G","family":"Jain","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quinto","family":"Gesiotto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Somedeb","family":"Ball","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Nodzon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Onyee","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Padron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Kuykendall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rami","family":"Komrokji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Sallman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey E","family":"Lancet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Pinilla-Ibarz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kendra","family":"Sweet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"issue":"17","key":"5760_CR1","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1056\/NEJM199904293401706","volume":"340","author":"CL Sawyers","year":"1999","unstructured":"Sawyers CL (1999) Chronic myeloid leukemia. N Engl J Med 340(17):1330\u20131340","journal-title":"N Engl J Med"},{"issue":"5","key":"5760_CR2","doi-asserted-by":"publisher","first-page":"e186","DOI":"10.1016\/S2352-3026(15)00048-4","volume":"2","author":"K Sasaki","year":"2015","unstructured":"Sasaki K, Strom SS, O\u2019Brien S, Jabbour E, Ravandi F, Konopleva M et al (2015) Relative survival in patients with chronic-phase chronic myeloid leukaemia in the tyrosine-kinase inhibitor era: analysis of patient data from six prospective clinical trials. Lancet Haematol 2(5):e186\u2013e193","journal-title":"Lancet Haematol"},{"issue":"5682","key":"5760_CR3","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1126\/science.1099480","volume":"305","author":"NP Shah","year":"2004","unstructured":"Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL (2004) Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 305(5682):399\u2013401","journal-title":"Science"},{"issue":"11","key":"5760_CR4","doi-asserted-by":"publisher","first-page":"5790","DOI":"10.1158\/0008-5472.CAN-05-4187","volume":"66","author":"JS Tokarski","year":"2006","unstructured":"Tokarski JS, Newitt JA, Chang CY, Cheng JD, Wittekind M, Kiefer SE et al (2006) The structure of Dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants. Cancer Res 66(11):5790\u20135797","journal-title":"Cancer Res"},{"issue":"9","key":"5760_CR5","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1002\/ajh.24423","volume":"91","author":"NP Shah","year":"2016","unstructured":"Shah NP, Rousselot P, Schiffer C, Rea D, Cortes JE, Milone J et al (2016) Dasatinib in imatinib-resistant or -intolerant chronic-phase, chronic myeloid leukemia patients: 7-year follow-up of study CA180-034. Am J Hematol 91(9):869\u2013874","journal-title":"Am J Hematol"},{"issue":"2","key":"5760_CR6","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1002\/cncr.24734","volume":"116","author":"K Porkka","year":"2010","unstructured":"Porkka K, Khoury HJ, Paquette RL, Matloub Y, Sinha R, Cortes JE (2010) Dasatinib 100\u00a0mg once daily minimizes the occurrence of pleural effusion in patients with chronic myeloid leukemia in chronic phase and efficacy is unaffected in patients who develop pleural effusion. Cancer 116(2):377\u2013386","journal-title":"Cancer"},{"issue":"8","key":"5760_CR7","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1038\/leu.2009.46","volume":"23","author":"S Mustjoki","year":"2009","unstructured":"Mustjoki S, Ekblom M, Arstila TP, Dybedal I, Epling-Burnette PK, Guilhot F et al (2009) Clonal expansion of T\/NK-cells during tyrosine kinase inhibitor dasatinib therapy. Leukemia 23(8):1398\u20131405","journal-title":"Leukemia"},{"issue":"1","key":"5760_CR8","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3324\/haematol.2018.188987","volume":"104","author":"TP Hughes","year":"2019","unstructured":"Hughes TP, Laneuville P, Rousselot P, Snyder DS, Rea D, Shah NP et al (2019) Incidence, outcomes, and risk factors of pleural effusion in patients receiving dasatinib therapy for Philadelphia chromosome-positive leukemia. Haematologica 104(1):93\u2013101","journal-title":"Haematologica"},{"issue":"2","key":"5760_CR9","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.clml.2016.09.012","volume":"17","author":"JE Cortes","year":"2017","unstructured":"Cortes JE, Jimenez CA, Mauro MJ, Geyer A, Pinilla-Ibarz J, Smith BD (2017) Pleural Effusion in Dasatinib-treated patients with chronic myeloid leukemia in chronic phase: identification and management. Clin Lymphoma Myeloma Leuk 17(2):78\u201382","journal-title":"Clin Lymphoma Myeloma Leuk"},{"key":"5760_CR10","doi-asserted-by":"crossref","unstructured":"Phan C, Jutant EM, Tu L, Thuillet R, Seferian A, Montani D et al (2018) Dasatinib increases endothelial permeability leading to pleural effusion. Eur Respir J. ;51(1)","DOI":"10.1183\/13993003.01096-2017"},{"issue":"20","key":"5760_CR11","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1200\/JCO.2015.64.8899","volume":"34","author":"JE Cortes","year":"2016","unstructured":"Cortes JE, Saglio G, Kantarjian HM, Baccarani M, Mayer J, Boqu\u00e9 C et al (2016) Final 5-Year study results of DASISION: the Dasatinib Versus Imatinib Study in Treatment-Na\u00efve Chronic myeloid leukemia patients trial. J Clin Oncol 34(20):2333\u20132340","journal-title":"J Clin Oncol"},{"issue":"9","key":"5760_CR12","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1182\/blood-2013-07-513937","volume":"123","author":"HM Kantarjian","year":"2014","unstructured":"Kantarjian HM, Cortes JE, Kim DW, Khoury HJ, Br\u00fcmmendorf TH, Porkka K et al (2014) Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors. Blood 123(9):1309\u20131318","journal-title":"Blood"},{"issue":"28","key":"5760_CR13","doi-asserted-by":"publisher","first-page":"3486","DOI":"10.1200\/JCO.2011.38.7522","volume":"30","author":"JE Cortes","year":"2012","unstructured":"Cortes JE, Kim DW, Kantarjian HM, Br\u00fcmmendorf TH, Dyagil I, Griskevicius L et al (2012) Bosutinib versus Imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J Clin Oncol 30(28):3486\u20133492","journal-title":"J Clin Oncol"},{"issue":"11","key":"5760_CR14","doi-asserted-by":"publisher","first-page":"2609","DOI":"10.1007\/s00277-019-03802-y","volume":"98","author":"M Tiribelli","year":"2019","unstructured":"Tiribelli M, Abruzzese E, Capodanno I, Sor\u00e0 F, Trabacchi E, Iurlo A et al (2019) Efficacy and safety of bosutinib in chronic phase CML patients developing pleural effusion under dasatinib therapy. Ann Hematol 98(11):2609\u20132611","journal-title":"Ann Hematol"},{"issue":"25","key":"5760_CR15","doi-asserted-by":"publisher","first-page":"3908","DOI":"10.1200\/JCO.2007.12.0329","volume":"25","author":"A Quint\u00e1s-Cardama","year":"2007","unstructured":"Quint\u00e1s-Cardama A, Kantarjian H, O\u2019brien S, Borthakur G, Bruzzi J, Munden R et al (2007) Pleural effusion in patients with chronic myelogenous leukemia treated with dasatinib after imatinib failure. J Clin Oncol 25(25):3908\u20133914","journal-title":"J Clin Oncol"},{"issue":"5","key":"5760_CR16","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1111\/j.1365-2141.2008.07108.x","volume":"141","author":"H de Lavallade","year":"2008","unstructured":"de Lavallade H, Punnialingam S, Milojkovic D, Bua M, Khorashad JS, Gabriel IH et al (2008) Pleural effusions in patients with chronic myeloid leukaemia treated with dasatinib may have an immune-mediated pathogenesis. Br J Haematol 141(5):745\u2013747","journal-title":"Br J Haematol"},{"key":"5760_CR17","first-page":"85","volume":"5","author":"X Wang","year":"2013","unstructured":"Wang X, Roy A, Hochhaus A, Kantarjian HM, Chen TT, Shah NP (2013) Differential effects of dosing regimen on the safety and efficacy of dasatinib: retrospective exposure-response analysis of a phase III study. Clin Pharmacol 5:85\u201397","journal-title":"Clin Pharmacol"},{"issue":"2","key":"5760_CR18","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1111\/bjh.17654","volume":"194","author":"P Rousselot","year":"2021","unstructured":"Rousselot P, Mollica L, Guilhot J, Guerci A, Nicolini FE, Etienne G et al (2021) Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients. Br J Haematol 194(2):393\u2013402","journal-title":"Br J Haematol"},{"issue":"11","key":"5760_CR19","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1002\/ajh.26689","volume":"97","author":"E Jabbour","year":"2022","unstructured":"Jabbour E, Sasaki K, Haddad FG, Issa GC, Skinner J, Dellasala S et al (2022) Low-dose dasatinib 50\u00a0mg\/day versus standard-dose dasatinib 100\u00a0mg\/day as frontline therapy in chronic myeloid leukemia in chronic phase: a propensity score analysis. Am J Hematol 97(11):1413\u20131418","journal-title":"Am J Hematol"},{"issue":"8","key":"5760_CR20","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1038\/s41375-020-0915-9","volume":"34","author":"A Hochhaus","year":"2020","unstructured":"Hochhaus A, Gambacorti-Passerini C, Abboud C, Gjertsen BT, Br\u00fcmmendorf TH, Smith BD et al (2020) Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia: primary results of the phase 4 BYOND study. Leukemia 34(8):2125\u20132137","journal-title":"Leukemia"},{"issue":"7","key":"5760_CR21","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1038\/s41375-022-01589-y","volume":"36","author":"TH Br\u00fcmmendorf","year":"2022","unstructured":"Br\u00fcmmendorf TH, Cortes JE, Milojkovic D, Gambacorti-Passerini C, Clark RE, le Coutre P et al (2022) Bosutinib versus Imatinib for newly diagnosed chronic phase chronic myeloid leukemia: final results from the BFORE trial. Leukemia 36(7):1825\u20131833","journal-title":"Leukemia"},{"issue":"2","key":"5760_CR22","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1007\/s00277-018-3507-2","volume":"98","author":"V Garc\u00eda-Guti\u00e9rrez","year":"2019","unstructured":"Garc\u00eda-Guti\u00e9rrez V, Milojkovic D, Hernandez-Boluda JC, Claudiani S, Martin Mateos ML, Casado-Montero LF et al (2019) Safety and efficacy of bosutinib in fourth-line therapy of chronic myeloid leukemia patients. Ann Hematol 98(2):321\u2013330","journal-title":"Ann Hematol"},{"issue":"5","key":"5760_CR23","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1183\/13993003.01410-2016","volume":"48","author":"M Riou","year":"2016","unstructured":"Riou M, Seferian A, Savale L, Chaumais MC, Guignabert C, Canuet M et al (2016) Deterioration of pulmonary hypertension and pleural effusion with bosutinib following dasatinib lung toxicity. Eur Respir J 48(5):1517\u20131519","journal-title":"Eur Respir J"},{"issue":"12","key":"5760_CR24","doi-asserted-by":"publisher","first-page":"3454","DOI":"10.3324\/haematol.2022.281944","volume":"108","author":"JE Cortes","year":"2023","unstructured":"Cortes JE, Lipton JH, Kota V, Castagnetti F, Assouline S, Br\u00fcmmendorf TH et al (2023) Cross-intolerance with bosutinib after prior tyrosine kinase inhibitors for Philadelphia chromosome-positive leukemia: long-term analysis of a phase I\/II study. Haematologica 108(12):3454\u20133459","journal-title":"Haematologica"},{"key":"5760_CR25","doi-asserted-by":"crossref","unstructured":"Aslan NA, H\u0131ncal HO, Elver \u00d6, Erol V, G\u00fcler N (2022) Bosutinib-induced massive pleural effusion: cross-intolerance with all tyrosine kinase inhibitors. J Oncol Pharm Pract. :10781552221114070","DOI":"10.1177\/10781552221114070"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-024-05760-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-024-05760-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-024-05760-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T06:07:50Z","timestamp":1715580470000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-024-05760-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,18]]},"references-count":25,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["5760"],"URL":"https:\/\/doi.org\/10.1007\/s00277-024-05760-6","relation":{},"ISSN":["0939-5555","1432-0584"],"issn-type":[{"value":"0939-5555","type":"print"},{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,18]]},"assertion":[{"value":"15 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Institutional review board.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"AGJ, QG, SB, LS, AR: No conflicts of interest to declare. OC: Research Funding: Syntrix Pharmaceuticals EP: Research Funding: Bristol Myers Squibb, Syntrix Pharmaceuticals, Kura, Incyte; Honoraria: Taiho, Stemline, Blueprint AK: Research Support: Protagonist, Blueprint Medicines Corporation, GSK - Sierra Oncology, Prelude Pharmaceuticals, Bristol Myers Squibb, Morphosys; Consultancy: Imago Biosciences, Incyte, Blueprint Medicines Corporation, Novartis, Abbvie, GSK - Sierra Oncology, Bristol Myers Squibb, Pharmaessentia, CTI Biopharma; Honoraria: Imago Biosciences, Incyte, Blueprint Medicines Corporation, Novartis, Abbvie, GSK - Sierra Oncology, Bristol Myers Squibb, Pharmaessentia, CTI Biopharma; Speakers Bureau: Imago Biosciences, Incyte, Blueprint Medicines Corporation, Novartis, Abbvie, GSK - Sierra Oncology, Bristol Myers Squibb, Pharmaessentia, CTI Biopharma RK: Consultancy: Servier, AbbVie, Geron, Acceleron Pharma, Taiho Oncology, Novartis, Jazz Pharmaceuticals, Bristol Myers Squibb; Honoraria: Servier, AbbVie, CTI BioPharma, Innovent, PharmaEssentia, Takeda, Jazz Pharmaceuticals, Bristol Myers Squibb; Speakers Bureau: Servier, AbbVie, Jazz Pharmaceuticals; Advisory board: CTI BioPharma, Taiho Oncology, PharmaEssentia, Takeda, Novartis, Bristol Myers Squibb; Speakers Bureau: Bristol Myers Squibb; Research Funding: Bristol Myers Squibb. DAS: Advisory Board: Intellia, Aprea, Syndax, Bristol Myers Squibb, Nemucore, Agios, AbbVie, Kite, Shattuck Labs, Novartis; Consultancy: Takeda, Novartis, Magenta; Speakers Bureau: Bristol Myers Squibb, Incyte; Research funding: Aprea, Syntrix Pharmaceuticals; Patents & Royalties: Lixte JEL: Consultancy: Dedham Group, Jasper Therapeutics, Astellas, Dava Oncology, Novartis, Agios\/Servio, Boxer Capital, Jazz, BerGenBio, Millenium Pharma\/Takeda, ElevateBio Management, Daiichi Sankyo, AbbVie, Servier; Research Funding: Syntrix Pharmaceuticals, Celgene\/ Bristol Myers SquibbKS: Consultancy: Pfizer, Mablytics, berGenBio, Curis, Novartis, Gilead Sciences, Inc., AROG, Astellas, Bristol Myers Squibb; Advisory board: Pfizer, berGenBio, Curis, Novartis, Gilead Sciences, Inc., AROG, Astellas, Bristol Myers Squibb; Research funding: Pfizer, Syntrix Pharmaceuticals, Incyte; Honoraria: Mablytics, berGenBio, Curis, Novartis, Gilead Sciences, Inc., AROG, Astellas, Bristol Myers Squibb.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}