{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:12:22Z","timestamp":1793506342899,"version":"4.5.0"},"reference-count":32,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,2,23]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>At diagnosis of chronic-phase chronic myeloid leukemia (CML), there are conflicting data as to whether additional cytogenetic abnormalities (ACAs) beyond a standard Philadelphia (Ph) translocation confer a higher risk of subsequent disease progression. In the United Kingdom SPIRIT2 trial comparing imatinib 400 mg daily with dasatinib 100 mg daily, diagnostic karyotypes were available in 763 of the 814 patients recruited. Of these, 27 had ACAs in either\/both the original 4 major route group (trisomy 8 or 19, iso17q or a second Ph) or the 5 additional lesions recently described (trisomy 21, 3q26.2, monosomy 7\/7q\u2212, 11q23, and complex karyotypes), and their progression rate was significantly higher (22.2%) than in patients without one of these ACAs (2.2%; P &amp;lt; .001). Patients with ACAs had worse progression-free survival (PFS; hazard ratio [HR], 5.21; 95% confidence interval [CI], 2.59-10.50; P &amp;lt; .001) and freedom from progression (FFP; HR, 12.66; 95% CI, 4.95-32.37; P &amp;lt; .001) compared with patients without ACAs. No association was seen between the Sokal or European Treatment and Outcome Study long-term survival (ELTS) scores and the presence of ACAs. Univariate analysis showed that higher Sokal and ELTS scores and the presence of ACAs were associated with poorer PFS, though only ACAs and high-risk ELTS scores were associated with poorer FFP. Multivariable models identified both the Sokal\/ELTS score and ACAs as significant independent factors for PFS but only ELTS score and ACAs as significant independent factors for FFP. The data support the view that certain ACAs are predictive of disease progression independently of Sokal or ELTS scores.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020003570","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T16:33:44Z","timestamp":1614011624000},"page":"1102-1109","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":51,"title":["Additional chromosomal abnormalities at chronic myeloid leukemia diagnosis predict an increased risk of progression"],"prefix":"10.1182","volume":"5","author":[{"given":"Richard E.","family":"Clark","sequence":"first","affiliation":[{"name":"Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane F.","family":"Apperley","sequence":"additional","affiliation":[{"name":"Centre for Haematology, Imperial College, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mhairi","family":"Copland","sequence":"additional","affiliation":[{"name":"Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Cicconi","sequence":"additional","affiliation":[{"name":"Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"issue":"1","key":"2021022216333725900_B1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0165-4608(81)90054-6","article-title":"Cytogenetic follow-up in chronic myeloid leukemia","volume":"3","author":"Hartley","year":"1981","journal-title":"Cancer Genet Cytogenet"},{"issue":"3","key":"2021022216333725900_B2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/0165-4608(86)90004-X","article-title":"Cytogenetic studies in blast crisis of Ph-positive chronic granulocytic leukemia: results and prognostic evaluation in 52 patients","volume":"21","author":"Cervantes","year":"1986","journal-title":"Cancer Genet Cytogenet"},{"issue":"2","key":"2021022216333725900_B3","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1159\/000046636","article-title":"Cytogenetic and molecular genetic evolution of chronic myeloid leukemia","volume":"107","author":"Johansson","year":"2002","journal-title":"Acta Haematol"},{"issue":"3-4","key":"2021022216333725900_B4","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/0165-4608(85)90195-5","article-title":"Value of cytogenetic studies in prediction of acute phase CML","volume":"14","author":"Watmore","year":"1985","journal-title":"Cancer Genet Cytogenet"},{"issue":"1","key":"2021022216333725900_B5","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0165-4608(85)90041-X","article-title":"Karyotypic evolution in Ph-positive chronic myeloid leukemia in relation to management and disease progression","volume":"18","author":"Swolin","year":"1985","journal-title":"Cancer Genet Cytogenet"},{"issue":"1","key":"2021022216333725900_B6","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1182\/blood.V72.1.294.294","article-title":"Prognostic significance of additional cytogenetic abnormalities at diagnosis of Philadelphia chromosome-positive chronic granulocytic leukemia","volume":"72","author":"Sokal","year":"1988","journal-title":"Blood"},{"issue":"10","key":"2021022216333725900_B7","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1182\/blood-2002-09-2790","article-title":"Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy","volume":"101","author":"Cortes","year":"2003","journal-title":"Blood"},{"issue":"2","key":"2021022216333725900_B8","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1182\/blood-2003-02-0371","article-title":"Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate","volume":"103","author":"O\u2019Dwyer","year":"2004","journal-title":"Blood"},{"issue":"26","key":"2021022216333725900_B9","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1182\/bloodadvances.2017011858","article-title":"Cytogenetics-based risk prediction of blastic transformation of chronic myeloid leukemia in the era of TKI therapy","volume":"1","author":"Gong","year":"2017","journal-title":"Blood Adv"},{"issue":"26","key":"2021022216333725900_B10","doi-asserted-by":"crossref","first-page":"6760","DOI":"10.1182\/blood-2011-08-373902","article-title":"Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV","volume":"118","author":"Fabarius","year":"2011","journal-title":"Blood"},{"issue":"12","key":"2021022216333725900_B11","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1007\/s00277-015-2494-9","article-title":"Impact of unbalanced minor route versus major route karyotypes at diagnosis on prognosis of CML","volume":"94","author":"Fabarius","year":"2015","journal-title":"Ann Hematol"},{"issue":"1","key":"2021022216333725900_B12","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/ajh.24943","article-title":"Prognostic significance of additional chromosomal abnormalities at the time of diagnosis in patients with chronic myeloid leukemia treated with frontline tyrosine kinase inhibitors","volume":"93","author":"Alhuraiji","year":"2018","journal-title":"Am J Hematol"},{"issue":"11","key":"2021022216333725900_B13","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1002\/cncr.25015","article-title":"Survival outcomes for clonal evolution in chronic myeloid leukemia patients on second generation tyrosine kinase inhibitor therapy","volume":"116","author":"Verma","year":"2010","journal-title":"Cancer"},{"issue":"8","key":"2021022216333725900_B14","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1038\/s41375-020-0826-9","article-title":"High-risk additional chromosomal abnormalities at low blast counts herald death by CML [published correction appears in Leukemia. 2020;34:2823]","volume":"34","author":"Hehlmann","year":"2020","journal-title":"Leukemia"},{"issue":"4","key":"2021022216333725900_B15","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/s41375-020-0776-2","article-title":"European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia","volume":"34","author":"Hochhaus","year":"2020","journal-title":"Leukemia"},{"issue":"9","key":"2021022216333725900_B16","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.6004\/jnccn.2018.0071","article-title":"Chronic myeloid leukemia, version 1.2019, NCCN Clinical Practice Guidelines in Oncology","volume":"16","author":"Radich","year":"2018","journal-title":"J Natl Compr Canc Netw"},{"issue":"4","key":"2021022216333725900_B17","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1182\/blood.V63.4.789.789","article-title":"Prognostic discrimination in \u201cgood-risk\u201d chronic granulocytic leukemia","volume":"63","author":"Sokal","year":"1984","journal-title":"Blood"},{"issue":"11","key":"2021022216333725900_B18","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1093\/jnci\/90.11.850","article-title":"A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa","volume":"90","author":"Hasford","year":"1998","journal-title":"J Natl Cancer Inst"},{"issue":"3","key":"2021022216333725900_B19","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1182\/blood-2010-12-319038","article-title":"Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score","volume":"118","author":"Hasford","year":"2011","journal-title":"Blood"},{"issue":"1","key":"2021022216333725900_B20","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/leu.2015.261","article-title":"Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia","volume":"30","author":"Pfirrmann","year":"2016","journal-title":"Leukemia"},{"key":"2021022216333725900_B21","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/leu.2016.246","article-title":"Treatments and outcomes of 2904 chronic myeloid leukaemia patients from the EUTOS Population based registry","volume":"31","author":"Hoffmann","year":"2017","journal-title":"Leukemia"},{"issue":"8","key":"2021022216333725900_B22","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1038\/s41375-020-0931-9","article-title":"The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia","volume":"34","author":"Pfirrmann","year":"2020","journal-title":"Leukemia"},{"key":"2021022216333725900_B23","author":"O\u2019Brien","year":"2018"},{"issue":"6","key":"2021022216333725900_B24","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1109\/TAC.1974.1100705","article-title":"A new look at the statistical model identification","volume":"19","author":"Akaike","year":"1974","journal-title":"IEEE Trans Automat Contr"},{"issue":"1","key":"2021022216333725900_B25","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1093\/biomet\/69.1.239","article-title":"Partial residuals for the proportional hazards regression model","volume":"69","author":"Schoenfeld","year":"1982","journal-title":"Biometrika"},{"issue":"5","key":"2021022216333725900_B26","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1182\/blood-2002-07-2053","article-title":"Emergence of clonal cytogenetic abnormalities in Ph- cells in some CML patients in cytogenetic remission to imatinib but restoration of polyclonal hematopoiesis in the majority","volume":"101","author":"Bumm","year":"2003","journal-title":"Blood"},{"issue":"8","key":"2021022216333725900_B27","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/S0301-472X(03)00176-0","article-title":"The emergence of Ph-, trisomy -8+ cells in patients with chronic myeloid leukemia treated with imatinib mesylate","volume":"31","author":"Feldman","year":"2003","journal-title":"Exp Hematol"},{"issue":"9","key":"2021022216333725900_B28","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1002\/cncr.11729","article-title":"Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase","volume":"98","author":"Medina","year":"2003","journal-title":"Cancer"},{"issue":"8","key":"2021022216333725900_B29","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1038\/sj.leu.2403399","article-title":"Report of 34 patients with clonal chromosomal abnormalities in Philadelphia-negative cells during imatinib treatment of Philadelphia-positive chronic myeloid leukemia","volume":"18","author":"Terre","year":"2004","journal-title":"Leukemia"},{"issue":"7","key":"2021022216333725900_B30","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1002\/cncr.22936","article-title":"The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in philadelphia chromosome-negative cells","volume":"110","author":"Deininger","year":"2007","journal-title":"Cancer"},{"issue":"8","key":"2021022216333725900_B31","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1182\/blood-2007-01-070045","article-title":"Chromosomal abnormalities in Philadelphia chromosome negative metaphases appearing during imatinib mesylate therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase","volume":"110","author":"Jabbour","year":"2007","journal-title":"Blood"},{"issue":"22","key":"2021022216333725900_B32","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1182\/blood-2016-01-690230","article-title":"Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy","volume":"127","author":"Wang","year":"2016","journal-title":"Blood"}],"container-title":["Blood Advances"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/5\/4\/1102\/1800704\/advancesadv2020003570.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/5\/4\/1102\/1800704\/advancesadv2020003570.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T18:47:39Z","timestamp":1697914059000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article\/5\/4\/1102\/475242\/Additional-chromosomal-abnormalities-at-chronic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,22]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,2,23]]}},"URL":"https:\/\/doi.org\/10.1182\/bloodadvances.2020003570","relation":{},"ISSN":["2473-9529","2473-9537"],"issn-type":[{"value":"2473-9529","type":"print"},{"value":"2473-9537","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,22]]}}}