{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:58:32Z","timestamp":1779911912333,"version":"3.53.1"},"reference-count":55,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,22]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Advanced phases of Philadelphia chromosome\u2013positive chronic myeloid leukemia (CML), classically encompassing de novo presentation of accelerated-phase disease and blast-phase disease (myeloid and lymphoid \u201cblast crisis\u201d) and progression to these from antecedent chronic-phase disease, have diminished in incidence but remain a challenge. Despite continued development of additional and novel kinase inhibitors of BCR::ABL1, global limitations on access to diagnostics and therapy persist and account for continued incidence of advanced disease at initial presentation and progressive disease. Evolution in defining risk through clinical and molecular characterization should increase ability to identify emerging advanced disease, minimize progression, and improve treatment of resistant chronic-phase and blast-phase diseases. While BCR::ABL1 tyrosine kinase inhibition remains central in advanced disease, combination therapy with conventional and novel chemotherapy, immunotherapy, and allogeneic stem cell transplant provide best long-term outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024026510","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T21:51:29Z","timestamp":1764712289000},"page":"369-378","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":2,"title":["How I treat advanced phases of CML"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2251-4032","authenticated-orcid":false,"given":"Michael J.","family":"Mauro","sequence":"first","affiliation":[{"name":"Chronic Myeloid Leukemia Program, Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"24","key":"2026012211221500800_bib1","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1200\/JCO.2015.66.2866","article-title":"Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population","volume":"34","author":"Bower","year":"2016","journal-title":"J Clin Oncol"},{"issue":"6","key":"2026012211221500800_bib2","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1038\/leu.2015.73","article-title":"The EUTOS population-based registry: incidence and clinical characteristics of 2904 CML patients in 20 European countries","volume":"29","author":"Hoffmann","year":"2015","journal-title":"Leukemia"},{"issue":"1","key":"2026012211221500800_bib3","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1182\/hematology.2019000050","article-title":"Meeting the needs of CML patients in resource-poor countries","volume":"2019","author":"Malhotra","year":"2019","journal-title":"Hematol Am Soc Hematol Educ Program"},{"key":"2026012211221500800_bib4","unstructured":"The Max Foundation. Accessed 9 December 2025. www.themaxfoundation.org."},{"key":"2026012211221500800_bib5","unstructured":"International Chronic Myeloid Leukemia Foundation. Accessed 9 December 2025. www.cml-foundation.org."},{"issue":"4","key":"2026012211221500800_bib6","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":"3","key":"2026012211221500800_bib7","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":"2026012211221500800_bib8","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"},{"issue":"11","key":"2026012211221500800_bib9","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1038\/s41375-023-02048-y","article-title":"European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia","volume":"37","author":"Cross","year":"2023","journal-title":"Leukemia"},{"issue":"8","key":"2026012211221500800_bib10","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","volume":"34","author":"Hehlmann","year":"2020","journal-title":"Leukemia"},{"issue":"19","key":"2026012211221500800_bib11","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1182\/blood-2017-07-792143","article-title":"Clonal chromosomal abnormalities appearing in Philadelphia chromosome\u2013negative metaphases during CML treatment","volume":"130","author":"Issa","year":"2017","journal-title":"Blood"},{"issue":"8","key":"2026012211221500800_bib12","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1038\/s41375-019-0512-y","article-title":"Laying the foundation for genomically-based risk assessment in chronic myeloid leukemia","volume":"33","author":"Branford","year":"2019","journal-title":"Leukemia"},{"issue":"9","key":"2026012211221500800_bib13","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1182\/blood-2018-02-832253","article-title":"Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high-risk disease","volume":"132","author":"Branford","year":"2018","journal-title":"Blood"},{"issue":"18","key":"2026012211221500800_bib14","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1182\/bloodadvances.2017006825","article-title":"ASXL1 and BIM germ line variants predict response and identify CML patients with the greatest risk of imatinib failure","volume":"1","author":"Marum","year":"2017","journal-title":"Blood Adv"},{"issue":"suppl 1","key":"2026012211221500800_bib15","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1182\/blood-2024-199899","article-title":"Strong association between cancer gene variants at diagnosis, especially ASXL1, and emergence of kinase domain mutation-driven resistance in CML patients despite frontline treatment with more potent BCR::ABL1 inhibitors [abstract]","volume":"144","author":"Shanmuganathan","year":"2024","journal-title":"Blood"},{"issue":"4","key":"2026012211221500800_bib16","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/cyto.b.21250","article-title":"Detection of small abnormal B-lymphoblast populations at diagnosis of chronic myelogenous leukemia, BCR-ABL1+: incidence, phenotypic features, and clinical implications","volume":"92","author":"Vrotsos","year":"2017","journal-title":"Cytometry B Clin Cytom"},{"issue":"7","key":"2026012211221500800_bib17","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic\/dendritic neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"issue":"8","key":"2026012211221500800_bib18","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1073\/pnas.0510423103","article-title":"Gene expression changes associated with progression and response in chronic myeloid leukemia","volume":"103","author":"Radich","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"2026012211221500800_bib19","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.3324\/haematol.2022.281878","article-title":"Molecular response in newly diagnosed chronic-phase chronic myeloid leukemia: prediction modeling and pathway analysis","volume":"108","author":"Radich","year":"2023","journal-title":"Haematologica"},{"issue":"8378","key":"2026012211221500800_bib20","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/S0140-6736(84)92179-2","article-title":"Allogeneic bone-marrow transplantation for chronic myelogenous leukaemia","volume":"1","author":"Speck","year":"1984","journal-title":"Lancet"},{"issue":"7","key":"2026012211221500800_bib21","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1002\/1097-0142(19880401)61:7<1441::AID-CNCR2820610727>3.0.CO;2-C","article-title":"Characteristics of accelerated disease in chronic myelogenous leukemia","volume":"61","author":"Kantarjian","year":"1988","journal-title":"Cancer"},{"issue":"6","key":"2026012211221500800_bib22","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1182\/blood-2013-05-501569","article-title":"European LeukemiaNet recommendations for the management of chronic myeloid leukemia","volume":"122","author":"Baccarani","year":"2013","journal-title":"Blood"},{"issue":"20","key":"2026012211221500800_bib23","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"issue":"11","key":"2026012211221500800_bib24","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1182\/blood.2022015850","article-title":"International Consensus Classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data","volume":"140","author":"Arber","year":"2022","journal-title":"Blood"},{"key":"2026012211221500800_bib25","doi-asserted-by":"crossref","first-page":"152303","DOI":"10.1016\/j.anndiagpath.2024.152303","article-title":"Does presence of complex translocations involving BCR::ABL1 in chronic myeloid leukemia affect the response rate to tyrosine kinase inhibitors? A systematic review of the literature","volume":"71","author":"Sharma","year":"2024","journal-title":"Ann Diagn Pathol"},{"issue":"5","key":"2026012211221500800_bib26","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/s41375-018-0341-4","article-title":"The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia: an international overview","volume":"33","author":"Baccarani","year":"2019","journal-title":"Leukemia"},{"issue":"11","key":"2026012211221500800_bib27","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1182\/blood-2009-02-204693","article-title":"Chronic myeloid leukemia (CML) with P190 BCR-ABL: analysis of characteristics, outcomes, and prognostic significance","volume":"114","author":"Verma","year":"2009","journal-title":"Blood"},{"issue":"7","key":"2026012211221500800_bib28","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1038\/s41375-020-01082-4","article-title":"Characterization of p190-Bcr-Abl chronic myeloid leukemia reveals specific signaling pathways and therapeutic targets","volume":"35","author":"Adnan-Awad","year":"2021","journal-title":"Leukemia"},{"issue":"2","key":"2026012211221500800_bib29","doi-asserted-by":"crossref","first-page":"e121","DOI":"10.1016\/S2352-3026(21)00370-7","article-title":"Ponatinib with fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor chemotherapy for patients with blast-phase chronic myeloid leukaemia (MATCHPOINT): a single-arm, multicentre, phase 1\/2 trial","volume":"9","author":"Copland","year":"2022","journal-title":"Lancet Haematol"},{"issue":"11","key":"2026012211221500800_bib30","doi-asserted-by":"crossref","first-page":"e839","DOI":"10.1016\/S2352-3026(24)00250-3","article-title":"Decitabine, venetoclax, and ponatinib for advanced phase chronic myeloid leukaemia and Philadelphia chromosome-positive acute myeloid leukaemia: a single-arm, single-centre phase 2 trial","volume":"11","author":"Short","year":"2024","journal-title":"Lancet Haematol"},{"key":"2026012211221500800_bib31","doi-asserted-by":"crossref","first-page":"217688","DOI":"10.1016\/j.canlet.2025.217688","article-title":"CAR T-Cell therapy in chronic myeloid leukemia patients with lymphoid blast crisis: a multicenter clinical analysis","volume":"621","author":"Liu","year":"2025","journal-title":"Cancer Lett"},{"issue":"15","key":"2026012211221500800_bib32","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1002\/cncr.33539","article-title":"Outcome of patients with chronic myeloid leukemia in lymphoid blastic phase and Philadelphia chromosome-positive acute lymphoblastic leukemia treated with hyper-CVAD and dasatinib","volume":"127","author":"Morita","year":"2021","journal-title":"Cancer"},{"issue":"23","key":"2026012211221500800_bib33","doi-asserted-by":"crossref","first-page":"3650","DOI":"10.1002\/cncr.30231","article-title":"Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a propensity score analysis","volume":"122","author":"Sasaki","year":"2016","journal-title":"Cancer"},{"issue":"3","key":"2026012211221500800_bib34","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/sj.leu.2404115","article-title":"High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia","volume":"20","author":"Rea","year":"2006","journal-title":"Leukemia"},{"issue":"6","key":"2026012211221500800_bib35","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1182\/blood-2016-02-700153","article-title":"Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome\u2013positive ALL","volume":"128","author":"Rousselot","year":"2016","journal-title":"Blood"},{"key":"2026012211221500800_bib36","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S1470-2045(18)30011-1","article-title":"Inotuzumab ozogamicin in combination with low-intensity chemotherapy for older patients with Philadelphia chromosome-negative acute lymphoblastic leukaemia: a single-arm, phase 2 study","volume":"19","author":"Kantarjian","year":"2018","journal-title":"Lancet Oncol"},{"issue":"6","key":"2026012211221500800_bib37","doi-asserted-by":"crossref","first-page":"e433","DOI":"10.1016\/S2352-3026(23)00073-X","article-title":"Mini-hyper-CVD plus inotuzumab ozogamicin, with or without blinatumomab, in the subgroup of older patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: long-term results of an open-label phase 2 trial","volume":"10","author":"Jabbour","year":"2023","journal-title":"Lancet Haematol"},{"issue":"25","key":"2026012211221500800_bib38","doi-asserted-by":"crossref","first-page":"6521","DOI":"10.1182\/blood-2011-05-351403","article-title":"Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia","volume":"118","author":"Fo\u00e0","year":"2011","journal-title":"Blood"},{"issue":"24","key":"2026012211221500800_bib39","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1056\/NEJMoa1902328","article-title":"Asciminib in chronic myeloid leukemia after ABL kinase inhibitor failure","volume":"381","author":"Hughes","year":"2019","journal-title":"N Engl J Med"},{"issue":"5","key":"2026012211221500800_bib40","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1038\/s41375-025-02592-9","article-title":"Asciminib in combination with imatinib, nilotinib, or dasatinib in patients with chronic myeloid leukemia in chronic or accelerated phase: phase 1 study final results","volume":"39","author":"Cortes","year":"2025","journal-title":"Leukemia"},{"issue":"6","key":"2026012211221500800_bib41","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1182\/blood.2024025800","article-title":"Asciminib plus dasatinib and prednisone for Philadelphia chromosome-positive acute leukemia","volume":"145","author":"Luskin","year":"2025","journal-title":"Blood"},{"issue":"4","key":"2026012211221500800_bib42","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ccell.2019.08.004","article-title":"Combining the allosteric inhibitor asciminib with ponatinib suppresses emergence of and restores efficacy against highly resistant BCR-ABL1 mutants","volume":"36","author":"Eide","year":"2019","journal-title":"Cancer Cell"},{"issue":"1","key":"2026012211221500800_bib43","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1001\/jamaoncol.2024.5157","article-title":"Olverembatinib after failure of tyrosine kinase inhibitors, including ponatinib or asciminib: a phase 1b randomized clinical trial","volume":"11","author":"Jabbour","year":"2025","journal-title":"JAMA Oncol"},{"issue":"5","key":"2026012211221500800_bib44","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/s41375-024-02204-y","article-title":"Management and outcome of patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era - analysis of the European LeukemiaNet blast phase registry","volume":"38","author":"Brioli","year":"2024","journal-title":"Leukemia"},{"issue":"15","key":"2026012211221500800_bib45","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1002\/cncr.30558","article-title":"Overall survival with ponatinib versus allogeneic stem cell transplantation in Philadelphia chromosome-positive leukemias with the T315I mutation","volume":"123","author":"Nicolini","year":"2017","journal-title":"Cancer"},{"issue":"7","key":"2026012211221500800_bib46","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1182\/blood-2006-04-019836","article-title":"Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia","volume":"109","author":"Carpenter","year":"2007","journal-title":"Blood"},{"issue":"9","key":"2026012211221500800_bib47","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1182\/blood-2017-03-771121","article-title":"Posttransplant feasibility study of nilotinib prophylaxis for high-risk Philadelphia chromosome positive leukemia","volume":"130","author":"Carpenter","year":"2017","journal-title":"Blood"},{"issue":"3","key":"2026012211221500800_bib48","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.bbmt.2019.10.017","article-title":"Maintenance tyrosine kinase inhibitors following allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia: a Center for International Blood and Marrow Transplant research study","volume":"26","author":"DeFilipp","year":"2020","journal-title":"Biol Blood Marrow Transpl"},{"issue":"3","key":"2026012211221500800_bib49","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41375-023-01822-2","article-title":"Management of children and adolescents with chronic myeloid leukemia in blast phase: international pediatric CML expert panel recommendations","volume":"37","author":"Sembill","year":"2023","journal-title":"Leukemia"},{"issue":"10","key":"2026012211221500800_bib50","doi-asserted-by":"crossref","first-page":"3530","DOI":"10.1182\/blood.V99.10.3530","article-title":"Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study","volume":"99","author":"Sawyers","year":"2002","journal-title":"Blood"},{"issue":"12","key":"2026012211221500800_bib51","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1038\/leu.2008.221","article-title":"Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase","volume":"22","author":"Cortes","year":"2008","journal-title":"Leukemia"},{"issue":"5","key":"2026012211221500800_bib52","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/leu.2011.355","article-title":"Nilotinib is effective in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blastic phase","volume":"26","author":"Giles","year":"2012","journal-title":"Leukemia"},{"issue":"9","key":"2026012211221500800_bib53","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1002\/ajh.24034","article-title":"Long-term efficacy and safety of bosutinib in patients with advanced leukemia following resistance\/intolerance to imatinib and other tyrosine kinase inhibitors","volume":"90","author":"Gambacorti-Passerini","year":"2015","journal-title":"Am J Hematol"},{"issue":"19","key":"2026012211221500800_bib54","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1056\/NEJMoa1306494","article-title":"A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias","volume":"369","author":"Cortes","year":"2013","journal-title":"N Engl J Med"},{"issue":"11","key":"2026012211221500800_bib55","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1002\/ajh.27073","article-title":"Risk of progression in chronic phase-chronic myeloid leukemia patients eligible for tyrosine kinase inhibitor discontinuation: Final analysis of the TFR-PRO study","volume":"98","author":"Zambrotta","year":"2023","journal-title":"Am J Hematol"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/147\/4\/369\/2497679\/blood_bld-2024-026510-c-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/147\/4\/369\/2497679\/blood_bld-2024-026510-c-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T16:22:26Z","timestamp":1769098946000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/147\/4\/369\/556836\/How-I-treat-advanced-phases-of-CML"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":55,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,1,22]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2024026510","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1,22]]},"published":{"date-parts":[[2026,1,22]]}}}