{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T20:59:11Z","timestamp":1781211551620,"version":"3.54.1"},"reference-count":49,"publisher":"American Society of Clinical Oncology (ASCO)","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Oncol Pract"],"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Philadelphia chromosome\u2013positive acute lymphoblastic leukemia accounts for approximately 20%-30% of adult acute lymphoblastic leukemia and remains associated with relapse despite imatinib-based therapy. We compared the effectiveness and safety of first-generation versus second-generation tyrosine kinase inhibitors (TKIs) in adults with newly diagnosed disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We conducted a retrospective target trial emulation using TriNetX electronic health record data from January 2014 to February 2025. Adults age 18 years or older with newly diagnosed Philadelphia chromosome\u2013positive acute lymphoblastic leukemia were eligible. After exclusions, 2,764 patients were clinically eligible; 2,295 met the as-started exposure definition for the primary comparison. Propensity score matching yielded 592 patients per arm comparing imatinib with second-generation TKIs, predominantly dasatinib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      At a median follow-up of 1,140 days for the second-generation cohort versus 1,129 days for imatinib, second-generation TKIs were associated with improved overall survival (hazard ratio, 0.677 [95% CI, 0.544 to 0.842];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001) and lower 5-year mortality (26.4%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      38.7%; risk ratio, 0.681 [95% CI, 0.576 to 0.806;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001). Findings were consistent in on-treatment and US-only analyses. Benefit was significant in patients age 18-34 and 35-64 years and with dasatinib, but not in patients age 65 years or older. Selected neurologic, hematologic, GI, and cardiometabolic toxicities were more frequent with second-generation therapy but did not offset the survival advantage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Second-generation TKIs, particularly dasatinib, may be considered as frontline therapy for many adults with newly diagnosed Philadelphia chromosome\u2013positive acute lymphoblastic leukemia, particularly those younger than 65 years.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/op-25-01316","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T19:59:11Z","timestamp":1781207951000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Target Trial Emulation of Second-Generation Versus First-Generation Tyrosine Kinase Inhibitors in Adult Philadelphia Chromosome\u2013Positive Acute Lymphoblastic Leukemia"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4043-7518","authenticated-orcid":true,"given":"Xiaoyi","family":"Zhang","sequence":"first","affiliation":[{"name":"Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3304-4643","authenticated-orcid":true,"given":"Hong-Jie","family":"Jhou","sequence":"additional","affiliation":[{"name":"Neurological Institute, Changhua Christian Hospital, Changhua, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0552-569X","authenticated-orcid":true,"given":"Hsin-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Chi Mei Medical Center, Tainan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Xiao","sequence":"additional","affiliation":[{"name":"Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0280-6417","authenticated-orcid":true,"given":"Po-Huang","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6061-5168","authenticated-orcid":true,"given":"Cho-Hao","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"e_1_3_7_2_2","first-page":"2309","article-title":"Adult Ph-positive acute lymphoblastic leukemia\u2014Current concepts in cytogenetic abnormalities and outcomes","volume":"10","author":"Shi T","year":"2020","unstructured":"Shi T, Huang X, Zhu L, et al: Adult Ph-positive acute lymphoblastic leukemia\u2014Current concepts in cytogenetic abnormalities and outcomes. Am J Cancer Res 10:2309-2318, 2020","journal-title":"Am J Cancer Res"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2011.03.002"},{"key":"e_1_3_7_4_2","volume-title":"BCR::ABL1. Leukemia","author":"Gale RP","year":"2021","unstructured":"Gale RP, Hochhaus A, Cross NCP, et al: BCR::ABL1. Leukemia, 2021. [HGNC nomenclature update]"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24137"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.21.2514"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-09-529008"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28522"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23624"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023023152"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.324"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.5868"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.4783"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.36023"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv254"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040297"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2014.07.014"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezy167"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwt212"},{"key":"e_1_3_7_20_2","first-page":"1","article-title":"Unsuitable underlying causes of death for assessing the quality of cause-of-death reporting","volume":"69","author":"Flagg LA","year":"2021","unstructured":"Flagg LA, Anderson RN: Unsuitable underlying causes of death for assessing the quality of cause-of-death reporting. Natl Vital Stat Rep 69:1-25, 2021","journal-title":"Natl Vital Stat Rep"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6004"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000002636"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03325249"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/2290120"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0302-8"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwr183"},{"key":"e_1_3_7_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2022.08.016"},{"key":"e_1_3_7_28_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-10-532341"},{"key":"e_1_3_7_29_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-636548"},{"key":"e_1_3_7_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-018-3323-8"},{"key":"e_1_3_7_31_2","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2021.0042"},{"key":"e_1_3_7_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26764"},{"key":"e_1_3_7_33_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.049759"},{"key":"e_1_3_7_34_2","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2014.0009"},{"key":"e_1_3_7_35_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-02-700153"},{"key":"e_1_3_7_36_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.76.7228"},{"key":"e_1_3_7_37_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-02-140665"},{"key":"e_1_3_7_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8722-2-46"},{"key":"e_1_3_7_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2018.01.004"},{"key":"e_1_3_7_40_2","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2024.0007"},{"key":"e_1_3_7_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2021.05.009"},{"key":"e_1_3_7_42_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2016272"},{"key":"e_1_3_7_43_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2113347"},{"key":"e_1_3_7_44_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01075"},{"key":"e_1_3_7_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34710"},{"key":"e_1_3_7_46_2","first-page":"e0256801","article-title":"Association of MRD with clinical outcomes in Ph+ ALL in the TKI era","volume":"16","author":"Zhang W","year":"2021","unstructured":"Zhang W, Jang E: Association of MRD with clinical outcomes in Ph+ ALL in the TKI era. PLoS One 16:e0256801, 2021","journal-title":"PLoS One"},{"key":"e_1_3_7_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.33529"},{"key":"e_1_3_7_48_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2022.2398"},{"key":"e_1_3_7_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15642"},{"key":"e_1_3_7_50_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019001329"}],"container-title":["JCO Oncology Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/OP-25-01316","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T19:59:13Z","timestamp":1781207953000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/OP-25-01316"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,11]]},"references-count":49,"alternative-id":["10.1200\/OP-25-01316"],"URL":"https:\/\/doi.org\/10.1200\/op-25-01316","relation":{},"ISSN":["2688-1527","2688-1535"],"issn-type":[{"value":"2688-1527","type":"print"},{"value":"2688-1535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,11]]},"assertion":[{"value":"2025-12-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-27","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"OP-25-01316"}}