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Confirming these results in a large cohort of patients with longer follow\u2010up would establish this regimen as a new standard of care. Adults with newly diagnosed Ph\u2010positive ALL were treated with the hyper\u2010CVAD regimen. Ponatinib was added as 45\u2009mg daily\u2009\u00d7\u200914 during induction, then 45\u2009mg daily continuously (first 37 patients) or 30\u2009mg daily continuously, with dose reduction to 15\u2009mg daily upon achievement of a complete molecular response (CMR; absence of a detectable\n                      <jats:italic>BCR::ABL1<\/jats:italic>\n                      transcript by quantitative reverse transcription polymerase\u2010chain reaction at a sensitivity of 0.01%). Maintenance therapy consisted of daily ponatinib and vincristine\u2010prednisone monthly for 2\u2009years, followed by daily ponatinib indefinitely. Twelve intrathecal injections of cytarabine alternating with methotrexate were given as central nervous system prophylaxis. The trial is registered on\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link>\n                      with the identifier NCT01424982. Eighty\u2010six patients were treated. Their median age was 46\u2009years (range, 21\u201380). All 68 patients with active disease at the initiation of therapy achieved complete response (CR) The cumulative CMR rate was 86%. Twenty\u2010 patients (23%) underwent allogeneic SCT. With a median follow\u2010up of 80\u2009months (range, 16\u2013129\u2009months), the estimated 6\u2010year event\u2010free survival rate was 65% and the overall survival rate was 75%. There was no difference in outcome by performance of allogeneic SCT in first CR. Common grade 3\u20135 adverse events included infection (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u200980, 93%), increased liver transaminases (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u200926, 31%) and total bilirubin (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u200913, 15%), hypertension (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u200915, 17%), pancreatitis (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u200913, 15%), hemorrhage (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u200912, 13%), and skin rash (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u20099, 10%). Two ponatinib\u2010related deaths from myocardial infarction (3%; at months 2.6 and 4.3, respectively; both in CR) in the first 37 patients treated led to the ponatinib dose\u2010modifications mentioned earlier, with no further ponatinib\u2010related deaths observed. The long\u2010term results of ponatinib and hyper\u2010CVAD continue to demonstrate excellent outcome results and acceptable safety data, indicating that this strategy is another standard of care approach in frontline Ph\u2010positive ALL.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ajh.26816","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T02:05:55Z","timestamp":1672884355000},"page":"493-501","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Frontline combination of ponatinib and\n                    <scp>hyper\u2010CVAD<\/scp>\n                    in Philadelphia chromosome\u2010positive acute lymphoblastic leukemia: 80\u2010months follow\u2010up results"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-3307","authenticated-orcid":false,"given":"Hagop","family":"Kantarjian","sequence":"first","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2983-2738","authenticated-orcid":false,"given":"Nicholas J.","family":"Short","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitin","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of 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