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Although pediatric\u2010inspired regimens have improved outcomes in younger adults with Philadelphia chromosome (Ph)\u2010negative ALL, survival in older patients remains poor, with high rates of treatment\u2010related toxicity, early death, and relapse. Age\u2010related comorbidities, impaired organ function, and unfavorable cytogenetic and molecular features, including low hypodiploidy and TP53 mutations, further compromise prognosis. In this context, monoclonal antibodies such as blinatumomab and inotuzumab ozogamicin (InO), used alone or in combination with reduced\u2010intensity chemotherapy, have emerged as promising frontline approaches capable of deep remissions with improved tolerability. Moreover, CAR T\u2010cell therapy is increasingly recognized as a potentially effective strategy for relapsed\/refractory disease in selected older adults, particularly in the setting of low disease burden, with acceptable safety in carefully monitored cohorts. 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Overall, the refinement of immunotherapeutic approaches, coupled with biologically and geriatrically tailored treatment algorithms, offers the most promising avenue to improve long\u2010term outcomes for older patients with ALL.<\/jats:p>","DOI":"10.1111\/ejh.70169","type":"journal-article","created":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T23:49:22Z","timestamp":1773618562000},"page":"24-41","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ph\u2010Negative Acute Lymphoblastic Leukemia in the Older Adults: Biology, Therapeutic Strategies and Unmet Needs"],"prefix":"10.1111","volume":"117","author":[{"given":"Antonella","family":"Bruzzese","sequence":"first","affiliation":[{"name":"Hematology Unit, Department of Onco\u2010Hematology AO of Cosenza  Cosenza 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