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While it is the most common pediatric cancer, ALL is a rare disease overall, with approximately 6500 new cases diagnosed in the United States, in 2024. Current treatment relies on multiagent chemotherapy administered over 2\u20133\u2009years, resulting in long\u2010term survival in 80%\u201390% in pediatric patients compared to 40%\u201350% in adult patients, depending upon patient\u2010 and disease\u2010specific characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Philadelphia Chromosome\u2010Positive B\u2010Cell ALL<\/jats:title><jats:p>Historically considered a poor risk ALL subtype, the treatment and outcome of Philadelphia chromosome (Ph)\u2010positive B\u2010cell ALL were drastically changed with the advent of the BCR::ABL1 tyrosine kinase inhibitors (TKIs). The combination of a TKI with a backbone of multiagent chemotherapy, or more recently blinatumomab, is the mainstay of therapy, resulting in 5\u2010year survival rates of 80+%. Achieving a complete molecular remission, particularly by next generation sequencing, is an important prognostic indicator, which may identify patients who may avoid allogeneic stem cell transplantation (SCT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Philadelphia Chromosome\u2010Negative B\u2010Cell ALL<\/jats:title><jats:p>The treatment approach for patients with Ph\u2010negative B\u2010cell ALL was historically composed of a chemotherapy backbone (either pediatric\u2010inspired, or Hyper\u2010CVAD based). Novel agents including inotuzumab ozogamicin and blinatumomab are being incorporated into these regimens to improve the rates of measurable residual disease negativity and long\u2010term outcomes. While differences in long\u2010term survival rates differ between age groups, such as adolescents and young adults compared to older adults (\u2265\u200960\u2009years), with these immunotherapy\u2010chemotherapy regimens, the 4\u2010year survival rates have improved to 80%\u201385% among patients who are able to receive these treatments. Elderly patients represent a difficult population to treat due to poor chemotherapy tolerance, high\u2010risk disease features, and increased risk of developing therapy\u2010related myeloid neoplasms. The use of inotuzumab ozogamicin and blinatumomab in lieu of intensive chemotherapy in this population has improved safety and efficacy in patients \u2265\u200960\u2009years old. Clinical trials incorporating chimeric antigen receptor (CAR) T\u2010cell therapy into treatment for older patients are in progress.<\/jats:p><\/jats:sec><jats:sec><jats:title>T\u2010Cell ALL<\/jats:title><jats:p>Combination chemotherapy regimens incorporating pegylated asparaginase and nelarabine are the standard for patients with T\u2010cell ALL. Early T\u2010cell precursor (ETP) ALL is a high\u2010risk subgroup for which allogeneic SCT should be considered. Inclusion of the BCL\u20102 inhibitor venetoclax into treatment for patients with ETP\u2010ALL may be beneficial and is currently being investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Salvage Therapy<\/jats:title><jats:p>Several therapies are approved as single agents in the salvage setting. However, the best outcomes are obtained with combination therapy including chemo\u2010 and immuno\u2010 therapies followed by CAR T\u2010cell consolidation and allogeneic SCT. Clinical trials optimizing this approach are ongoing.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajh.27708","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T09:12:59Z","timestamp":1747386779000},"page":"1205-1231","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Adult Acute Lymphoblastic Leukemia: 2025 Update on\u00a0Diagnosis, Therapy, and Monitoring"],"prefix":"10.1002","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-3307","authenticated-orcid":false,"given":"Hagop","family":"Kantarjian","sequence":"first","affiliation":[{"name":"Department of Leukemia U.T. M.D. Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4465-6119","authenticated-orcid":false,"given":"Elias","family":"Jabbour","sequence":"additional","affiliation":[{"name":"Department of Leukemia U.T. 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