{"doi":"10.1002/ajh.27708","title":"Adult Acute Lymphoblastic Leukemia: 2025 Update on Diagnosis, Therapy, and Monitoring","abstract":"DISEASE OVERVIEW: Acute lymphoblastic leukemia (ALL) is a disease of lymphoid progenitor cells arising in the bone marrow and extramedullary sites. 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 2-3 years, resulting in long-term survival in 80%-90% in pediatric patients compared to 40%-50% in adult patients, depending upon patient- and disease-specific characteristics. PHILADELPHIA CHROMOSOME-POSITIVE B-CELL ALL: Historically considered a poor risk ALL subtype, the treatment and outcome of Philadelphia chromosome (Ph)-positive B-cell 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-year 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). PHILADELPHIA CHROMOSOME-NEGATIVE B-CELL ALL: The treatment approach for patients with Ph-negative B-cell ALL was historically composed of a chemotherapy backbone (either pediatric-inspired, or Hyper-CVAD 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-term outcomes. While differences in long-term survival rates differ between age groups, such as adolescents and young adults compared to older adults (≥ 60 years), with these immunotherapy-chemotherapy regimens, the 4-year survival rates have improved to 80%-85% among patients who are able to receive these treatments. Elderly patients represent a difficult population to treat due to poor chemotherapy tolerance, high-risk disease features, and increased risk of developing therapy-related myeloid neoplasms. The use of inotuzumab ozogamicin and blinatumomab in lieu of intensive chemotherapy in this population has improved safety and efficacy in patients ≥ 60 years old. Clinical trials incorporating chimeric antigen receptor (CAR) T-cell therapy into treatment for older patients are in progress. T-CELL ALL: Combination chemotherapy regimens incorporating pegylated asparaginase and nelarabine are the standard for patients with T-cell ALL. Early T-cell precursor (ETP) ALL is a high-risk subgroup for which allogeneic SCT should be considered. Inclusion of the BCL-2 inhibitor venetoclax into treatment for patients with ETP-ALL may be beneficial and is currently being investigated. SALVAGE THERAPY: Several therapies are approved as single agents in the salvage setting. However, the best outcomes are obtained with combination therapy including chemo- and immuno- therapies followed by CAR T-cell consolidation and allogeneic SCT. Clinical trials optimizing this approach are ongoing.","journal":"American Journal of Hematology","year":2025,"id":509095,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9287,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":230404,"name":"Elias Jabbour","orcid":"0000-0003-4465-6119","position":1,"is_corresponding":false},{"id":109598,"name":"Hagop M. Kantarjian","orcid":"0000-0002-1908-3307","position":0,"is_corresponding":true}],"reference_count":225,"raw_metadata":null,"created_at":"2026-07-19T02:47:00.188082Z","pmid":"40377367","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}