{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T15:08:09Z","timestamp":1776092889361,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematology Reports"],"abstract":"<jats:p>Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) remains a high-risk entity despite advances in tyrosine kinase inhibitors (TKIs), immunotherapy, and cellular therapies. Relapse driven by clonal evolution, central nervous system (CNS) sanctuary disease, and TKI resistance, particularly T315I mutations, continues to limit durable disease control. Asciminib, a first-in-class allosteric BCR::ABL1 (STAMP) inhibitor, has demonstrated efficacy and favorable tolerability in chronic myeloid leukemia, but its optimal role in Ph+ ALL remains to be defined. We report a three-patient case series of Ph+ acute leukemia treated with asciminib across diverse high-risk clinical settings, including multiply relapsed disease, CNS involvement, T315I-mutated leukemia, post-CAR-T-cell relapses, and transplant bridging. Clinical outcomes are contextualized through a comprehensive review of emerging clinical trial data, real-world cohorts, and mechanistic studies evaluating asciminib in Ph+ ALL. Across all cases, asciminib was incorporated as part of combination or consolidation strategies rather than as monotherapy in active disease. Asciminib contributed to molecular disease control, CNS leukemia clearance, and successful bridging to allogeneic transplantation or cellular therapy, with acceptable tolerability and no major vascular toxicity. Integration of published evidence demonstrates that asciminib exhibits consistent biological activity in Ph+ ALL, with improved durability when used in rational combinations, particularly with immunotherapy or ATP-competitive TKIs. Preclinical data further support asciminib\u2019s compatibility with antibody-based and cellular therapies through preservation of immune effector function. Asciminib represents a versatile but context-dependent therapeutic option in Ph+ ALL. Its greatest clinical value appears to lie in rational combination regimens, maintenance strategies, and bridging to definitive therapies rather than single-agent salvage. Emerging structural biomarkers and ongoing clinical trials are expected to further refine patient selection, sequencing, and optimal integration of asciminib, particularly in CNS-involved disease and post-CAR-T cell relapse.<\/jats:p>","DOI":"10.3390\/hematolrep18020028","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T14:10:48Z","timestamp":1776089448000},"page":"28","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Asciminib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Case Series and Review of Emerging Evidence"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8123-8405","authenticated-orcid":false,"given":"Mostafa F.","family":"Mohammed Saleh","sequence":"first","affiliation":[{"name":"Adult Hematology, Transplantation and Cellular Therapy Department, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"},{"name":"Clinical Hematology Unit, Department of Internal Medicine, Faculty of Medicine, Assiut University, Assiut 71515, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9401-810X","authenticated-orcid":false,"given":"Abdulrahman","family":"Nasiri","sequence":"additional","affiliation":[{"name":"College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh 13318, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed Kotb","family":"Abdrabou","sequence":"additional","affiliation":[{"name":"Adult Hematology, Transplantation and Cellular Therapy Department, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"},{"name":"Clinical Hematology Unit, Internal Medicine Department, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadeel","family":"Samarkandi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Cancer Centre of Excellence, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0003-0130","authenticated-orcid":false,"given":"Ayman","family":"Saad","sequence":"additional","affiliation":[{"name":"Adult Hematology, Transplantation and Cellular Therapy Department, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud","family":"Aljurf","sequence":"additional","affiliation":[{"name":"Adult Hematology, Transplantation and Cellular Therapy Department, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2105-1048","authenticated-orcid":false,"given":"Amr","family":"Hanbali","sequence":"additional","affiliation":[{"name":"Adult Hematology, Transplantation and Cellular Therapy Department, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Alahmari","sequence":"additional","affiliation":[{"name":"Adult Hematology, Transplantation and Cellular Therapy Department, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1056\/NEJMra2113347","article-title":"Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia","volume":"386","author":"Chiaretti","year":"2022","journal-title":"N. 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