T Acute Lymphoblastic Leukemia

Bispecific antibodies such as blinatumomab (anti-CD19), antibody-drug conjugates like inotuzumab ozogamicin (anti-CD22), and monoclonal antibodies such as daratumumab (anti-CD38) have demonstrated efficacy in relapsed or refractory disease with improved safety profiles. The integration of targeted and immune-based therapies into conventional regimens represents a decisive step toward precision medicine, aiming to enhance survival outcomes while reducing treatment-related toxicity and improving quality of life in ALL children. This review aims to provide a comprehensive overview of the current understanding of ALL pathobiology and therapeutic approaches, with particular emphasis on the expanding role of immunotherapeutic strategies in pediatric disease.

Universal BE-CAR7 T cells induced leukemic remission in patients with relapsed or refractory T-cell ALL, thus allowing successful allogeneic hematopoietic stem-cell transplantation in most of the patients. (Funded by the Medical Research Council and others; ISRCTN Registry number, ISRCTN15323014.).

Collectively, these ncRNAs integrate into the complex regulatory circuits of KMT2A-r ALL, revealing their potential as biomarkers for disease classification, risk stratification, and treatment response prediction. Understanding their interplay with KMT2A fusion proteins not only provides new insights into leukemogenesis but also highlights promising opportunities for therapeutic intervention and precision medicine in this high-risk leukemia subtype.

Comparative analysis with idelalisib revealed similar toxicity profiles to Qona11, distinct from vincristine. In vivo studies in NOD/SCID mice bearing Jurkat xenografts showed that Qona11 (100 mg.kg-1) was well tolerated with no systemic toxicity, although it did not inhibit leukemia cell proliferation in immune-independent models. Overall, Qona11 exhibits promising anticancer activity and low systemic toxicity, warranting further preclinical investigation in solid tumor models and combination therapies.

P1, N=71, Active, not recruiting, City of Hope Medical Center | Trial completion date: Sep 2025 --> Jul 2026 | Trial primary completion date: Sep 2025 --> Jul 2026

P=N/A, N=10000, Recruiting, Goethe University | Trial completion date: Dec 2030 --> Dec 2035 | Trial primary completion date: Dec 2025 --> Dec 2030

Blinatumomab and inotuzumab ozogamicin have become established treatments, enhancing remission rates, measurable residual disease clearance, and overall survival in relapsed/refractory disease, and these agents, are now increasingly incorporated into frontline therapy...In acute myeloid leukemia (AML), gemtuzumab ozogamicin has shown significant clinical benefits, particularly in molecularly defined subsets...This review highlights how immunotherapy has reshaped treatment paradigms across acute leukemias, underscoring successful experiences in B-ALL. These insights emphasize the need for continued innovation to overcome existing hurdles in AML and T-ALL, ultimately aiming to enhance patient outcomes and quality of life.

Collectively, these advances highlight the potential of cellular therapies in high-risk leukemias and underscore the importance of continued innovation to improve outcomes in these historically treatment-refractory populations. Using a real-world case, we highlight the major challenges and innovative strategies shaping CAR T-cell therapy for T-cell acute lymphoblastic leukemia and acute myeloid leukemia.

This case highlights the diagnostic challenges of HLH in immunocompromised children, where early signs such as fever and cytopenias may be misattributed to sepsis or chemotherapy-related complications. It underscores the importance of including HLH in the differential diagnosis of ALF in high-risk patients and demonstrates that prompt recognition and targeted treatment of the hyperinflammatory state can be lifesaving, even in severe presentations.

P1, N=24, Recruiting, Ohio State University Comprehensive Cancer Center | Not yet recruiting --> Recruiting

At the molecular level, luteolin significantly downregulated the protein expression of p-PI3K, p-AKT, p-STAT3 and BCL-2, while upregulating the protein expression of BAX, cleaved caspase-3, and cleaved caspase-9. Luteolin may exert anti-Ph + ALL effects through the PI3K/AKT signaling pathway, accompanied by the regulation of other targets such as STAT3, which provides a theoretical basis for the development and screening of novel anti-Ph + ALL therapies.