Overview
B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic malignancy characterized by the proliferation of immature B-cell precursors. Tisagenlecleucel, a chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19, has emerged as a significant treatment option for relapsed/refractory cases in pediatric and adolescent populations 12.Diagnosis
Bone marrow aspiration and biopsy to identify blast cells expressing CD19 2.
Flow cytometry for immunophenotyping to confirm B-cell lineage 2.
Cytogenetic and molecular genetic testing to assess specific genetic abnormalities 2.Management
First-line treatments: Standard chemotherapy regimens such as vincristine, prednisone, daunorubicin, and asparaginase (VADL or similar protocols) 2.
CAR-T therapy: Tisagenlecleucel for relapsed/refractory cases 12.
Supportive care: Management of cytokine release syndrome (CRS) and neurological toxicities with corticosteroids and tocilizumab 12.
Monitoring: Close surveillance for cardiovascular toxicities including mitral valve disease, hypotension, and capillary leak syndrome 1.Special Populations
Pediatrics: Tisagenlecleucel shows efficacy but requires vigilant monitoring for cardiovascular adverse events, particularly in the early days post-treatment 1.
Comorbidities: Concomitant neurological medications may increase risk of cardiovascular toxicity 1.Key Recommendations
Implement close monitoring for cardiovascular adverse events within the first week post-CAR-T infusion, especially in pediatric patients (Evidence: Moderate 1).
Consider the potential increased risk of fatal cardiovascular events in patients on concomitant neurological medications (Evidence: Weak 1).
Adhere to comprehensive best practice guidelines for patient selection, treatment administration, and long-term follow-up developed by EBMT, JACIE, and EHA to ensure high-quality care (Evidence: Expert opinion 2).References
1 Wang G, Su L, Liu Y, Yang X, Li Y, Mei Q et al.. Cardiovascular toxicity of tisagenlecleucel in children and adolescents: analysis of spontaneous reports submitted to FAERS. Frontiers in immunology 2025. link
2 Hayden PJ, Roddie C, Bader P, Basak GW, Bonig H, Bonini C et al.. Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA). Annals of oncology : official journal of the European Society for Medical Oncology 2022. link
3 . CD19 CAR T-cell Clinical Outcome Is Associated with the Gut Microbiome. Cancer discovery 2022. link