CAR-T cell therapies
DOI:
https://doi.org/10.46765/2675-374X.2025v6n1e303Keywords:
Chimeric Antigen Receptors, T-Cell Therapy, Gene Therapy, Hematologic NeoplasmAbstract
Chimeric antigen receptor T-cell (CAR-T) therapy has rapidly reshaped the therapeutic landscape for children and adolescents with relapsed or refractory hematologic malignancies. In Brazil, the integration of CAR-T therapy into pediatric oncology practice faces unique logistical, regulatory, and socioeconomic challenges, highlighting the need for structured, context-specific guidance. This national pediatric consensus summarizes current evidence and provides practical recommendations for indications, leukapheresis, washout strategies, bridging therapy, lymphodepletion, infusion procedures, and the management of toxicities, including cytokine release syndrome, immune effector cellassociated neurotoxicity syndrome, coagulopathy, and HLH-like syndromes. Long-term follow-up, immune reconstitution monitoring, vaccination guidance, and survivorship considerations are also addressed. Emerging applications in myeloid malignancies, T-cell neoplasms, and solid tumors—particularly GD2-targeted CAR-T cells for neuroblastoma—are briefly reviewed. By consolidating multidisciplinary expertise from institutions across Brazil, this document sought to support safe, effective, and equitable implementation of CAR-T therapy in the pediatric population and encourages continued development of local manufacturing and academic protocols to expand access to this transformative treatment.
References
1. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in children and young adults with B-Cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439–48. https://doi.org/10.1056/NEJMoa1709866 DOI: https://doi.org/10.1056/NEJMoa1709866
2. Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368(16):1509–18. https://doi.org/10.1056/NEJMoa121513 DOI: https://doi.org/10.1056/NEJMoa1215134
3. Silva Junior JB, Takao MRM, Parca RM. Advanced therapy medicinal products: an introduction to risk management. Vigil. sanit. debate. 2018.
4. Kanate AS, Majhail NS, Savani BN, Bredeson C, Champlin RE, Crawford S, Giralt SA, LeMaistre CF, Marks DI, Omel JL, Orchard PJ, Palmer J, Saber W, Veys PA, Carpenter PA, Hamadani M. Indications for hematopoietic cell transplantation and immune effector cell therapy: guidelines from the American Society for Transplantation and Cellular Therapy. Biol Blood Marrow Transplant. 2020;26(7):1247–56. https://doi.org/10.1016/j.bbmt.2020.03.002 DOI: https://doi.org/10.1016/j.bbmt.2020.03.002
5. McNerney KO, Schultz LM. Tisagenlecleucel in practice: real-world lessons in pediatric and young adult B-ALL. Transplant Cell Ther. 2025;31(6):351.e1–e11. https://doi.org/10.1016/j.jtct.2025.02.016 DOI: https://doi.org/10.1016/j.jtct.2025.02.016
6. Laetsch TW, Maude SL, Balduzzi A, Rives S, Bittencourt H, Boyer MW, Buechner J, De Moerloose B, Qayed M, Phillips CL, Pulsipher MA, Hiramatsu H, Tiwari R, Grupp SA. Tisagenlecleucel in pediatric and young adult patients with Down syndrome-associated relapsed/refractory acute lymphoblastic leukemia. Leukemia. 2022;36(6):1508–15. https://doi.org/10.1038/s41375-022-01550-z DOI: https://doi.org/10.1038/s41375-022-01550-z
7. Qayed M, McGuirk JP, Myers GD, Parameswaran V, Waller EK, Holman P, Rodrigues M, Clough LF, Willert J. Leukapheresis guidance and best practices for optimal chimeric antigen receptor T-cell manufacturing. Cytotherapy. 2022;24(9):869–78. https://doi.org/10.1016/j.jcyt.2022.05.003 DOI: https://doi.org/10.1016/j.jcyt.2022.05.003
8. Bonig H, Chabannon C, Lozano M. Providing the starting material to the manufacturer of an approved and commercially available autologous CAR-T cell treatment. In: Kröger N, Gribben J, Chabannon C, Yakoub- Agha I, Einsele H, editors. The EBMT/EHA CAR-T Cell Handbook. Cham: Springer; 2022. p. 31–6. https://doi.org/10.1007/978-3-030-94353-0_6 DOI: https://doi.org/10.1007/978-3-030-94353-0_6
9. Baruchel A. Bridging to CAR-T cells in children, adolescents, and young adults with ALL. In: Kröger N, Gribben J, Chabannon C, Yakoub-Agha I, Einsele H, editors. The EBMT/EHA CAR-T Cell Handbook. Cham: Springer; 2022. p. 115–8. https://doi.org/10.1007/978-3-030-94353-0_21 DOI: https://doi.org/10.1007/978-3-030-94353-0_21
10. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN, Steinberg SM, Stroncek D, Tschernia N, Yuan C, Zhang H, Zhang L, Rosenberg SA, Wayne AS, Mackall CL. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385(9967):517-528. https://doi.org/10.1016/S0140-6736(14)61403-3 DOI: https://doi.org/10.1016/S0140-6736(14)61403-3
11. Yakoub-Agha I, Chabannon C, Bader P, Basak GW, Bonig H, Ciceri F, Corbacioglu S, Duarte RF, Einsele H, Hudecek M, Kersten MJ, Köhl U, Kuball J, Mielke S, Mohty M, Murray J, Nagler A, Robinson S, Saccardi R, Sanchez-Guijo F, Snowden JA, Srour M, Styczynski J, Urbano-Ispizua A, Hayden PJ, Kröger N. Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Haematologica. 2020;105(2):297–316. https://doi.org/10.3324/haematol.2019.229781 DOI: https://doi.org/10.3324/haematol.2019.229781
12. Mahadeo KM, Khazal SJ, Abdel-Azim H, Fitzgerald JC, Taraseviciute A, Bollard CM, Tewari P, Duncan C, Traube C, McCall D, Steiner ME, Cheifetz IM, Lehmann LE, Mejia R, Slopis JM, Bajwa R, Kebriaei P, Martin PL, Moffet J, McArthur J, Petropoulos D, O’Hanlon Curry J, Featherston S, Foglesong J, Shoberu B, Gulbis A, Mireles ME, Hafemeister L, Nguyen C, Kapoor N, Rezvani K, Neelapu SS, Shpall EJ; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy. Nat Rev Clin Oncol. 2019;16(1):45–63. https://doi.org/10.1038/s41571-018-0075-2 DOI: https://doi.org/10.1038/s41571-018-0075-2
13. CARTOX 2025. Available at: https://play.google.com/store/apps/detailsid=org.mdanderson.cartox&hl=pt&pli=1
14. CARTLOG 2025. Available at: https://play.google.com/store/apps/detailsid=br.einstein.cartlog&hl=pt&pli=1
15. Johnsrud A, Craig J, Baird J, Spiegel J, Muffly L, Zehnder J, Tamaresis J, Negrin R, Johnston L, Arai S, Shizuru J, Lowsky R, Meyer E, Weng WK, Shiraz P, Rezvani A, Latchford T, Mackall C, Miklos D, Frank M, Sidana S. Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy. Blood Adv. 2021;5(21):4465–75. https://doi.org/10.1182/bloodadvances.2021004716 DOI: https://doi.org/10.1182/bloodadvances.2021004716
16. Jiang H, Liu L, Guo T, Wu Y, Ai L, Deng J, Dong J, Mei H, Hu Y. Improving the safety of CAR-T cell therapy by controlling CRS-related coagulopathy. Ann Hematol. 2019;98(7):1721–32. https://doi.org/10.1007/s00277-019-03685-z DOI: https://doi.org/10.1007/s00277-019-03685-z
17. Fried S, Avigdor A, Bielorai B, Meir A, Besser MJ, Schachter J, Shimoni A, Nagler A, Toren A, Jacoby E. Early and late hematologic toxicity following CD19 CAR-T cells. Bone Marrow Transplant. 2019; 54(10): 1643–50. https://doi.org/10.1038/s41409-019-0487-3 DOI: https://doi.org/10.1038/s41409-019-0487-3
18. Epperly R, Giordani VM, Mikkilineni L, Shah NN. Early and late toxicities of chimeric antigen receptor T-cells. Hematol Oncol Clin North Am. 2023;37(6):1169–88. https://doi.org/10.1016/j.hoc.2023.05.010 DOI: https://doi.org/10.1016/j.hoc.2023.05.010
19. Hayden P, Gagelmann N, Snowden J. Long-term follow-up and late effects. In: Kröger N, Gribben J, Chabannon C, Yakoub-Agha I, Einsele H, editors. The EBMT/EHA CAR-T Cell Handbook. Cham: Springer; 2022. p. 36. https://doi.org/10.1007/978-3-030-94353-0_36 DOI: https://doi.org/10.1007/978-3-030-94353-0_36
20. Corradini P, Trümper L. Developments in other haematological malignancies: other lymphoid malignancies. In: Kröger N, Gribben J, Chabannon C, Yakoub-Agha I, Einsele H, editors. The EBMT/EHA CAR-T Cell Handbook. Cham: Springer; 2022. p. 91–5. https://doi.org/10.1007/978-3-030-94353-0_17 DOI: https://doi.org/10.1007/978-3-030-94353-0_17
21. Ferrand C, Rambaldi F. Myeloid malignancies. In: Kröger N, Gribben J, Chabannon C, Yakoub-Agha I, Einsele H, editors. The EBMT/EHA CAR-T Cell Handbook. Cham: Springer; 2022. p. 97–103. https://doi.org/10.1007/978-3-030-94353-0_18 DOI: https://doi.org/10.1007/978-3-030-94353-0_18
22. Pedrazzoli P, Haanen JBAG. Developments in solid tumours. In: Kröger N, Gribben J, Chabannon C, Yakoub-Agha I, Einsele H, editors. The EBMT/EHA CAR-T Cell Handbook. Cham: Springer; 2022. p. 105–8. https://doi.org/10.1007/978-3-030-94353-0_19 DOI: https://doi.org/10.1007/978-3-030-94353-0_19
23. Anderson J, Barone G, Zehner A. GD2 targeting CAR T cells for neuroblastoma. EJC Paediatr Oncol. 2024; 4:100179. https://doi.org/10.1016/j.ejcped.2024.100179 DOI: https://doi.org/10.1016/j.ejcped.2024.100179
24. Del Bufalo F, De Angelis B, Caruana I, Del Baldo G, De Ioris MA, Serra A, et al. GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma. N Engl J Med. 2023;388:1284–95. https://doi.org/10.1056/NEJMoa2210859. DOI: https://doi.org/10.1056/NEJMoa2210859
25. Heczey A, Xu X, Courtney AN, Tian G, Barragan GA, Guo L, et al. Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: updated phase 1 trial interim results. Nat Med. 2023;29(6):1379–88. https://doi.org/10.1038/s41591-023-02363-y DOI: https://doi.org/10.1038/s41591-023-02363-y
26. Straathof K, Pulè M, Yvon E, Thomas S, Nguyen K, Stauss H, et al. Antitumor activity without on-target off tumor toxicity of GD2-chimeric antigen receptor T cells in patients with neuroblastoma. Sci Transl Med. 2020;12(571):eabd6169. https://doi.org/10.1126/scitranslmed.abd6169. DOI: https://doi.org/10.1126/scitranslmed.abd6169
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Copyright (c) 2026 Antonella Zanette, Adriana Martins de Sousa, Cilmara Kuwahara , Mariane Farherr Caleffi, Natalia Maria Tavares Ferreira Borges, Adriana Seber, Julia Lopes Garcia
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