Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

CAR T-cell therapy in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis

Bone Marrow Transplantation (2026)Cite this article

Subjects

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (B-ALL), with high remission rates across various CAR T-cell constructs. However, the durability of these responses remains a major challenge, with many patients experiencing relapse after an initial remission. This systematic review and meta-analysis aimed to compare the efficacy and safety of different CAR T-cell constructs across 40 clinical trials, including a total of 1540 R/R B-ALL patients. We assessed the impact of patient demographics, prior treatment exposure, and construct characteristics on treatment outcomes. The pooled complete remission rate (CRR) was 83.4% (I2 = 49%), with a minimal residual disease-negative complete remission (MRDneg-CR/CRi) rate of 92.7% (I2 = 48%). 4-1BB co-stimulatory domain constructs showed higher MRDneg-CR/CRi rates compared with CD28 (94.0% vs. 84.4%p = 0.048) and a lower incidence of immune effector cell-associated neurotoxicity syndrome. Additionally, CAR T-cell products targeting CD19 or CD19/CD22 patients presented higher MRDneg-CR/CRi rates than those targeting CD22 alone. In conclusion, our findings suggest that 4-1BB-based CAR T-cell therapy targeting CD19 offers the best efficacy and safety profile in R/R B-ALL.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2: Forest plot with the pooled complete remission (CR) or CR with incomplete hematological recovery (CRi) and Minimal residual disease (MRDneg-CR/CRi) rate by co-stimulatory domain.
Fig. 3: Kaplan-Meier curves of Overall Survival.
Fig. 4

Similar content being viewed by others

Data availability

The data supporting the findings of this study are derived from publicly available published articles, which are cited in the manuscript. No individual participant data were generated or analyzed during the current study. All data extracted and analyzed are included in the published articles and supplementary materials referenced herein.

References

  1. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439–48. https://doi.org/10.1056/NEJMoa1709866.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Shah BD, Ghobadi A, Oluwole OO, Logan AC, Boissel N, Cassaday RD, et al. KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study. Lancet. 2021;398:491–502. https://doi.org/10.1016/S0140-6736(21)01222-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Roddie C, Dias J, O’Reilly MA, Abbasian M, Cadinanos-Garai A, Vispute K, et al. Durable responses and low toxicity after fast off-rate CD19 chimeric antigen receptor-t therapy in adults with relapsed or refractory B-cell acute lymphoblastic leukemia. J Clin Oncol. 2021;39:3352–63. https://doi.org/10.1200/JCO.21.00917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Leahy AB, Devine KJ, Li Y, Liu H, Myers R, DiNofia A, et al. Impact of high-risk cytogenetics on outcomes for children and young adults receiving CD19-directed CAR T-cell therapy. Blood. 2022;139:2173–85. https://doi.org/10.1182/blood.2021012727.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lamble AJ, Myers RM, Taraseviciute A, John S, Yates B, Steinberg SM, et al. Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells. Blood Adv. 2023;7:575–85. https://doi.org/10.1182/bloodadvances.2022007423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Molinos-Quintana Á, Alonso-Saladrigues A, Herrero B, Caballero-Velázquez T, Galán-Gómez V, Panesso M, et al. Impact of disease burden and late loss of B cell aplasia on the risk of relapse after CD19 chimeric antigen receptor T Cell (Tisagenlecleucel) infusion in pediatric and young adult patients with relapse/refractory acute lymphoblastic leukemia: role of B-cell monitoring. Front Immunol. 2024;14:1280580. https://doi.org/10.3389/fimmu.2023.1280580.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Myers RM, Li Y, Barz Leahy A, Barrett DM, Teachey DT, Callahan C, et al. Humanized CD19-targeted chimeric antigen receptor (CAR) T cells in CAR-naive and CAR-exposed children and young adults with relapsed or refractory acute lymphoblastic leukemia. J Clin Oncol. 2021;39:3044–55. https://doi.org/10.1200/JCO.20.03458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Park JH, Rivière I, Gonen M, Wang X, Sénéchal B, Curran KJ, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378:449–59. https://doi.org/10.1056/NEJMoa1709919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ortiz-Maldonado V, Rives S, Español-Rego M, Alonso-Saladrigues A, Montoro M, Magnano L, et al. Factors associated with the clinical outcome of patients with relapsed/refractory CD19 + acute lymphoblastic leukemia treated with ARI-0001 CART19-cell therapy. J Immunother Cancer. 2021;9:e003644 https://doi.org/10.1136/jitc-2021-003644.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Myers RM, Taraseviciute A, Steinberg SM, Lamble AJ, Sheppard J, Yates B, et al. Blinatumomab nonresponse and high-disease burden are associated with inferior outcomes after CD19-CAR for B-ALL. J Clin Oncol. 2022;40:932–44. https://doi.org/10.1200/JCO.21.01405.

    Article  CAS  PubMed  Google Scholar 

  11. Singh N, Frey NV, Engels B, Barrett DM, Shestova O, Ravikumar P, et al. Antigen-independent activation enhances the efficacy of 4-1BB-costimulated CD22 CAR T cells. Nat Med. 2021;27:842–50. https://doi.org/10.1038/s41591-021-01326-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Schultz LM, Jeyakumar N, Kramer AM, Sahaf B, Srinagesh H, Shiraz P, et al. CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results. Leukemia. 2024;38:963–8. https://doi.org/10.1038/s41375-024-02220-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. https://doi.org/10.1136/bmj.n71.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Schiavo JH. PROSPERO: an international register of systematic review protocols. Med Ref Serv Q. 2019;38:171–80. https://doi.org/10.1080/02763869.2019.1588072.

    Article  PubMed  Google Scholar 

  15. Liu N, Zhou Y, Lee JJ. IPDfromKM: reconstruct individual patient data from published Kaplan-Meier survival curves. BMC Med Res Methodol. 2021;21:111. https://doi.org/10.1186/s12874-021-01308-8.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Higgins JPT. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60. https://doi.org/10.1136/bmj.327.7414.557.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Berkey CS, Hoaglin DC, Mosteller F, Colditz GA. A random-effects regression model for meta-analysis. Stat Med. 1995;14:395–411. https://doi.org/10.1002/sim.4780140406.

    Article  CAS  PubMed  Google Scholar 

  18. Viechtbauer W. Conducting Meta-Analyses in R with the metafor Package. J Stat Softw 2010;36. https://doi.org/10.18637/jss.v036.i03.

  19. Van Houwelingen HC, Arends LR, Stijnen T. Advanced methods in meta-analysis: multivariate approach and meta-regression. Stat Med. 2002;21:589–624. https://doi.org/10.1002/sim.1040.

    Article  PubMed  Google Scholar 

  20. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. https://doi.org/10.1136/bmj.i4919.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Elsallab M, Ellithi M, Hempel S, Abdel-Azim H, Abou-el-Enein M. Long-term response to autologous anti-CD19 chimeric antigen receptor T cells in relapsed or refractory B cell acute lymphoblastic leukemia: a systematic review and meta-analysis. Cancer Gene Ther. 2023;30:845–54. https://doi.org/10.1038/s41417-023-00593-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Roddie C, Sandhu KS, Tholouli E, Logan AC, Shaughnessy P, Barba P, et al. Obecabtagene autoleucel in adults with B-cell acute lymphoblastic leukemia. N Engl J Med. 2024;391:2219–30. https://doi.org/10.1056/NEJMoa2406526.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schultz LM, Baggott C, Prabhu S, Pacenta HL, Phillips CL, Rossoff J, et al. Disease burden affects outcomes in pediatric and young adult B-cell lymphoblastic leukemia after commercial tisagenlecleucel: a pediatric real-world chimeric antigen receptor consortium report. J Clin Oncol. 2022;40:945–55. https://doi.org/10.1200/JCO.20.03585.

    Article  CAS  PubMed  Google Scholar 

  24. Rabian F, Beauvais D, Marchand T, Furst S, Huynh A, Brissot E, et al. Efficacy and tolerance of brexucabtagene autoleucel in adults with R/R B-ALL: A GRAALL study from the DESCAR-T registry. Blood Adv. 2024;8:5493–6. https://doi.org/10.1182/bloodadvances.2024013962.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Anagnostou T, Riaz IB, Hashmi SK, Murad MH, Kenderian SS. Anti-CD19 chimeric antigen receptor T-cell therapy in acute lymphocytic leukaemia: a systematic review and meta-analysis. Lancet Haematol. 2020;7:e816–26. https://doi.org/10.1016/S2352-3026(20)30277-5.

    Article  PubMed  Google Scholar 

  26. Weinkove R, George P, Dasyam N, McLellan AD. Selecting costimulatory domains for chimeric antigen receptors: functional and clinical considerations. Clin Transl Immunol. 2019;8:e1049. https://doi.org/10.1002/cti2.1049.

    Article  Google Scholar 

  27. Guedan S, Madar A, Casado-Medrano V, Shaw C, Wing A, Liu F, et al. Single residue in CD28-costimulated CAR-T cells limits long-term persistence and antitumor durability. J Clin Invest. 2020;130:3087–97. https://doi.org/10.1172/JCI133215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bachy E, Le Gouill S, Di Blasi R, Sesques P, Manson G, Cartron G, et al. A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma. Nat Med. 2022;28:2145–54. https://doi.org/10.1038/s41591-022-01969-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schubert M-L, Schmitt A, Hückelhoven-Krauss A, Neuber B, Kunz A, Waldhoff P, et al. Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial. J Hematol OncolJ Hematol Oncol. 2023;16:79. https://doi.org/10.1186/s13045-023-01470-0.

    Article  CAS  Google Scholar 

  30. Shah BD, Cassaday RD, Park JH, Houot R, Oluwole OO, Logan AC, et al. Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3. J Immunother Cancer. 2023;11:e007118. https://doi.org/10.1136/jitc-2023-007118.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Gauthier J, Hirayama AV, Purushe J, Hay KA, Lymp J, Li DH, et al. Feasibility and efficacy of CD19-targeted CAR T cells with concurrent ibrutinib for CLL after ibrutinib failure. Blood. 2020;135:1650–60. https://doi.org/10.1182/blood.2019002936.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Myers RM, Devine K, Li Y, Lawrence S, Leahy AB, Liu H, et al. Reinfusion of CD19 CAR T cells for relapse prevention and treatment in children with acute lymphoblastic leukemia. Blood Adv. 2024;8:2182–92. https://doi.org/10.1182/bloodadvances.2024012885.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. An L, Lin Y, Deng B, Yin Z, Zhao D, Ling Z, et al. Humanized CD19 CAR-T cells in relapsed/refractory B-ALL patients who relapsed after or failed murine CD19 CAR-T therapy. BMC Cancer. 2022;22:393. https://doi.org/10.1186/s12885-022-09489-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lynn RC, Weber EW, Sotillo E, Gennert D, Xu P, Good Z, et al. c-Jun overexpression in CAR T cells induces exhaustion resistance. Nature. 2019;576:293–300. https://doi.org/10.1038/s41586-019-1805-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Cao J, Wang G, Cheng H, Wei C, Qi K, Sang W, et al. Potent anti-leukemia activities of humanized CD19-targeted Chimeric antigen receptor T (CAR-T) cells in patients with relapsed/refractory acute lymphoblastic leukemia. Am J Hematol. 2018;93:851–8. https://doi.org/10.1002/ajh.25108.

    Article  CAS  PubMed  Google Scholar 

  36. Boulch M, Cazaux M, Loe-Mie Y, Thibaut R, Corre B, Lemaître F, et al. A cross-talk between CAR T cell subsets and the tumor microenvironment is essential for sustained cytotoxic activity. Sci Immunol. 2021;6:eabd4344. https://doi.org/10.1126/sciimmunol.abd4344.

    Article  CAS  PubMed  Google Scholar 

  37. Jiang H, Li C, Yin P, Guo T, Liu L, Xia L, et al. Anti-CD19 chimeric antigen receptor-modified T-cell therapy bridging to allogeneic hematopoietic stem cell transplantation for relapsed/refractory B-cell acute lymphoblastic leukemia: An open-label pragmatic clinical trial. Am J Hematol. 2019;94:1113–22. https://doi.org/10.1002/ajh.25582.

    Article  CAS  PubMed  Google Scholar 

  38. Gabelli M, Oporto-Espuelas M, Burridge S, Chu J, Farish S, Hedges E, et al. Maintenance therapy for early loss of B-cell aplasia after anti-CD19 CAR T-cell therapy. Blood Adv. 2024;8:1959–63. https://doi.org/10.1182/bloodadvances.2023011168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Maintenance therapy for early loss of B-cell aplasia after anti-CD19 CAR T-cell therapy | Blood Advances | American Society of Hematology n.d. https://ashpublications.org/bloodadvances/article/8/8/1959/498307/Maintenance-therapy-for-early-loss-of-B-cell (accessed November 12, 2025).

  40. Laetsch TW, Maude SL, Rives S, Hiramatsu H, Bittencourt H, Bader P, et al. Three-Year Update of Tisagenlecleucel in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia in the ELIANA Trial. J Clin Oncol. 2023;41:1664–9. https://doi.org/10.1200/JCO.22.00642.

    Article  CAS  PubMed  Google Scholar 

  41. Kwag D, Yoon J-H, Min GJ, Park S-S, Park S, Lee S-E, et al. Outcome of second allogeneic hematopoietic cell transplantation in adult patients with relapsed B-cell acute lymphoblastic leukemia in the era of new immunotherapeutic agents. Bone Marrow Transpl. 2025;60:1249–57. https://doi.org/10.1038/s41409-025-02639-6.

    Article  CAS  Google Scholar 

  42. Maude SL, Teachey DT, Porter DL, Grupp SA. CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood. 2015;125:4017–23. https://doi.org/10.1182/blood-2014-12-580068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hu Y, Wu Z, Luo Y, Shi J, Yu J, Pu C, et al. Potent Anti-leukemia Activities of Chimeric Antigen Receptor–Modified T Cells against CD19 in Chinese Patients with Relapsed/Refractory Acute Lymphocytic Leukemia. Clin Cancer Res. 2017;23:3297–306. https://doi.org/10.1158/1078-0432.CCR-16-1799.

    Article  CAS  PubMed  Google Scholar 

  44. Jacoby E, Bielorai B, Avigdor A, Itzhaki O, Hutt D, Nussboim V, et al. Locally produced CD19 CAR T cells leading to clinical remissions in medullary and extramedullary relapsed acute lymphoblastic leukemia. Am J Hematol. 2018;93:1485–92. https://doi.org/10.1002/ajh.25274.

    Article  CAS  PubMed  Google Scholar 

  45. Li S, Zhang J, Wang M, Fu G, Li Y, Pei L, et al. Treatment of acute lymphoblastic leukaemia with the second generation of CD 19 CAR -T containing either CD 28 or 4-1 BB. Br J Haematol. 2018;181:360–71. https://doi.org/10.1111/bjh.15195.

    Article  CAS  PubMed  Google Scholar 

  46. Frey NV, Shaw PA, Hexner EO, Pequignot E, Gill S, Luger SM, et al. Optimizing chimeric antigen receptor T-cell therapy for adults with acute lymphoblastic leukemia. J Clin Oncol. 2020;38:415–22. https://doi.org/10.1200/JCO.19.01892.

    Article  CAS  PubMed  Google Scholar 

  47. Curran KJ, Margossian SP, Kernan NA, Silverman LB, Williams DA, Shukla N, et al. Toxicity and response after CD19-specific CAR T-cell therapy in pediatric/young adult relapsed/refractory B-ALL. Blood. 2019;134:2361–8. https://doi.org/10.1182/blood.2019001641.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Hay KA, Gauthier J, Hirayama AV, Voutsinas JM, Wu Q, Li D, et al. Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR T-cell therapy. Blood. 2019;133:1652–63. https://doi.org/10.1182/blood-2018-11-883710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ghorashian S, Kramer AM, Onuoha S, Wright G, Bartram J, Richardson R, et al. Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nat Med. 2019;25:1408–14. https://doi.org/10.1038/s41591-019-0549-5.

    Article  CAS  PubMed  Google Scholar 

  50. Pan J, Niu Q, Deng B, Liu S, Wu T, Gao Z, et al. CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia. Leukemia. 2019;33:2854–66. https://doi.org/10.1038/s41375-019-0488-7.

    Article  CAS  PubMed  Google Scholar 

  51. Jiang H, Liu L, Guo T, Wu Y, Ai L, Deng J, et al. Improving the safety of CAR-T cell therapy by controlling CRS-related coagulopathy. Ann Hematol. 2019;98:1721–32. https://doi.org/10.1007/s00277-019-03685-z.

    Article  CAS  PubMed  Google Scholar 

  52. Tu S, Huang R, Guo Z, Deng L, Song C, Zhou X, et al. Shortening the ex vivo culture of CD19-specific CAR T-cells retains potent efficacy against acute lymphoblastic leukemia without CAR T-cell-related encephalopathy syndrome or severe cytokine release syndrome. Am J Hematol. 2019;94:E322–5. https://doi.org/10.1002/ajh.25630.

    Article  PubMed  Google Scholar 

  53. Ma F, Ho J, Du H, Xuan F, Wu X, Wang Q, et al. Evidence of long-lasting anti-CD19 activity of engrafted CD19 chimeric antigen receptor–modified T cells in a phase I study targeting pediatrics with acute lymphoblastic leukemia. Hematol Oncol. 2019;37:601–8. https://doi.org/10.1002/hon.2672.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Shah NN, Highfill SL, Shalabi H, Yates B, Jin J, Wolters PL, et al. CD4/CD8 T-Cell Selection Affects Chimeric Antigen Receptor (CAR) T-Cell Potency and Toxicity: Updated Results From a Phase I Anti-CD22 CAR T-Cell Trial. J Clin Oncol. 2020;38:1938–50. https://doi.org/10.1200/JCO.19.03279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Dai H, Wu Z, Jia H, Tong C, Guo Y, Ti D, et al. Bispecific CAR-T cells targeting both CD19 and CD22 for therapy of adults with relapsed or refractory B cell acute lymphoblastic leukemia. J Hematol OncolJ Hematol Oncol. 2020;13:30. https://doi.org/10.1186/s13045-020-00856-8.

    Article  CAS  Google Scholar 

  56. Zhang X, Lu X, Yang J, Zhang G, Li J, Song L, et al. Efficacy and safety of anti-CD19 CAR T-cell therapy in 110 patients with B-cell acute lymphoblastic leukemia with high-risk features. Blood Adv. 2020;4:2325–38. https://doi.org/10.1182/bloodadvances.2020001466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wang J, Mou N, Yang Z, Li Q, Jiang Y, Meng J, et al. Efficacy and safety of humanized anti-CD19-CAR-T therapy following intensive lymphodepleting chemotherapy for refractory/relapsed B acute lymphoblastic leukaemia. Br J Haematol. 2020;191:212–22. https://doi.org/10.1111/bjh.16623.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. An F, Wang H, Liu Z, Wu F, Zhang J, Tao Q, et al. Influence of patient characteristics on chimeric antigen receptor T cell therapy in B-cell acute lymphoblastic leukemia. Nat Commun. 2020;11:5928. https://doi.org/10.1038/s41467-020-19774-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Gu R, Liu F, Zou D, Xu Y, Lu Y, Liu B, et al. Efficacy and safety of CD19 CAR T constructed with a new anti-CD19 chimeric antigen receptor in relapsed or refractory acute lymphoblastic leukemia. J Hematol OncolJ Hematol Oncol. 2020;13:122. https://doi.org/10.1186/s13045-020-00953-8.

    Article  CAS  Google Scholar 

  60. Heng G, Jia J, Li S, Fu G, Wang M, Qin D, et al. Sustained therapeutic efficacy of humanized anti-CD19 chimeric antigen receptor T cells in relapsed/refractory acute lymphoblastic leukemia. Clin Cancer Res. 2020;26:1606–15. https://doi.org/10.1158/1078-0432.CCR-19-1339.

    Article  CAS  PubMed  Google Scholar 

  61. Shah NN, Lee DW, Yates B, Yuan CM, Shalabi H, Martin S, et al. Long-term follow-up of CD19-CAR T-cell therapy in children and young adults with B-ALL. J Clin Oncol. 2021;39:1650–9. https://doi.org/10.1200/JCO.20.02262.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Shah BD, Bishop MR, Oluwole OO, Logan AC, Baer MR, Donnellan WB, et al. KTE-X19 anti-CD19 CAR T-cell therapy in adult relapsed/refractory acute lymphoblastic leukemia: ZUMA-3 phase 1 results. Blood. 2021;138:11–22. https://doi.org/10.1182/blood.2020009098.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Cordoba S, Onuoha S, Thomas S, Pignataro DS, Hough R, Ghorashian S, et al. CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. Nat Med. 2021;27:1797–805. https://doi.org/10.1038/s41591-021-01497-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Tan Y, Cai H, Li C, Deng B, Song W, Ling Z, et al. A novel full-human CD22-CAR T cell therapy with potent activity against CD22low B-ALL. Blood Cancer J. 2021;11:71. https://doi.org/10.1038/s41408-021-00465-9.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Ortíz-Maldonado V, Rives S, Castellà M, Alonso-Saladrigues A, Benítez-Ribas D, Caballero-Baños M, et al. CART19-BE-01: a multicenter trial of ARI-0001 cell therapy in patients with CD19+ relapsed/refractory malignancies. Mol Ther. 2021;29:636–44. https://doi.org/10.1016/j.ymthe.2020.09.027.

    Article  CAS  PubMed  Google Scholar 

  66. Kadauke S, Myers RM, Li Y, Aplenc R, Baniewicz D, Barrett DM, et al. Risk-adapted preemptive tocilizumab to prevent severe cytokine release syndrome after CTL019 for pediatric B-cell acute lymphoblastic leukemia: a prospective clinical trial. J Clin Oncol. 2021;39:920–30. https://doi.org/10.1200/JCO.20.02477.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gong W-J, Qiu Y, Li M-H, Chen L-Y, Li Y-Y, Yu J-Q, et al. Investigation of the risk factors to predict cytokine release syndrome in relapsed or refractory B-cell acute lymphoblastic leukemia patients receiving IL-6 knocking down anti-CD19 chimeric antigen receptor T-cell therapy. Front Immunol. 2022;13:922212. https://doi.org/10.3389/fimmu.2022.922212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Talleur AC, Qudeimat A, Métais J-Y, Langfitt D, Mamcarz E, Crawford JC, et al. Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL. Blood Adv. 2022;6:5737–49. https://doi.org/10.1182/bloodadvances.2021006293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Shalabi H, Qin H, Su A, Yates B, Wolters PL, Steinberg SM, et al. CD19/22 CAR T cells in children and young adults with B-ALL: phase 1 results and development of a novel bicistronic CAR. Blood. 2022;140:451–63. https://doi.org/10.1182/blood.2022015795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ceppi F, Wilson AL, Annesley C, Kimmerly GR, Summers C, Brand A, et al. Modified manufacturing process modulates CD19CAR T-cell engraftment fitness and leukemia-free survival in pediatric and young adult subjects. Cancer Immunol Res. 2022;10:856–70. https://doi.org/10.1158/2326-6066.CIR-21-0501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Li M, Xue S-L, Tang X, Xu J, Chen S, Han Y, et al. The differential effects of tumor burdens on predicting the net benefits of ssCART-19 cell treatment on r/r B-ALL patients. Sci Rep. 2022;12:378. https://doi.org/10.1038/s41598-021-04296-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Wang J, Zhang X, Zhou Z, Liu Y, Yu L, Jia L, et al. A novel adoptive synthetic TCR and antigen receptor (STAR) T-Cell therapy for B-Cell acute lymphoblastic leukemia. Am J Hematol. 2022;97:992–1004. https://doi.org/10.1002/ajh.26586.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Statistics unit, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

    Victor Navarro & Guillermo Villacampa

  2. Department of Hematology, University Hospital Vall d’Hebron, Barcelona, Spain

    Gloria Iacoboni, Sergi Camarillas, Cecilia Carpio, Mario Sánchez-Salinas, Samantha Feijoo, Francesc Bosch & Pere Barba

  3. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain

    Gloria Iacoboni, Cecilia Carpio, Mario Sánchez-Salinas, Francesc Bosch & Pere Barba

  4. SOLTI Cancer Research Group, Barcelona, Spain

    Guillermo Villacampa

  5. Cell Engineering and Hematologic Immunotherapy lab. Vall Hebron Institute of Oncology, Barcelona, Spain

    Pere Barba

Authors
  1. Victor Navarro
    View author publications

    Search author on:PubMed Google Scholar

  2. Gloria Iacoboni
    View author publications

    Search author on:PubMed Google Scholar

  3. Sergi Camarillas
    View author publications

    Search author on:PubMed Google Scholar

  4. Cecilia Carpio
    View author publications

    Search author on:PubMed Google Scholar

  5. Mario Sánchez-Salinas
    View author publications

    Search author on:PubMed Google Scholar

  6. Samantha Feijoo
    View author publications

    Search author on:PubMed Google Scholar

  7. Francesc Bosch
    View author publications

    Search author on:PubMed Google Scholar

  8. Guillermo Villacampa
    View author publications

    Search author on:PubMed Google Scholar

  9. Pere Barba
    View author publications

    Search author on:PubMed Google Scholar

Contributions

VN, GI, SC, GV, and PB contributed to the conception and original idea of the study. VN, GI, SC, and PB were responsible for data collection. VN and GV performed the data analysis and developed the analytical software. VN, GI, GV, and PB drafted the initial version of the manuscript. CC, MS, SF, and FB critically reviewed and edited the manuscript. All authors reviewed the final version of the manuscript and approved it for submission.

Corresponding author

Correspondence to Pere Barba.

Ethics declarations

Competing interests

VN declares no conflicts of interest. GI reports consultancy and honoraria from Novartis, Roche, Kite/Gilead, Bristol-Myers Squibb, AbbVie, Janssen, Sandoz, Miltenyi, and AstraZeneca. SC declares no conflicts of interest. CC has received consultancy or advisory fees from Regeneron, BMS, and Takeda; and honoraria from Takeda and Novartis. MS-S has received honoraria for presentations from Kite and support for attending meetings from Takeda. SF declares no conflicts of interest. FB has received honoraria from Roche, Novartis, AstraZeneca, Lilly, BMS GmbH & Co KG, Merck, Johnson & Johnson/Janssen, BeiGene, Advantage Pharmaceuticals, ASCEND Therapeutics, and AbbVie; has served on advisory boards or as a consultant for AstraZeneca, Roche/Genentech, Janssen-Cilag, Lilly, AbbVie, Kite (a Gilead company), BeiGene, and Novartis; has participated in speakers’ bureaus for AbbVie, Janssen, Roche, AstraZeneca, Merck, Bristol Myers Squibb/Celgene, Kite/Gilead, and Johnson & Johnson/Janssen; has received research funding from Janssen and AstraZeneca; and has received travel support from AstraZeneca, BeiGene, Johnson & Johnson/Janssen, and AbbVie. GV has received speaker fees from Pfizer, MSD, GSK, and Pierre Fabre; consultancy fees from Reveal Genomics; and has served in an advisory role with AstraZeneca, all outside the submitted work. PB has received honoraria from Allogene, Amgen, BMS, Kite/Gilead, Janssen, Jazz Pharmaceuticals, Miltenyi, Novartis, and Nektar.

Ethics approval and consent to participate

This study is a systematic review and meta-analysis based exclusively on data from previously published studies. No new data were collected, and no individual patient-level data were accessed or analyzed. Therefore, ethical approval and informed consent were not required for this study.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Navarro, V., Iacoboni, G., Camarillas, S. et al. CAR T-cell therapy in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis. Bone Marrow Transplant (2026). https://doi.org/10.1038/s41409-026-02803-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41409-026-02803-6

Search

Advanced search

Quick links