LATEST ADVANCES IN THE TREATMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA: A NARRATIVE REVIEW OF NOVEL TARGETED AND IMMUNOTHERAPEUTIC STRATEGIES
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.6617Keywords:
Acute Lymphoblastic Leukemia, Immunotherapy, Bispecific Antibodies, Chimeric Antigen Receptor T-cell Therapy, Targeted Therapy, Measurable Residual DiseaseAbstract
Objectives: Acute lymphoblastic leukemia (ALL) treatment is changing rapidly as immunotherapy, targeted drugs, and measurable residual disease (MRD) testing move into routine care. This review summarizes major therapeutic advances reported between 2019 and 2026.
Methods: This SANRA-informed narrative review synthesized peer-reviewed clinical studies, major guidelines and consensus recommendations, and regulatory sources, emphasizing evidence from January 2019 through 15 August 2026 with selective earlier landmark studies. Evidence was summarized descriptively; no formal systematic-review screening, risk-of-bias assessment, GRADE evaluation, or meta-analysis was performed.
Results: In ECOG-ACRIN E1910, adding blinatumomab to consolidation chemotherapy improved 3-year overall survival in adults with MRD-negative remission from 68% to 85% [33]. Preliminary conference-reported phase III GIMEMA ALL2820 results favored ponatinib plus blinatumomab over imatinib plus chemotherapy for complete hematologic remission, day-133 MRD response, and 18-month event-free survival in newly diagnosed Ph+ ALL [69]. CD19-directed CAR T-cell therapies produce high remission rates in R/R B-cell precursor ALL [35, 43, 46], while revumenib provides a targeted option for R/R KMT2A-translocated acute leukemia [22, 56]. MRD increasingly informs risk-adapted treatment decisions [66].
Conclusions: ALL treatment is becoming more personalized and increasingly guided by immunotherapy, molecular targets, and MRD, although resistance, immune toxicity, transplantation decisions, cost, and unequal access remain important barriers.
References
Alaggio, R., Amador, C., Anagnostopoulos, I., Attygalle, A. D., Araujo, I. B. O., Berti, E., Bhagat, G., Borges, A. M., Boyer, D., Calaminici, M., Chadburn, A., Chan, J. K. C., Cheuk, W., Chng, W.-J., Choi, J. K., Chuang, S.-S., Coupland, S. E., Czader, M., Dave, S. S., … Xiao, W. (2022). The 5th edition of the World Health Organization classification of haematolymphoid tumours: Lymphoid neoplasms. Leukemia, 36(7), 1720–1748. https://doi.org/10.1038/s41375-022-01620-2
Ansuinelli, M., Peragine, N., De Propris, M. S., Puzzolo, M. C., Di Trani, M., Elia, L., Skert, C., Cairoli, R., Sica, S., Rambaldi, A., Tucci, A., Cerrano, M., Vallisa, D., Cardinali, V., Mulè, A., Chiaretti, S., Guarini, A., & Foà, R. (2026). Immunomodulatory effect of dasatinib plus blinatumomab versus ponatinib plus blinatumomab in newly diagnosed Ph+ acute lymphoblastic leukemia. Leukemia, 40(3), 577–586. https://doi.org/10.1038/s41375-025-02855-5
Arber, D. A., Orazi, A., Hasserjian, R. P., Borowitz, M. J., Calvo, K. R., Kvasnicka, H.-M., Wang, S. A., Bagg, A., Barbui, T., Branford, S., Bueso-Ramos, C. E., Cortes, J. E., Dal Cin, P., DiNardo, C. D., Dombret, H., Duncavage, E. J., Ebert, B. L., Estey, E. H., Facchetti, F., … Tefferi, A. (2022). International Consensus Classification of myeloid neoplasms and acute leukemias: Integrating morphologic, clinical, and genomic data. Blood, 140(11), 1200–1228. https://doi.org/10.1182/blood.2022015850
Arellano, M. L., Thirman, M. J., DiPersio, J. F., Heiblig, M., Stein, E. M., Schuh, A. C., Žučenka, A., de Botton, S., Grove, C. S., Mannis, G. N., Papayannidis, C., Perl, A. E., Issa, G. C., Aldoss, I., Bajel, A., Dickens, D. S., Kühn, M. W. M., Mantzaris, I., Raffoux, E., … Blachly, J. S. (2025). Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: The AUGMENT-101 study. Blood, 146(9), 1065–1077. https://doi.org/10.1182/blood.2025028357
Baethge, C., Goldbeck-Wood, S., & Mertens, S. (2019). SANRA—a scale for the quality assessment of narrative review articles. Research Integrity and Peer Review, 4, Article 5. https://doi.org/10.1186/s41073-019-0064-8
Badar, T., Luger, S. M., & Litzow, M. R. (2025). Incorporation of immunotherapy into frontline treatment for adults with B-cell precursor acute lymphoblastic leukemia. Blood, 145(14), 1475–1484. https://doi.org/10.1182/blood.2023022921
Badar, T., Szabo, A., Advani, A., Wadleigh, M., Arslan, S., Khan, M. A., Aldoss, I., Siebenaller, C., Schultz, E., Hefazi, M., Shallis, R. M., Yurkiewicz, I., Podoltsev, N., Patel, A. A., Curran, E., Balasubramanian, S., Yang, J., Mattison, R. J., Burkart, M., … Atallah, E. (2020). Real-world outcomes of adult B-cell acute lymphocytic leukemia patients treated with blinatumomab. Blood Advances, 4(10), 2308–2316. https://doi.org/10.1182/bloodadvances.2019001381
Benjamin, R., Graham, C., Yallop, D., Jozwik, A., Mirci-Danicar, O. C., Lucchini, G., Pinner, D., Jain, N., Kantarjian, H., Boissel, N., Maus, M. V., Frigault, M. J., Baruchel, A., Mohty, M., Gianella-Borradori, A., Binlich, F., Balandraud, S., Vitry, F., Thomas, E., … Qasim, W. (2020). Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: Results of two phase 1 studies. The Lancet, 396(10266), 1885–1894. https://doi.org/10.1016/S0140-6736(20)32334-5
Berry, D. A., Zhou, S., Higley, H., Mukundan, L., Fu, S., Reaman, G. H., Wood, B. L., Kelloff, G. J., Jessup, J. M., & Radich, J. P. (2017). Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: A meta-analysis. JAMA Oncology, 3(7), e170580. https://doi.org/10.1001/jamaoncol.2017.0580
Brown, P. A., Ji, L., Xu, X., Devidas, M., Hogan, L. E., Borowitz, M. J., Raetz, E. A., Zugmaier, G., Sharon, E., Bernhardt, M. B., Terezakis, S. A., Gore, L., Whitlock, J. A., Pulsipher, M. A., Hunger, S. P., & Loh, M. L. (2021). Effect of postreinduction therapy consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: A randomized clinical trial. JAMA, 325(9), 833–842. https://doi.org/10.1001/jama.2021.0669
Dunsmore, K. P., Winter, S. S., Devidas, M., Wood, B. L., Esiashvili, N., Chen, Z., Eisenberg, N., Briegel, N., Hayashi, R. J., Gastier-Foster, J. M., Carroll, A. J., Heerema, N. A., Asselin, B. L., Rabin, K. R., Zweidler-McKay, P. A., Raetz, E. A., Loh, M. L., Schultz, K. R., Winick, N. J., … Hunger, S. P. (2020). Children’s Oncology Group AALL0434: A phase III randomized clinical trial testing nelarabine in newly diagnosed T-cell acute lymphoblastic leukemia. Journal of Clinical Oncology, 38(28), 3282–3293. https://doi.org/10.1200/JCO.20.00256
Faham, M., Zheng, J., Moorhead, M., Carlton, V. E. H., Stow, P., Coustan-Smith, E., Pui, C.-H., & Campana, D. (2012). Deep-sequencing approach for minimal residual disease detection in acute lymphoblastic leukemia. Blood, 120(26), 5173–5180. https://doi.org/10.1182/blood-2012-07-444042
Foà, R., Bassan, R., Vitale, A., Elia, L., Piciocchi, A., Puzzolo, M. C., Canichella, M., Viero, P., Ferrara, F., Lunghi, M., Fabbiano, F., Bonifacio, M., Fracchiolla, N., Di Bartolomeo, P., Mancino, A., De Propris, M. S., Vignetti, M., Guarini, A., Rambaldi, A., & Chiaretti, S. (2020). Dasatinib–blinatumomab for Ph-positive acute lymphoblastic leukemia in adults. New England Journal of Medicine, 383(17), 1613–1623. https://doi.org/10.1056/NEJMoa2016272
Gardner, R. A., Finney, O., Annesley, C., Brakke, H., Summers, C., Leger, K., Bleakley, M., Brown, C., Mgebroff, S., Kelly-Spratt, K. S., Hoglund, V., Lindgren, C., Oron, A. P., Li, D., Riddell, S. R., Park, J. R., & Jensen, M. C. (2017). Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood, 129(25), 3322–3331. https://doi.org/10.1182/blood-2017-02-769208
Gökbuget, N., Dombret, H., Bonifacio, M., Reichle, A., Graux, C., Faul, C., Diedrich, H., Topp, M. S., Brüggemann, M., Horst, H.-A., Havelange, V., Stieglmaier, J., Wessels, H., Haddad, V., Benjamin, J. E., Zugmaier, G., Nagorsen, D., & Bargou, R. C. (2018). Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood, 131(14), 1522–1531. https://doi.org/10.1182/blood-2017-08-798322
Grupp, S. A., Maude, S. L., Rives, S., Hiramatsu, H., Baruchel, A., Bader, P., Bittencourt, H., Buechner, J., Laetsch, T. W., De Moerloose, B., Qayed, M., Stefanski, H. E., Davis, K. L., Driscoll, T. A., Nemecek, E., Peters, C., Yanik, G., Balduzzi, A., Boissel, N., … Pulsipher, M. A. (2026). Long-term clinical outcomes of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory ALL. Journal of Clinical Oncology. Advance online publication. https://doi.org/10.1200/JCO-25-01471
Hogan, L. E., Brown, P. A., Ji, L., Xu, X., Devidas, M., Bhatla, T., Borowitz, M. J., Raetz, E. A., Carroll, A., Heerema, N. A., Zugmaier, G., Sharon, E., Bernhardt, M. B., Terezakis, S. A., Gore, L., Whitlock, J. A., Hunger, S. P., & Loh, M. L. (2023). Children’s Oncology Group AALL1331: Phase III trial of blinatumomab in children, adolescents, and young adults with low-risk B-cell ALL in first relapse. Journal of Clinical Oncology, 41(25), 4118–4129. https://doi.org/10.1200/JCO.22.02200
Huguet, F., Leguay, T., Raffoux, E., Thomas, X., Beldjord, K., Delabesse, E., Chevallier, P., Buzyn, A., Delannoy, A., Chalandon, Y., Vernant, J.-P., Lafage-Pochitaloff, M., Chassevent, A., Lhéritier, V., Macintyre, E., Béné, M. C., Ifrah, N., & Dombret, H. (2009). Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: The GRAALL-2003 study. Journal of Clinical Oncology, 27(6), 911–918. https://doi.org/10.1200/JCO.2008.18.6916
Hunger, S. P., & Mullighan, C. G. (2015). Acute lymphoblastic leukemia in children. New England Journal of Medicine, 373(16), 1541–1552. https://doi.org/10.1056/NEJMra1400972
Inaba, H., Greaves, M., & Mullighan, C. G. (2013). Acute lymphoblastic leukaemia. The Lancet, 381(9881), 1943–1955. https://doi.org/10.1016/S0140-6736(12)62187-4
Issa, G. C., Aldoss, I., DiPersio, J., Cuglievan, B., Stone, R., Arellano, M., Thirman, M. J., Patel, M. R., Dickens, D. S., Shenoy, S., Shukla, N., Kantarjian, H., Armstrong, S. A., Perner, F., Perry, J. A., Rosen, G., Bagley, R. G., Meyers, M. L., Ordentlich, P., … Stein, E. M. (2023). The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. Nature, 615(7954), 920–924. https://doi.org/10.1038/s41586-023-05812-3
Issa, G. C., Aldoss, I., Thirman, M. J., DiPersio, J., Arellano, M., Blachly, J. S., Mannis, G. N., Perl, A., Dickens, D. S., McMahon, C. M., Traer, E., Zwaan, C. M., Grove, C. S., Stone, R., Shami, P. J., Mantzaris, I., Greenwood, M., Shukla, N., Cuglievan, B., … Stein, E. M. (2025). Menin inhibition with revumenib for KMT2A-rearranged relapsed or refractory acute leukemia (AUGMENT-101). Journal of Clinical Oncology, 43(1), 75–84. https://doi.org/10.1200/JCO.24.00826
Jabbour, E., Kantarjian, H. M., Aldoss, I., Montesinos, P., Leonard, J. T., Gómez-Almaguer, D., Baer, M. R., Gambacorti-Passerini, C., McCloskey, J., Minami, Y., Papayannidis, C., Rocha, V., Rousselot, P., Vachhani, P., Wang, E. S., Wang, B., Hennessy, M., Vorog, A., Patel, N., … Ribera, J.-M. (2024). Ponatinib vs imatinib in frontline Philadelphia chromosome–positive acute lymphoblastic leukemia: A randomized clinical trial. JAMA, 331(21), 1814–1823. https://doi.org/10.1001/jama.2024.4783
Jabbour, E., Sandhu, K. S., Shaughnessy, P., Logan, A. C., Abedi, M., Shah, B. D., Bishop, M. R., Park, J. H., DeAngelo, D. J., Tholouli, E., Yallop, D., Chaganti, S., Hodby, K., Barba, P., Guerreiro, M., Menne, T., Shang, J., Lao-Sirieix, P., Brugger, W., … Roddie, C. (2026). Tumor burden-guided dosing contributes to mitigation of immunotoxicities following treatment with obecabtagene autoleucel in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia. Haematologica, 111(6), 1999–2010. https://doi.org/10.3324/haematol.2025.288587
Jabbour, E., Short, N. J., Jain, N., Huang, X., Montalban-Bravo, G., Banerjee, P., Rezvani, K., Jiang, X., Kim, K. H., Kanagal-Shamanna, R., Khoury, J. D., Patel, K., Kadia, T. M., Daver, N., Chien, K., Alvarado, Y., Garcia-Manero, G., Issa, G. C., Haddad, F. G., … Kantarjian, H. (2023). Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: A US, single-centre, single-arm, phase 2 trial. The Lancet Haematology, 10(1), e24–e34. https://doi.org/10.1016/S2352-3026(22)00319-2
Jen, W. Y., Jabbour, E., Short, N. J., Issa, G. C., Haddad, F. G., Jain, N., Pemmaraju, N., Daver, N. G., Masarova, L., Borthakur, G., Chien, K., Garris, R., & Kantarjian, H. M. (2024). A phase 2 trial of mini-hyper-CVD, blinatumomab, and ponatinib in Philadelphia positive acute lymphoblastic leukemia. American Journal of Hematology, 99(11), 2229–2232. https://doi.org/10.1002/ajh.27463
Kantarjian, H., Thomas, D., O’Brien, S., Cortes, J., Giles, F., Jeha, S., Bueso-Ramos, C. E., Pierce, S., Shan, J., Koller, C., Beran, M., Keating, M., & Freireich, E. J. (2004). Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer, 101(12), 2788–2801. https://doi.org/10.1002/cncr.20668
Kantarjian, H., Short, N. J., Haddad, F. G., Jain, N., Huang, X., Montalban-Bravo, G., Kanagal-Shamanna, R., Kadia, T. M., Daver, N., Chien, K., Alvarado, Y., Garcia-Manero, G., Issa, G. C., Garris, R., Nasnas, C., Nasr, L., Ravandi, F., & Jabbour, E. (2024). Results of the simultaneous combination of ponatinib and blinatumomab in Philadelphia chromosome-positive ALL. Journal of Clinical Oncology, 42(36), 4246–4251. https://doi.org/10.1200/JCO.24.00272
Kantarjian, H. M., DeAngelo, D. J., Stelljes, M., Martinelli, G., Liedtke, M., Stock, W., Gökbuget, N., O’Brien, S., Wang, K., Wang, T., Paccagnella, M. L., Sleight, B., Vandendries, E., & Advani, A. S. (2016). Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. New England Journal of Medicine, 375(8), 740–753. https://doi.org/10.1056/NEJMoa1509277
Kantarjian, H. M., DeAngelo, D. J., Stelljes, M., Liedtke, M., Stock, W., Gökbuget, N., O’Brien, S. M., Jabbour, E., Wang, T., Liang White, J., Sleight, B., Vandendries, E., & Advani, A. S. (2019). Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: Final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Cancer, 125(14), 2474–2487. https://doi.org/10.1002/cncr.32116
Kantarjian, H., Stein, A., Gökbuget, N., Fielding, A. K., Schuh, A. C., Ribera, J.-M., Wei, A., Dombret, H., Foà, R., Bassan, R., Arslan, Ö., Sanz, M. A., Bergeron, J., Demirkan, F., Lech-Maranda, E., Rambaldi, A., Thomas, X., Horst, H.-A., Brüggemann, M., … Topp, M. S. (2017). Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. New England Journal of Medicine, 376(9), 836–847. https://doi.org/10.1056/NEJMoa1609783
Lee, D. W., Santomasso, B. D., Locke, F. L., Ghobadi, A., Turtle, C. J., Brudno, J. N., Maus, M. V., Park, J. H., Mead, E., Pavletic, S., Go, W. Y., Eldjerou, L., Gardner, R. A., Frey, N., Curran, K. J., Peggs, K., Pasquini, M., DiPersio, J. F., van den Brink, M. R. M., … Neelapu, S. S. (2019). ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biology of Blood and Marrow Transplantation, 25(4), 625–638. https://doi.org/10.1016/j.bbmt.2018.12.758
Litzow, M. R., Sun, Z., Mattison, R. J., Paietta, E. M., Roberts, K. G., Zhang, Y., Racevskis, J., Lazarus, H. M., Rowe, J. M., Arber, D. A., Wieduwilt, M. J., Liedtke, M., Bergeron, J., Wood, B. L., Zhao, Y., Wu, G., Chang, T.-C., Zhang, W., Pratz, K. W., … Tallman, M. S. (2024). Blinatumomab for MRD-negative acute lymphoblastic leukemia in adults. New England Journal of Medicine, 391(4), 320–333. https://doi.org/10.1056/NEJMoa2312948
Malard, F., & Mohty, M. (2020). Acute lymphoblastic leukaemia. The Lancet, 395(10230), 1146–1162. https://doi.org/10.1016/S0140-6736(19)33018-1
Maude, S. L., Laetsch, T. W., Buechner, J., Rives, S., Boyer, M., Bittencourt, H., Bader, P., Verneris, M. R., Stefanski, H. E., Myers, G. D., Qayed, M., De Moerloose, B., Hiramatsu, H., Schlis, K., Davis, K. L., Martin, P. L., Nemecek, E. R., Yanik, G. A., Peters, C., … Grupp, S. A. (2018). Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. New England Journal of Medicine, 378(5), 439–448. https://doi.org/10.1056/NEJMoa1709866
National Comprehensive Cancer Network. (2026). NCCN Clinical Practice Guidelines in Oncology: Acute lymphoblastic leukemia (Version 2.2026). https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1410
O’Brien, M. M., Ji, L., Shah, N. N., Rheingold, S. R., Bhojwani, D., Yuan, C. M., Xu, X., Yi, J. S., Harris, A. C., Brown, P. A., Borowitz, M. J., Militano, O., Kairalla, J., Devidas, M., Raetz, E. A., Gore, L., & Loh, M. L. (2022). Phase II trial of inotuzumab ozogamicin in children and adolescents with relapsed or refractory B-cell acute lymphoblastic leukemia: Children’s Oncology Group protocol AALL1621. Journal of Clinical Oncology, 40(9), 956–967. https://doi.org/10.1200/JCO.21.01693
Pan, J., Tan, Y., Wang, G., Deng, B., Ling, Z., Song, W., Seery, S., Zhang, Y., Peng, S., Xu, J., Duan, J., Wang, Z., Yu, X., Zheng, Q., Xu, X., Yuan, Y., Yan, F., Tian, Z., Tang, K., … Feng, X. (2021). Donor-derived CD7 chimeric antigen receptor T cells for T-cell acute lymphoblastic leukemia: First-in-human, phase I trial. Journal of Clinical Oncology, 39(30), 3340–3351. https://doi.org/10.1200/JCO.21.00389
Park, J. H., Rivière, I., Gonen, M., Wang, X., Sénéchal, B., Curran, K. J., Sauter, C., Wang, Y., Santomasso, B., Mead, E., Roshal, M., Maslak, P., Davila, M., Brentjens, R. J., & Sadelain, M. (2018). Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. New England Journal of Medicine, 378(5), 449–459. https://doi.org/10.1056/NEJMoa1709919
Pasquini, M. C., Hu, Z.-H., Curran, K., Laetsch, T., Locke, F., Rouce, R., Pulsipher, M. A., Phillips, C. L., Keating, A., Frigault, M. J., Salzberg, D., Jaglowski, S., Sasine, J. P., Rosenthal, J., Ghosh, M., Landsburg, D., Margossian, S., Martin, P. L., Kamdar, M. K., … Grupp, S. A. (2020). Real-world evidence of tisagenlecleucel for pediatric acute lymphoblastic leukemia and non-Hodgkin lymphoma. Blood Advances, 4(21), 5414–5424. https://doi.org/10.1182/bloodadvances.2020003092
Pullarkat, V. A., Lacayo, N. J., Jabbour, E., Rubnitz, J. E., Bajel, A., Laetsch, T. W., Leonard, J., Colace, S. I., Khaw, S. L., Fleming, S. A., Mattison, R. J., Norris, R., Opferman, J. T., Roberts, K. G., Zhao, Y., Qu, C., Badawi, M., Schmidt, M., Tong, B., … Stock, W. (2021). Venetoclax and navitoclax in combination with chemotherapy in patients with relapsed or refractory acute lymphoblastic leukemia and lymphoblastic lymphoma. Cancer Discovery, 11(6), 1440–1453. https://doi.org/10.1158/2159-8290.CD-20-1465
Roberts, K. G., Li, Y., Payne-Turner, D., Harvey, R. C., Yang, Y.-L., Pei, D., McCastlain, K., Ding, L., Lu, C., Song, G., Ma, J., Becksfort, J., Rusch, M., Chen, S.-C., Easton, J., Cheng, J., Boggs, K., Santiago-Morales, N., Iacobucci, I., … Mullighan, C. G. (2014). Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. New England Journal of Medicine, 371(11), 1005–1015. https://doi.org/10.1056/NEJMoa1403088
Roddie, C., Sandhu, K. S., Tholouli, E., Logan, A. C., Shaughnessy, P., Barba, P., Ghobadi, A., Guerreiro, M., Yallop, D., Abedi, M., Pantin, J. M., Yared, J. A., Beitinjaneh, A. M., Chaganti, S., Hodby, K., Menne, T., Arellano, M. L., Malladi, R., Shah, B. D., … Jabbour, E. (2024). Obecabtagene autoleucel in adults with B-cell acute lymphoblastic leukemia. New England Journal of Medicine, 391(23), 2219–2230. https://doi.org/10.1056/NEJMoa2406526
Santomasso, B. D., Park, J. H., Salloum, D., Riviere, I., Flynn, J., Mead, E., Halton, E., Wang, X., Senechal, B., Purdon, T., Cross, J. R., Liu, H., Vachha, B., Chen, X., DeAngelis, L. M., Li, D., Bernal, Y., Gonen, M., Wendel, H.-G., … Brentjens, R. J. (2018). Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia. Cancer Discovery, 8(8), 958–971. https://doi.org/10.1158/2159-8290.CD-17-1319
Sasaki, K., Kantarjian, H., Rausch, C. R., Goulart, H., Jain, N., Huang, X., Hachem, M., Wierda, W. G., Kadia, T. M., Borthakur, G., Issa, G. C., Alvarado, Y., Pemmaraju, N., Garris, R., Ravandi, F., Garcia-Manero, G., Short, N. J., & Jabbour, E. (2026). Blinatumomab and ponatinib versus hyper-CVAD and ponatinib in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: A propensity score analysis. American Journal of Hematology, 101(7), 1717–1722. https://doi.org/10.1002/ajh.70325
Shah, B. D., Ghobadi, A., Oluwole, O. O., Logan, A. C., Boissel, N., Cassaday, R. D., Leguay, T., Bishop, M. R., Topp, M. S., Tzachanis, D., O’Dwyer, K. M., Arellano, M. L., Lin, Y., Baer, M. R., Schiller, G. J., Park, J. H., Subklewe, M., Abedi, M., Minnema, M. C., … Houot, R. (2021). 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. The Lancet, 398(10299), 491–502. https://doi.org/10.1016/S0140-6736(21)01222-8
Short, N. J., Kantarjian, H., Furudate, K., Jain, N., Ravandi, F., Karrar, O., Loghavi, S., Nasr, L., Haddad, F. G., Senapati, J., Garris, R., Takahashi, K., & Jabbour, E. (2025). Molecular characterization and predictors of relapse in patients with Ph+ ALL after frontline ponatinib and blinatumomab. Journal of Hematology & Oncology, 18(1), Article 55. https://doi.org/10.1186/s13045-025-01709-y
Siegel, R. L., Kratzer, T. B., Giaquinto, A. N., Sung, H., & Jemal, A. (2025). Cancer statistics, 2025. CA: A Cancer Journal for Clinicians, 75(1), 10–45. https://doi.org/10.3322/caac.21871
Stein, A. S., Kantarjian, H., Gökbuget, N., Bargou, R., Litzow, M. R., Rambaldi, A., Ribera, J. M., Zhang, A., Zimmerman, Z., Zugmaier, G., & Topp, M. S. (2019). Blinatumomab for acute lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation, 25(8), 1498–1504. https://doi.org/10.1016/j.bbmt.2019.04.010
Stock, W., Luger, S. M., Advani, A. S., Yin, J., Harvey, R. C., Mullighan, C. G., Willman, C. L., Fulton, N., Laumann, K. M., Malnassy, G., Paietta, E., Parker, E., Geyer, S., Mrózek, K., Bloomfield, C. D., Sanford, B., Marcucci, G., Liedtke, M., Claxton, D. F., … Larson, R. A. (2019). A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: Results of CALGB 10403. Blood, 133(14), 1548–1559. https://doi.org/10.1182/blood-2018-10-881961
Topp, M. S., Gökbuget, N., Stein, A. S., Zugmaier, G., O’Brien, S., Bargou, R. C., Dombret, H., Fielding, A. K., Heffner, L., Larson, R. A., Neumann, S., Foà, R., Litzow, M., Ribera, J.-M., Rambaldi, A., Schiller, G., Brüggemann, M., Horst, H. A., Holland, C., … Kantarjian, H. (2015). Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: A multicentre, single-arm, phase 2 study. The Lancet Oncology, 16(1), 57–66. https://doi.org/10.1016/S1470-2045(14)71170-2
U.S. Food and Drug Administration. (2017a, August 30). FDA approval brings first gene therapy to the United States [Press release]. https://web.archive.org/web/20250518203136/https://www.fda.gov/news-events/press-announcements/fda-approval-brings-first-gene-therapy-united-states
U.S. Food and Drug Administration. (2017b, August 17). FDA approves inotuzumab ozogamicin for relapsed or refractory B-cell precursor ALL [Approval notification]. https://web.archive.org/web/20260418081121/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-inotuzumab-ozogamicin-relapsed-or-refractory-b-cell-precursor-all
U.S. Food and Drug Administration. (2021, October 1). FDA approves brexucabtagene autoleucel for relapsed or refractory B-cell precursor acute lymphoblastic leukemia [Approval notification]. https://web.archive.org/web/20260203231131/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brexucabtagene-autoleucel-relapsed-or-refractory-b-cell-precursor-acute-lymphoblastic
U.S. Food and Drug Administration. (2024a, June 14). FDA approves blinatumomab as consolidation for CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia [Approval notification]. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-blinatumomab-consolidation-cd19-positive-philadelphia-chromosome-negative-b-cell
U.S. Food and Drug Administration. (2024d, November 15). FDA approves revumenib for relapsed or refractory acute leukemia with a KMT2A translocation [Approval notification]. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-revumenib-relapsed-or-refractory-acute-leukemia-kmt2a-translocation
U.S. Food and Drug Administration. (2024c, November 8). FDA approves obecabtagene autoleucel for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia [Approval notification]. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-obecabtagene-autoleucel-adults-relapsed-or-refractory-b-cell-precursor-acute
van Dongen, J. J. M., van der Velden, V. H. J., Brüggemann, M., & Orfao, A. (2015). Minimal residual disease diagnostics in acute lymphoblastic leukemia: Need for sensitive, fast, and standardized technologies. Blood, 125(26), 3996–4009. https://doi.org/10.1182/blood-2015-03-580027
von Stackelberg, A., Locatelli, F., Zugmaier, G., Handgretinger, R., Trippett, T. M., Rizzari, C., Bader, P., O’Brien, M. M., Brethon, B., Bhojwani, D., Schlegel, P. G., Borkhardt, A., Rheingold, S. R., Cooper, T. M., Zwaan, C. M., Barnette, P., Messina, C., Michel, G., DuBois, S. G., … Gore, L. (2016). Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. Journal of Clinical Oncology, 34(36), 4381–4389. https://doi.org/10.1200/JCO.2016.67.3301
Gökbuget, N., Boissel, N., Chiaretti, S., Dombret, H., Doubek, M., Fielding, A., Foà, R., Giebel, S., Hoelzer, D., Hunault, M., Marks, D. I., Martinelli, G., Ottmann, O., Rijneveld, A., Rousselot, P., Ribera, J., & Bassan, R. (2024). Diagnosis, prognostic factors, and assessment of ALL in adults: 2024 ELN recommendations from a European expert panel. Blood, 143(19), 1891–1902. https://doi.org/10.1182/blood.2023020794
Gökbuget, N., Boissel, N., Chiaretti, S., Dombret, H., Doubek, M., Fielding, A., Foà, R., Giebel, S., Hoelzer, D., Hunault, M., Marks, D. I., Martinelli, G., Ottmann, O., Rijneveld, A., Rousselot, P., Ribera, J., & Bassan, R. (2024). Management of ALL in adults: 2024 ELN recommendations from a European expert panel. Blood, 143(19), 1903–1930. https://doi.org/10.1182/blood.2023023568
U.S. Food and Drug Administration. (2018, March 29). FDA expands approval of Blincyto for treatment of a type of leukemia in patients who have a certain risk factor for relapse [Press release]. https://www.fda.gov/news-events/press-announcements/fda-expands-approval-blincyto-treatment-type-leukemia-patients-who-have-certain-risk-factor-relapse
U.S. Food and Drug Administration. (2024b, March 6). FDA approves inotuzumab ozogamicin for pediatric patients with acute lymphoblastic leukemia [Approval notification]. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-inotuzumab-ozogamicin-pediatric-patients-acute-lymphoblastic-leukemia
U.S. Food and Drug Administration. (2024e, March 19). FDA grants accelerated approval to ponatinib with chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia [Approval notification]. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-ponatinib-chemotherapy-newly-diagnosed-philadelphia-chromosome
U.S. Food and Drug Administration. (2005). Arranon (nelarabine) NDA 21-877 approval documentation. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021877_s000_Arranon_Approv.pdf
Short, N. J., Aldoss, I., DeAngelo, D. J., Konopleva, M., Leonard, J., Logan, A. C., Park, J., Shah, B., Stock, W., & Jabbour, E. (2025). Clinical use of measurable residual disease in adult ALL: Recommendations from a panel of US experts. Blood Advances, 9(6), 1442–1451. https://doi.org/10.1182/bloodadvances.2024015441
Reiterová, M., Kohlscheen, S., Maglia, O., Sala, S., Schumich, A., Maurer-Granofszky, M., Faggin, G., Scarparo, P., Varotto, E., Šestáková, Z., Švec, P., Feuerstein, T., Vernitsky, H., Kužílková, D., Hrušák, O., Buldini, B., Dworzak, M., Brüggemann, M., Gaipa, G., & Kalina, T. (2025). Flow-cytometric MRD detection in pediatric T-ALL: A multicenter AIEOP-BFM consensus-based guided standardized approach. Clinical Chemistry and Laboratory Medicine, 63(7), 1419–1426. https://doi.org/10.1515/cclm-2024-1503
Jabbour, E., Lussana, F., Martínez-Sánchez, P., Torrent, A., Rifón, J. J., Agrawal, V., Tormo, M., Cassaday, R. D., Cluzeau, T., Huguet, F., Papayannidis, C., Hernández-Rivas, J. M., Rijneveld, A., Fleming, S., Vucinic, V., Böll, B., Ikezoe, T., Abdul-Hay, M., Savoie, M. L., … Kantarjian, H. (2025). Subcutaneous blinatumomab in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: Post-hoc safety and activity analysis from a multicentre, single-arm, phase 1/2 trial. The Lancet Haematology, 12(7), e529–e541. https://doi.org/10.1016/S2352-3026(25)00144-9
Chiaretti, S., Di Trani, M., Skert, C., Elia, L., Almici, G., Della Starza, I., Cardinali, D., Bellomarino, V., Soddu, S., Messina, M., Marino, M. R., De Propris, M. S., Borlenghi, E., Di Raimondo, F., Ansuinelli, M., Alati, C., Mattei, D. G., Mancini, V., Chiusolo, P., … Foà, R. (2025). First results of the phase III GIMEMA ALL2820 trial comparing ponatinib plus blinatumomab to imatinib and chemotherapy for newly diagnosed adult Ph+ acute lymphoblastic leukemia [Abstract 439]. Blood, 146(Suppl. 1), 439. https://doi.org/10.1182/blood-2025-439
Santomasso, B. D., Nastoupil, L. J., Adkins, S., Lacchetti, C., Schneider, B. J., Anadkat, M., Atkins, M. B., Brassil, K. J., Caterino, J. M., Chau, I., Davies, M. J., Ernstoff, M. S., Fecher, L., Funchain, P., Jaiyesimi, I., Mammen, J. S., Naidoo, J., Naing, A., Phillips, T., … Ghosh, M. (2021). Management of immune-related adverse events in patients treated with chimeric antigen receptor T-cell therapy: ASCO guideline. Journal of Clinical Oncology, 39(35), 3978–3992. https://doi.org/10.1200/JCO.21.01992
Zhao, L., Li, C., Zuo, S., Han, Y., Deng, B., Ling, Z., Zhang, Y., Peng, S., Xu, J., Duan, J., Wang, Z., Yu, X., Zheng, Q., Xu, X., Yuan, Y., Tian, Z., Tang, K., Zhang, Y., Niu, Q., … Pan, J. (2025). Autologous CD7 CAR-T cells generated without T cell pre-selection in pediatric patients with relapsed/refractory T-ALL: A phase I trial. Molecular Therapy, 33(6), 2753–2767. https://doi.org/10.1016/j.ymthe.2024.09.006
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Copyright (c) 2026 Karolina Skórka, Oliwia Żmuda, Natalia Skórka, Anna Halot, Patrycja Walo, Klaudia Wydra, Jakub Jakubiec, Michał Szubartowski, Adam Szymczyk, Magdalena Tatara
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