OUTCOMES OF BLINATUMOMAB THE INITIAL PHASE OF CHEMOTHERAPY IN CHILDREN WITH B-CELL ALL
Keywords:
ALL, blinatumomab, minimal residual disease, childrenAbstract
This retrospective single‑center study (2020–2024) from the Pediatric Oncology Center in Tashkent evaluated the efficacy of incorporating blinatumomab (14‑day courses at 15 μg/m²/day, twice with a two‑month interval) into the ALL‑MB‑2015 protocol for children with B‑cell ALL who remained MRD‑positive post‑induction. All 25 patients achieved hematologic remission; MRD dropped from 12 % to 0.001 % after the first blinatumomab course, and remained negative after the second. Median follow‑up was 2.5 years. There were two late relapses (in standard‑ and intermediate‑risk groups), 4‑year EFS was 88.1 ± 3.7 %, and no deaths occurred. Adverse events (allergic reactions, neurotoxicity, hypoalbuminemia, cytopenias) were manageable.
References
Queudeville, M.; Ebinger, M. Blinatumomab in Pediatric Acute Lymphoblastic Leukemia—From Salvage to First Line Therapy (A Systematic Review). J. Clin. Med. 2021, 10, 2544. https://doi.org/ 10.3390/jcm10122544
Shukla, N.; Sulis, M.L. Blinatumomab for Treatment of Children With High-risk Relapsed B-Cell Acute Lymphoblastic Leukemia. JAMA 2021, 325, 830–832.
Inaba, H.; Pui, C.H. Immunotherapy in pediatric acute lymphoblastic leukemia. Cancer Metastasis Rev. 2019, 38, 595–610.
Foster, J.B.; Maude, S.L. New developments in immunotherapy for pediatric leukemia. Curr. Opin. Pediatr. 2018, 30, 25–29.
Bautista, F.; Van der Lugt, J.; Kearns, P.R.; Mussai, F.J.; Zwaan, C.M.; Moreno, L. The development of targeted new agents to improve the outcome for children with leukemia. Expert Opin. Drug Discov. 2016, 11, 1111–1122.
Jasinski, S.; De Los Reyes, F.A.; Yametti, G.C.; Pierro, J.; Raetz, E.; Carroll, W.L. Immunotherapy in Pediatric B-Cell Acute Lymphoblastic Leukemia: Advances and Ongoing Challenges. Paediatr. Drugs 2020, 22, 485–499.
von Stackelberg, A.; Locatelli, F.; Zugmaier, G.; Handgretinger, R.; Trippett, T.M.; Rizzari, C.; Bader, P.; O’Brien, M.M.; Brethon, B.; Bhojwani, D.; et al. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. J. Clin. Oncol. 2016, 34, 4381–4389.
Gore, L.; Locatelli, F.; Zugmaier, G.; Handgretinger, R.; O’Brien, M.M.; Bader, P.; Bhojwani, D.; Schlegel, P.G.; Tuglus, C.A.; von Stackelberg, A. Survival after blinatumomab treatment in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Blood Cancer J. 2018, 8, 80. [PubMed] J. Clin. Med. 2021, 10, 2544.
Brown, P.A.; Ji, L.; Xu, X.; Devidas, M.; Hogan, L.; Borowitz, M.J.; Raetz, E.A.; Zugmaier, G.; Sharon, E.; Gore, L.; et al. A Randomized Phase 3 Trial of Blinatumomab Vs. Chemotherapy As Post-Reinduction Therapy in High and Intermediate Risk (HR/IR) First Relapse of B-Acute Lymphoblastic Leukemia (B-ALL) in Children and Adolescents/Young Adults (AYAs) Demonstrates Superior Efficacy and Tolerability of Blinatumomab: A Report from Children’s Oncology Group Study AALL1331. Blood 2019, 134, LBA-1.
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.; et al. 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 2021, 325, 833–842
Locatelli, F.; Zugmaier, G.; Rizzari, C.; Morris, J.D.; Gruhn, B.; Klingebiel, T.; Parasole, R.; Linderkamp, C.; Flotho, C.; Petit, A.; et al. Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA 2021, 325, 843–854.
Schlegel, P.; Lang, P.; Zugmaier, G.; Ebinger, M.; Kreyenberg, H.; Witte, K.E.; Feucht, J.; Pfeiffer, M.; Teltschik, H.M.; Kyzirakos, C.; et al. Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab. Haematologica 2014, 99, 1212–1219.
Pieters, R.; De Lorenzo, P.; Ancliffe, P.; Aversa, L.A.; Brethon, B.; Biondi, A.; Campbell, M.; Escherich, G.; Ferster, A.; Gardner, R.A.; et al. Outcome of Infants Younger Than 1 Year With Acute Lymphoblastic Leukemia Treated With the Interfant-06 Protocol: Results From an International Phase III Randomized Study. J. Clin. Oncol. 2019, 37, 2246–2256.
Mikhailova EV, Illarionova OI, Maschan MA, et al. Guidelines for monitoring minimal residual disease by flow cytometry in B-cell acute lymphoblastic leukemia after CD19-targeted immunotherapy. Pediatr Hematol/Oncol Immunopathol 2023;22:175–84. 10.24287/1726-1708-2023-22-2-175-184
Popov A, Henze G, Rumyantseva J, et al. A simple procedure for identifying children with B-cell lineage acute lymphoblastic leukemia who can be successfully treated with low- or intermediate-intensity drugs: sequential and single-point measurement of minimal residual disease. Pediatr Blood Cancer 2023;70:e30295. 10.1002/pbc.30295
Popov A, Henze G, Rumyantseva J, et al. Flow cytometric determination of minimal residual mass (MRM) at the end of consolidation in pediatric B-cell acute lymphoblastic leukemia has important prognostic value but limited clinical significance: results from the ALL-MB 2008 study. Leuk Res 2023;125. 10.1016/j.leukres.2022.106998
Alkhathami, A. G., Altalbawy, F. M. A., Rizaev, J. A., Jeddoa, Z. M. A., & Jabir, M. S. (2025). An overview of lncRNA GAPLINC's role in human cancer growth and metastasis. Archives of Biochemistry and Biophysics, 110506.
Irgashev, K. N., & Rizaev, J. A. (2025). Optimization of clinical outcomes in the rehabilitation of patients with non-caries dental lesions manifesting as pathological abrasion. Medical Research Journal, 1(1), 146–151.
Shakhanova, S. S., Abdurakhmonov, J. A., & Rakhimov, N. M. (2023). Targeted therapy in the palliative treatment of platinum-resistant recurrent ovarian cancer complicated by ascites. The American Journal of Medical Sciences and Pharmaceutical Research, 5(8), 1.
Rizaev, J. A., Rahimov, N. M., & Shakhanova, S. S. (2023). Prostate cancer morbidity and mortality among men in high-risk areas. Eurasian Medical Research Periodical, 18, 101–104.
