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DOI: 10.1055/s-0045-1809167
FLAG with Bortezomib in Children and Adolescents with Relapsed/Refractory Acute Myeloid Leukemia in a Resource-Limited Setting: A Single-Center Experience from India
Authors
Abstract
Objectives
The present study aimed to evaluate the impact, challenges, and outcome by adding bortezomib to the FLAG (fludarabine, cytarabine, and filgrastim) regimen in these populations in a resource-constraint setting.
Materials and Methods
A prospective observational study was conducted at a tertiary cancer center in India from January 2022 to September 2024 involving patients diagnosed with relapsed/refractory acute myeloid leukemia (AML) receiving FLAG-bortezomib. Complete remission (CR) and associated toxicities were assessed.
Results
Out of 13 patients, 8 (61.53%) were males and 5 (38.46%) were females (range: 2–17 years). Sorafenib (n = 1) and midostaurin (n = 2) were given along with chemotherapy for children with FLT3 mutations. Myelosuppression was the most frequent toxicity, with all patients developing ≥ grade 3 pancytopenia. Five (38.46%) patients achieved CR after first cycle, two (15.39%) died during treatment, and six (46.15%) were with persistent leukemic activity. Median duration of neutrophil and platelet recovery was 22 (range: 6–65) and 24 (range: 5–70) days, respectively, in children who achieved CR. Median overall survival was 12 months. At the last follow-up, three (23.08%) patients are alive.
Conclusion
FLAG-bortezomib regimen could help in pediatric and adolescent relapsed AML to achieve a remission comparable with other regimen in low- and middle-income countries, highlighting its potential.
Keywords
FLAG-bortezomib - pediatric AML - pediatric oncology - relapsed/refractory AML - salvage chemotherapy of relapsed AMLAuthors' Contributions
D.D., H.T., and M.T. contributed to the concept and design of the study, as well as the acquisition, analysis, and interpretation of data. The manuscript was drafted by D.D., M.T., R.Y., and C.D., along with participation in the critical review for important intellectual content. Supervision of the study was provided by M.T. and H.P.
Financial Disclosures
None.
Publication History
Received: 14 February 2025
Accepted: 18 April 2025
Article published online:
15 May 2025
© 2025. MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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References
- 1 Egan G, Tasian SK. Relapsed pediatric acute myeloid leukaemia: state-of-the-art in 2023. Haematologica 2023; 108 (09) 2275-2288
- 2 Fleischhack G, Hasan C, Graf N, Mann G, Bode U. IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF), an effective remission-induction therapy for poor-prognosis AML of childhood prior to allogeneic or autologous bone marrow transplantation: experiences of a phase II trial. Br J Haematol 1998; 102 (03) 647-655
- 3 Ravichandran N, Uppuluri R, Swaminathan VV. et al. FLAG with bortezomib in childhood relapsed/refractory leukemia: remission induction with limited toxicity in the era of multidrug-resistant bacteria. J Pediatr Hematol Oncol 2021; 43 (02) e212-e214
- 4 Farooq MU, Mushtaq F, Farooq A, Khan DH, Mir MA. FLAG vs FLAG-IDA: outcomes in relapsed/refractory acute leukemias. Cancer Chemother Pharmacol 2019; 83 (06) 1191-1193
- 5 Srinivasan S, Gollamudi VRM, Dhariwal N. Pediatric acute myeloid leukemia in India: a systematic review. Indian J Med Paediatr Oncol 2022; 43 (04) 342-348
- 6 Horton TM, Perentesis JP, Gamis AS. et al. A phase 2 study of bortezomib combined with either idarubicin/cytarabine or cytarabine/etoposide in children with relapsed, refractory or secondary acute myeloid leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer 2014; 61 (10) 1754-1760
- 7 Yılmaz Bengoa Ş, Ataseven E, Kızmazoğlu D, Demir Yenigürbüz F, Erdem M, Ören H. FLAG regimen with or without idarubicin in children with relapsed/refractory acute leukemia: experience from a Turkish pediatric hematology center. Turk J Haematol 2017; 34 (01) 46-51
- 8 Cherulil SJ, Melarcode Ramanan K, Gangadharan KV. et al. FLAG with bortezomib salvage therapy in relapsed/refractory childhood leukemia-a reliable bridge to transplantation with limited toxicity. South Asian J Cancer 2024;
- 9 Lonetti A, Pession A, Masetti R. Targeted therapies for pediatric AML: gaps and perspective. Front Pediatr 2019; 7: 463
