FLAG-Ida’ya Karşı FLAG-Dauno: Relaps/Refrakter Akut Lösemi Olgularında Bursa Uludağ Üniversitesi Deneyimi
Abstract
FLAG-Ida protokolü (Fludarabin- Sitarabin- Granülosit Koloni Stimülan Faktör- İdarubisin) relaps/refrakter akut lösemi olgularında sıklıkla uygulanan bir kemoterapi rejimidir. Özellikle ilaç erişiminde olan aksaklıklar nedeniyle, antrasiklin ajan olarak idarubisin yerine daunorubisin kullanılabilmektedir. Çalışmamızda, Bursa Uludağ Üniversitesi Hematoloji kliniğinde relaps/refrakter akut lösemi tanısı ile FLAG-Ida ya da FLAG-Dauno protokolü alan hastaların etkinlik ve yan etki verilerini değerlendirmeyi amaçladık. Çalışmaya toplam 94 hasta dahil edildi. On hasta FLAG-Dauno grubunda iken 84 hasta FLAG-Ida grubundaydı. Çalışma grubunun medyan yaşı 46.5 yıldı. Hastaların %45.7’si Akut Myeloid Lösemi (AML), %54.3’ü Akut Lenfoblastik Lösemi (ALL) tanılıydı. Hasta karekteristikleri, sitogenetik risk profilleri, primer tanıları ve primer refrakter hastalık varlığı açısından FLAG-Ida ve FLAG-Dauno grupları arasında anlamlı farklılık yoktu. İki grupta da komplet yanıt oranı ve allojeneik nakle köprülenen hasta sayıları benzer orandaydı. Toplam yaşam süreleri açısından iki grup arasında anlamlı farklılık saptanmadı. İki grup arasında yan etki karşılaştırmasında; iki grupta da en sık görülen rejim ilişkili toksisite febril nötropeniydi. Grade 3-4 yan etkiler açısından iki grup arasında anlamlı farklılık saptanmadı. Sonuç olarak FLAG-Dauno protokolü relaps/refrakter akut lösemi olgularında etkin ve güvenli bir kurtarma rejimidir.
Keywords
References
- 1. Döhner, H., Weisdorf, D. J. & Bloomfield, C. D. Acute Myeloid Leukemia. New England Journal of Medicine 373, 1136–1152 (2015).
- 2. Sedov, V. & Stuart, R. K. Vosaroxin in relapsed/refractory acute myeloid leukemia: efficacy and safety in the context of the current treatment landscape. Ther Adv Hematol 8, 185–195 (2017).
- 3. Mohty, M. et al. Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia. Haematologica 102, 184–191 (2017).
- 4. Estey, E. Why are there so few randomized trials for patients with primary refractory acute myeloid leukemia? Best Pract Res Clin Haematol 29, 324–328 (2016).
- 5. Bose, P., Vachhani, P. & Cortes, J. E. Treatment of Relapsed/Refractory Acute Myeloid Leukemia. Curr Treat Options Oncol 18, 1–30 (2017).
- 6. Thiel, A. et al. Mito-FLAG with Ara-C as bolus versus continuous infusion in recurrent or refractory AML—long-term results of a prospective randomized intergroup study of the East German Study Group Hematology/Oncology (OSHO) and the Study Alliance Leukemia (SAL). Annals of Oncology 26, 1434–1440 (2015).
- 7. [The guidelines for diagnosis and treatment of acute myelogenous leukemia (relapse/refractory) in China (2017)]. Zhonghua Xue Ye Xue Za Zhi 38, 183–184 (2017).
- 8. Parker, J. E. et al. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol 99, 939–944 (1997).
- 9. Delia, M. et al. FLAG-Ida Regimen as Bridge Therapy to Allotransplantation in Refractory/Relapsed Acute Myeloid Leukemia Patients. Clin Lymphoma Myeloma Leuk 17, 767–773 (2017).
- 10. Atra, A. et al. Outcome of relapsed or refractory childhood B-cell acute lymphoblastic leukaemia and B-cell non-Hodgkin’s lymphoma treated with the UKCCSG 9003/9002 protocols. Br J Haematol 112, 965–968 (2001).
- 11. Freund, M. et al. Treatment of relapsed acute lymphocytic leukemia in adults. Haematol Blood Transfus 33, 432–436 (1990).
- 12. Martino, R. et al. Allogeneic or autologous stem cell transplantation following salvage chemotherapy for adults with refractory or relapsed acute lymphoblastic leukemia. Bone Marrow Transplant 21, 1023–1027 (1998).
- 13. Pastore, D. et al. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol 82, 231–235 (2003).
- 14. Estey, E. et al. Use of granulocyte colony-stimulating factor before, during, and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine plus cytarabine without granulocyte colony-stimulating factor. J Clin Oncol 12, 671–678 (1994).
- 15. Schmitt, B. et al. Fludarabine combination therapy for the treatment of chronic lymphocytic leukemia. Clin Lymphoma 3, 26–35 (2002).
- 16. Samra, B. et al. Outcome of adults with relapsed/refractory T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Am J Hematol 95, E245–E247 (2020).
- 17. Mandelli, F. et al. A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia. A multicentric study from the Italian Co-operative Group GIMEMA. Eur J Cancer 27, 750–755 (1991).
- 18. Vogler, W. R. et al. A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group Study. J Clin Oncol 10, 1103–1111 (1992).
- 19. Lee, J. H. et al. A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia. Blood 118, 3832–3841 (2011).
- 20. Wang, J. et al. Meta-Analysis of Randomised Clinical Trials Comparing Idarubicin + Cytarabine with Daunorubicin + Cytarabine as the Induction Chemotherapy in Patients with Newly Diagnosed Acute Myeloid Leukaemia. doi:10.1371/journal.pone.0060699.
- 21. Wang, H., Xiao, X., Xiao, Q., Lu, Y. & Wu, Y. The efficacy and safety of daunorubicin versus idarubicin combined with cytarabine for induction therapy in acute myeloid leukemia: A meta-analysis of randomized clinical trials. Medicine 99, E20094 (2020).
- 22. Mandelli, F. et al. Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10. J Clin Oncol 27, 5397–5403 (2009).
- 23. Adige, S. et al. Equipotent doses of daunorubicin and idarubicin for AML: a meta-analysis of clinical trials versus in vitro estimation. Cancer Chemother Pharmacol 83, 1105–1112 (2019).
- 24. Children’s Oncology Group. Long-term Follow-up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer. 2013;4:http://www.survivorshipguidelines.org/pdf/ LTFUGuidelines_40.pdf.
- 25. Russell, N. H. et al. A randomised comparison of FLAG-Ida versus daunorubicin combined with clofarabine in relapsed orrefractory acute myeloid leukaemia: Results from the UK NCRI AML17 trial. Br J Haematol 198, 528–534 (2022).
- 26. Mushtaq MU, Harrington AM, Chaudhary SG, Michaelis LC,Carlson KB, Abedin S, Runass L, Callander NS, Fallon MJ,Juckett M, Hall AC, Hematti P, Mattison RJ, Atallah EL, GuruMurthy GS. Comparison of salvage chemotherapy regimens and prognostic significance of minimal residual disease in relapsed/refractory acute myeloid leukemia. Leuk Lymphoma. 2021 Jan;62(1):158-166
FLAG-Dauno vs FLAG-Ida: Bursa Uludağ University Experience in Relaps/Refractory Acute Leukemia Cases
Abstract
FLAG-Ida protocol (Fludarabine- Cytarabine- Granulocyte Colony Stimulating Factor- Idarubicin) is a chemotherapy regimen frequently used in relapsed/refractory acute leukemia cases. Daunorubicin can be used instead of idarubicin as an anthracycline agent, especially due to problems in drug access. In our study, we aimed to evaluate the efficacy and side effect data of patients with relapsed/refractory acute leukemia who received FLAG-Ida or FLAG-Dauno protocol in the haematology clinic of Bursa Uludag University. A total of 94 patients were included in the study. Ten patients were in the FLAG-Dauno group and 84 patients were in the FLAG-Ida group. The median age of the study group was 46.5 years. Acute Myeloid Leukemia (AML) was diagnosed in 45.7% and Acute Lymphoblastic Leukemia (ALL) in 54.3% of the patients. There was no significant difference between FLAG-Ida and FLAG-Dauno groups in terms of patient characteristics, cytogenetic risk profiles, primary diagnoses and presence of primary refractory disease. Complete response rate and the number of patients bridged to allogeneic transplantation were similar in both groups. There was no significant difference in total survival between the two groups. In the side effect comparison between the two groups, the most common regimen-related toxicity in both groups was febrile neutropenia. No significant difference was found between the two groups in terms of Grade 3-4 side effects. In conclusion, FLAG-Dauno protocol is an effective and safe salvage regimen in relapsed/refractory acute leukaemia patients.
Keywords
References
- 1. Döhner, H., Weisdorf, D. J. & Bloomfield, C. D. Acute Myeloid Leukemia. New England Journal of Medicine 373, 1136–1152 (2015).
- 2. Sedov, V. & Stuart, R. K. Vosaroxin in relapsed/refractory acute myeloid leukemia: efficacy and safety in the context of the current treatment landscape. Ther Adv Hematol 8, 185–195 (2017).
- 3. Mohty, M. et al. Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia. Haematologica 102, 184–191 (2017).
- 4. Estey, E. Why are there so few randomized trials for patients with primary refractory acute myeloid leukemia? Best Pract Res Clin Haematol 29, 324–328 (2016).
- 5. Bose, P., Vachhani, P. & Cortes, J. E. Treatment of Relapsed/Refractory Acute Myeloid Leukemia. Curr Treat Options Oncol 18, 1–30 (2017).
- 6. Thiel, A. et al. Mito-FLAG with Ara-C as bolus versus continuous infusion in recurrent or refractory AML—long-term results of a prospective randomized intergroup study of the East German Study Group Hematology/Oncology (OSHO) and the Study Alliance Leukemia (SAL). Annals of Oncology 26, 1434–1440 (2015).
- 7. [The guidelines for diagnosis and treatment of acute myelogenous leukemia (relapse/refractory) in China (2017)]. Zhonghua Xue Ye Xue Za Zhi 38, 183–184 (2017).
- 8. Parker, J. E. et al. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol 99, 939–944 (1997).
- 9. Delia, M. et al. FLAG-Ida Regimen as Bridge Therapy to Allotransplantation in Refractory/Relapsed Acute Myeloid Leukemia Patients. Clin Lymphoma Myeloma Leuk 17, 767–773 (2017).
- 10. Atra, A. et al. Outcome of relapsed or refractory childhood B-cell acute lymphoblastic leukaemia and B-cell non-Hodgkin’s lymphoma treated with the UKCCSG 9003/9002 protocols. Br J Haematol 112, 965–968 (2001).
- 11. Freund, M. et al. Treatment of relapsed acute lymphocytic leukemia in adults. Haematol Blood Transfus 33, 432–436 (1990).
- 12. Martino, R. et al. Allogeneic or autologous stem cell transplantation following salvage chemotherapy for adults with refractory or relapsed acute lymphoblastic leukemia. Bone Marrow Transplant 21, 1023–1027 (1998).
- 13. Pastore, D. et al. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol 82, 231–235 (2003).
- 14. Estey, E. et al. Use of granulocyte colony-stimulating factor before, during, and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine plus cytarabine without granulocyte colony-stimulating factor. J Clin Oncol 12, 671–678 (1994).
- 15. Schmitt, B. et al. Fludarabine combination therapy for the treatment of chronic lymphocytic leukemia. Clin Lymphoma 3, 26–35 (2002).
- 16. Samra, B. et al. Outcome of adults with relapsed/refractory T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Am J Hematol 95, E245–E247 (2020).
- 17. Mandelli, F. et al. A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia. A multicentric study from the Italian Co-operative Group GIMEMA. Eur J Cancer 27, 750–755 (1991).
- 18. Vogler, W. R. et al. A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group Study. J Clin Oncol 10, 1103–1111 (1992).
- 19. Lee, J. H. et al. A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia. Blood 118, 3832–3841 (2011).
- 20. Wang, J. et al. Meta-Analysis of Randomised Clinical Trials Comparing Idarubicin + Cytarabine with Daunorubicin + Cytarabine as the Induction Chemotherapy in Patients with Newly Diagnosed Acute Myeloid Leukaemia. doi:10.1371/journal.pone.0060699.
- 21. Wang, H., Xiao, X., Xiao, Q., Lu, Y. & Wu, Y. The efficacy and safety of daunorubicin versus idarubicin combined with cytarabine for induction therapy in acute myeloid leukemia: A meta-analysis of randomized clinical trials. Medicine 99, E20094 (2020).
- 22. Mandelli, F. et al. Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10. J Clin Oncol 27, 5397–5403 (2009).
- 23. Adige, S. et al. Equipotent doses of daunorubicin and idarubicin for AML: a meta-analysis of clinical trials versus in vitro estimation. Cancer Chemother Pharmacol 83, 1105–1112 (2019).
- 24. Children’s Oncology Group. Long-term Follow-up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer. 2013;4:http://www.survivorshipguidelines.org/pdf/ LTFUGuidelines_40.pdf.
- 25. Russell, N. H. et al. A randomised comparison of FLAG-Ida versus daunorubicin combined with clofarabine in relapsed orrefractory acute myeloid leukaemia: Results from the UK NCRI AML17 trial. Br J Haematol 198, 528–534 (2022).
- 26. Mushtaq MU, Harrington AM, Chaudhary SG, Michaelis LC,Carlson KB, Abedin S, Runass L, Callander NS, Fallon MJ,Juckett M, Hall AC, Hematti P, Mattison RJ, Atallah EL, GuruMurthy GS. Comparison of salvage chemotherapy regimens and prognostic significance of minimal residual disease in relapsed/refractory acute myeloid leukemia. Leuk Lymphoma. 2021 Jan;62(1):158-166
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Haematology |
| Journal Section | Research Article |
| Authors | |
| Publication Date | May 17, 2024 |
| Submission Date | February 1, 2024 |
| Acceptance Date | April 3, 2024 |
| Published in Issue | Year 2024 Volume: 50 Issue: 1 |
Cite
Journal of Uludag University Medical Faculty is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.