Evaluation of Efficacy, Safety, and Prognostic Value of Induction Chemotherapy in Patients with Acute Myeloid Leukemia: An Updated Meta-Analysis of a 5-Year Study
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Abstract
Acute Myeloid Leukemia (AML) is a type of cancer that affects the bone marrow and blood. This study aims to conduct a five-year update on induction chemotherapy's efficacy, safety, and prognostic value in patients with AML.
Based on the PRISMA 2020 guidelines, a systematic search was performed on online databases for relevant studies on complete remission with incomplete hematologic response (CRi), complete remission (CR), adverse events, and overall survival. The articles obtained were observational studies that met the inclusion and exclusion criteria. The quality of the studies was assessed using the Revised Cochrane’s risk-of-bias tool. The analysis was conducted using Review Manager 5.4 and R Statistical Software 3.3.
Thirteen clinical trial studies, involving 1,863 participants, were included in this survey. Based on the analysis, the CRi and CR levels, where each was obtained as a whole at 9% (random effect; 95%CI 6-13%; heterogeneity;
1. Pelcovits A, Niroula R. Acute Myeloid Leukemia: A Review. R I Med J (2013). 2020;103(3):38–40.
2. Shimony S, Stahl M, Stone RM. Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023;98(3):502–26.
3. Jani CT, Ahmed A, Singh H, et al. Burden of AML, 1990-2019: Estimates From the Global Burden of Disease Study. JCO Glob Oncol. 2023;(9): e2300229.
4. Adige S, Lapidus RG, Carter-Cooper BA, et al. Equipotent doses of daunorubicin and idarubicin for AML: a meta-analysis of clinical trials versus in vitro estimation. Cancer Chemother Pharmacol. 2019;83(6):1105–12.
5. Cortes JE, Lin TL, Asubonteng K, et al. Efficacy and safety of CPX-351 versus 7 + 3 chemotherapy by European LeukemiaNet 2017 risk subgroups in older adults with newly diagnosed, high-risk/secondary AML: post hoc analysis of a randomized, phase 3 trial. J Hematol Oncol. 2022;15(1):155.
6. Ferrero D, Crisà E, Marmont F, et al. Survival improvement of poor-prognosis AML/MDS patients by maintenance treatment with low-dose chemotherapy and differentiating agents. Ann Hematol. 2014;93(8):1391–400.
7. Gill H, Yim R, Pang HH, et al. Clofarabine, cytarabine, and mitoxantrone in refractory/relapsed acute myeloid leukemia: High response rates and effective bridge to allogeneic hematopoietic stem cell transplantation. Cancer Med. 2020;9(10):3371–82.
8. Guolo F, Fianchi L, Minetto P, et al. CPX-351 treatment in secondary acute myeloblastic leukemia is effective and improves the feasibility of allogeneic stem cell transplantation: results of the Italian compassionate use program. Blood Cancer J. 2020;10(10):96.
9. Issa GC, Kantarjian HM, Xiao L, et al. Phase II trial of CPX-351 in patients with acute myeloid leukemia at high risk for induction mortality. Leukemia. 2020;34(11):2914–24.
10. Kadia TM, Reville PK, Borthakur G, et al. Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a cohort from a single-centre, single-arm, phase 2 trial. Lancet Haematol. 2021;8(8):e552–e561.
11. Muresan B, Mamolo C, Cappelleri JC, et al. Comparing cure rates for gemtuzumab ozogamicin plus standard chemotherapy vs standard chemotherapy alone in acute myeloid leukemia patients. Futur Oncol. 2021;17(22):2883–92.
12. Ravandi F, Assi R, Daver N, et al. Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a single-arm, phase 2 study. Lancet Haematol. 2019;6(9):e480–e488.
13. Russell NH, Wilhelm-Benartzi C, Othman J, et al. Fludarabine, Cytarabine, Granulocyte Colony-Stimulating Factor, and Idarubicin With Gemtuzumab Ozogamicin Improves Event-Free Survival in Younger Patients With Newly Diagnosed AML and Overall Survival in Patients With NPM1 and FLT3 Mutations . J Clin Oncol. 2024;42(10):1158-1168.
14. Martínez Sánchez MP, Megías-Vericat JE, Rodríguez-Veiga R, et al. A phase I trial of selinexor plus FLAG-Ida for the treatment of refractory/relapsed adult acute myeloid leukemia patients. Ann Hematol. 2021;100(6):1497–1508.
15. Saygin C, Larkin K, Blachly JS, Orwick S, Ngankeu A, Gregory CT, et al. A phase I study of lenalidomide plus chemotherapy with idarubicin and cytarabine in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome. Am J Hematol. 2020;95(12):1457–65.
16. Sweet K, Komrokji R, Padron E, et al. Phase I Clinical Trial of Selinexor in Combination with Daunorubicin and Cytarabine in Previously Untreated Poor-Risk Acute Myeloid Leukemia. Clin Cancer Res. 2020;26(1):54–60.
17. Wieduwilt MJ, Pawlowska N, Thomas S, et al. Histone deacetylase inhibition with panobinostat combined with intensive induction chemotherapy in older patients with acute myeloid leukemia: Phase I study results. Clin Cancer Res. 2019;25(16):4917–23.
18. Zeidner JF, Lee DJ, Frattini M, et al. Phase I study of alvocidib followed by 7+3 (cytarabine + daunorubicin) in newly diagnosed acute myeloid leukemia. Clin Cancer Res. 2021;27(1):60–69.
19. Zhang Y, Li X, Weng X, et al. Optimization of idarubicin and cytarabine induction regimen with homoharringtonine for newly diagnosed acute myeloid leukemia patients based on the peripheral blast clearance rate: A single-arm, phase 2 trial (RJ-AML 2014). Am J Hematol. 2022;97(1):43–51.
20. Abaza Y, McMahon C, Garcia JS. Advancements and Challenges in the Treatment of AML. Am Soc Clin Oncol Educ book. 2024;44(3):e438662.
21. Owattanapanich W, Owattanapanich N, Kungwankiattichai S, et al. Efficacy and Toxicity of Idarubicin Versus High-dose Daunorubicin for Induction Chemotherapy in Adult Acute Myeloid Leukemia: A Systematic Review and Meta-analysis. Clin Lymphoma Myeloma Leuk. 2018;18(12):814-821.e3.
22. Murphy T, Yee KWL. Cytarabine and daunorubicin for the treatment of acute myeloid leukemia. Expert Opin Pharmacother. 2017;18(16):1765–80.
23. Norsworthy KJ, Gao X, Ko CW, et al. Response Rate, Event-Free Survival, and Overall Survival in Newly Diagnosed Acute Myeloid Leukemia: US Food and Drug Administration Trial-Level and Patient-Level Analyses. J Clin Oncol. 2022;40(8):847–854.
24. Wang H, Xiao X, Xiao Q, et al. 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 (Baltimore). 2020;99(24):e20094.
25. Stubbins RJ, Francis A, Kuchenbauer F, et al. Management of Acute Myeloid Leukemia: A Review for General Practitioners in Oncology. Curr Oncol. 2022;29(9):6245–6259.
26. Rapoport BL, Herrstedt J, Snow RC, et al. 2023 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting. Support Care Cancer. 2023;32(1):36.
27. Sougiannis AT, VanderVeen BN, Davis JM, et al. Understanding chemotherapy-induced intestinal mucositis and strategies to improve gut resilience. Am J Physiol Gastrointest Liver Physiol. 2021;320(5):G712–G719.
28. Logan C, Koura D, Taplitz R. Updates in infection risk and management in acute leukemia. Hematology Am Soc Hematol Educ Program. 2020;2020(1):135-139.
29. Majid H, Masoom M, Bansal N, et al. Spectrum of infections in different regimens of post-induction chemotherapy in acute myeloid leukemia (de-novo): A comparative retrospective study. Heliyon. 2024;10(3):e24561.
30. Santoni A, Malchiodi M, Zappone E, et al. Infectious complications after induction chemotherapy with FLAI(E) in newly diagnosed AML, omitting antibacterial prophylaxis. Leukemia. 2023;37(7):1580–1582.
31. Buckley SA, Othus M, Vainstein V, et al. Prediction of adverse events during intensive induction chemotherapy for acute myeloid leukemia or high-grade myelodysplastic syndromes. Am J Hematol. 2014;89(4):423–8.
32. Zorawar S, Harmanpreet K. Cardiotoxicity induced by antineoplastic drug Daunorubicin and its amelioration: A review of literature. Blood Heart Circ. 2019;3(1):1–4.
33. Belay Y, Yirdaw K, Enawgaw B. Tumor Lysis Syndrome in Patients with Hematological Malignancies. J Oncol. 2017:2017:9684909.
34. Ballo O, Eladly F, Büttner S, et al. Acute kidney injury adversely affects the clinical course of acute myeloid leukemia patients undergoing induction chemotherapy. Ann Hematol. 2021;100(5):1159-1167.
35. Blair HA. Daunorubicin/Cytarabine Liposome: A Review in Acute Myeloid Leukaemia. Drugs. 2018;78(18):1903–1910.
2. Shimony S, Stahl M, Stone RM. Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023;98(3):502–26.
3. Jani CT, Ahmed A, Singh H, et al. Burden of AML, 1990-2019: Estimates From the Global Burden of Disease Study. JCO Glob Oncol. 2023;(9): e2300229.
4. Adige S, Lapidus RG, Carter-Cooper BA, et al. Equipotent doses of daunorubicin and idarubicin for AML: a meta-analysis of clinical trials versus in vitro estimation. Cancer Chemother Pharmacol. 2019;83(6):1105–12.
5. Cortes JE, Lin TL, Asubonteng K, et al. Efficacy and safety of CPX-351 versus 7 + 3 chemotherapy by European LeukemiaNet 2017 risk subgroups in older adults with newly diagnosed, high-risk/secondary AML: post hoc analysis of a randomized, phase 3 trial. J Hematol Oncol. 2022;15(1):155.
6. Ferrero D, Crisà E, Marmont F, et al. Survival improvement of poor-prognosis AML/MDS patients by maintenance treatment with low-dose chemotherapy and differentiating agents. Ann Hematol. 2014;93(8):1391–400.
7. Gill H, Yim R, Pang HH, et al. Clofarabine, cytarabine, and mitoxantrone in refractory/relapsed acute myeloid leukemia: High response rates and effective bridge to allogeneic hematopoietic stem cell transplantation. Cancer Med. 2020;9(10):3371–82.
8. Guolo F, Fianchi L, Minetto P, et al. CPX-351 treatment in secondary acute myeloblastic leukemia is effective and improves the feasibility of allogeneic stem cell transplantation: results of the Italian compassionate use program. Blood Cancer J. 2020;10(10):96.
9. Issa GC, Kantarjian HM, Xiao L, et al. Phase II trial of CPX-351 in patients with acute myeloid leukemia at high risk for induction mortality. Leukemia. 2020;34(11):2914–24.
10. Kadia TM, Reville PK, Borthakur G, et al. Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a cohort from a single-centre, single-arm, phase 2 trial. Lancet Haematol. 2021;8(8):e552–e561.
11. Muresan B, Mamolo C, Cappelleri JC, et al. Comparing cure rates for gemtuzumab ozogamicin plus standard chemotherapy vs standard chemotherapy alone in acute myeloid leukemia patients. Futur Oncol. 2021;17(22):2883–92.
12. Ravandi F, Assi R, Daver N, et al. Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a single-arm, phase 2 study. Lancet Haematol. 2019;6(9):e480–e488.
13. Russell NH, Wilhelm-Benartzi C, Othman J, et al. Fludarabine, Cytarabine, Granulocyte Colony-Stimulating Factor, and Idarubicin With Gemtuzumab Ozogamicin Improves Event-Free Survival in Younger Patients With Newly Diagnosed AML and Overall Survival in Patients With NPM1 and FLT3 Mutations . J Clin Oncol. 2024;42(10):1158-1168.
14. Martínez Sánchez MP, Megías-Vericat JE, Rodríguez-Veiga R, et al. A phase I trial of selinexor plus FLAG-Ida for the treatment of refractory/relapsed adult acute myeloid leukemia patients. Ann Hematol. 2021;100(6):1497–1508.
15. Saygin C, Larkin K, Blachly JS, Orwick S, Ngankeu A, Gregory CT, et al. A phase I study of lenalidomide plus chemotherapy with idarubicin and cytarabine in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome. Am J Hematol. 2020;95(12):1457–65.
16. Sweet K, Komrokji R, Padron E, et al. Phase I Clinical Trial of Selinexor in Combination with Daunorubicin and Cytarabine in Previously Untreated Poor-Risk Acute Myeloid Leukemia. Clin Cancer Res. 2020;26(1):54–60.
17. Wieduwilt MJ, Pawlowska N, Thomas S, et al. Histone deacetylase inhibition with panobinostat combined with intensive induction chemotherapy in older patients with acute myeloid leukemia: Phase I study results. Clin Cancer Res. 2019;25(16):4917–23.
18. Zeidner JF, Lee DJ, Frattini M, et al. Phase I study of alvocidib followed by 7+3 (cytarabine + daunorubicin) in newly diagnosed acute myeloid leukemia. Clin Cancer Res. 2021;27(1):60–69.
19. Zhang Y, Li X, Weng X, et al. Optimization of idarubicin and cytarabine induction regimen with homoharringtonine for newly diagnosed acute myeloid leukemia patients based on the peripheral blast clearance rate: A single-arm, phase 2 trial (RJ-AML 2014). Am J Hematol. 2022;97(1):43–51.
20. Abaza Y, McMahon C, Garcia JS. Advancements and Challenges in the Treatment of AML. Am Soc Clin Oncol Educ book. 2024;44(3):e438662.
21. Owattanapanich W, Owattanapanich N, Kungwankiattichai S, et al. Efficacy and Toxicity of Idarubicin Versus High-dose Daunorubicin for Induction Chemotherapy in Adult Acute Myeloid Leukemia: A Systematic Review and Meta-analysis. Clin Lymphoma Myeloma Leuk. 2018;18(12):814-821.e3.
22. Murphy T, Yee KWL. Cytarabine and daunorubicin for the treatment of acute myeloid leukemia. Expert Opin Pharmacother. 2017;18(16):1765–80.
23. Norsworthy KJ, Gao X, Ko CW, et al. Response Rate, Event-Free Survival, and Overall Survival in Newly Diagnosed Acute Myeloid Leukemia: US Food and Drug Administration Trial-Level and Patient-Level Analyses. J Clin Oncol. 2022;40(8):847–854.
24. Wang H, Xiao X, Xiao Q, et al. 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 (Baltimore). 2020;99(24):e20094.
25. Stubbins RJ, Francis A, Kuchenbauer F, et al. Management of Acute Myeloid Leukemia: A Review for General Practitioners in Oncology. Curr Oncol. 2022;29(9):6245–6259.
26. Rapoport BL, Herrstedt J, Snow RC, et al. 2023 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting. Support Care Cancer. 2023;32(1):36.
27. Sougiannis AT, VanderVeen BN, Davis JM, et al. Understanding chemotherapy-induced intestinal mucositis and strategies to improve gut resilience. Am J Physiol Gastrointest Liver Physiol. 2021;320(5):G712–G719.
28. Logan C, Koura D, Taplitz R. Updates in infection risk and management in acute leukemia. Hematology Am Soc Hematol Educ Program. 2020;2020(1):135-139.
29. Majid H, Masoom M, Bansal N, et al. Spectrum of infections in different regimens of post-induction chemotherapy in acute myeloid leukemia (de-novo): A comparative retrospective study. Heliyon. 2024;10(3):e24561.
30. Santoni A, Malchiodi M, Zappone E, et al. Infectious complications after induction chemotherapy with FLAI(E) in newly diagnosed AML, omitting antibacterial prophylaxis. Leukemia. 2023;37(7):1580–1582.
31. Buckley SA, Othus M, Vainstein V, et al. Prediction of adverse events during intensive induction chemotherapy for acute myeloid leukemia or high-grade myelodysplastic syndromes. Am J Hematol. 2014;89(4):423–8.
32. Zorawar S, Harmanpreet K. Cardiotoxicity induced by antineoplastic drug Daunorubicin and its amelioration: A review of literature. Blood Heart Circ. 2019;3(1):1–4.
33. Belay Y, Yirdaw K, Enawgaw B. Tumor Lysis Syndrome in Patients with Hematological Malignancies. J Oncol. 2017:2017:9684909.
34. Ballo O, Eladly F, Büttner S, et al. Acute kidney injury adversely affects the clinical course of acute myeloid leukemia patients undergoing induction chemotherapy. Ann Hematol. 2021;100(5):1159-1167.
35. Blair HA. Daunorubicin/Cytarabine Liposome: A Review in Acute Myeloid Leukaemia. Drugs. 2018;78(18):1903–1910.
| Files | ||
| Issue | Vol 19 No 3 (2025) | |
| Section | Review Article(s) | |
| Keywords | ||
| Acute myeloid leukemia (AML); Efficacy; Induction chemotherapy, Prognosis | ||
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How to Cite
1.
Komara IMAN, Suega K, Rena NMRA, Adnyana IWL. Evaluation of Efficacy, Safety, and Prognostic Value of Induction Chemotherapy in Patients with Acute Myeloid Leukemia: An Updated Meta-Analysis of a 5-Year Study. Int J Hematol Oncol Stem Cell Res. 2025;19(3):248-260.
