Acute Myeloid Leukemia (AML) Questions & Answers

1. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19. 127 (20):2391-405. [QxMD MEDLINE Link]. [Full Text].

2. Smith MT, Skibola CF, Allan JM, Morgan GJ. Causal models of leukaemia and lymphoma. IARC Sci Publ. 2004. 373-92. [QxMD MEDLINE Link].

3. Ghiaur G, Wroblewski M, Loges S. Acute Myelogenous Leukemia and its Microenvironment: A Molecular Conversation. Semin Hematol. 2015 Jul. 52 (3):200-6. [QxMD MEDLINE Link].

4. Larson RA, Wang Y, Banerjee M, Wiemels J, Hartford C, Le Beau MM, et al. Prevalence of the inactivating 609C-->T polymorphism in the NAD(P)H:quinone oxidoreductase (NQO1) gene in patients with primary and therapy-related myeloid leukemia. Blood. 1999 Jul 15. 94(2):803-7. [QxMD MEDLINE Link]. [Full Text].

5. Allan JM, Wild CP, Rollinson S, Willett EV, Moorman AV, Dovey GJ, et al. Polymorphism in glutathione S-transferase P1 is associated with susceptibility to chemotherapy-induced leukemia. Proc Natl Acad Sci U S A. 2001 Sep 25. 98(20):11592-7. [QxMD MEDLINE Link]. [Full Text].

6. Song WJ, Sullivan MG, Legare RD, Hutchings S, Tan X, Kufrin D, et al. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet. 1999 Oct. 23(2):166-75. [QxMD MEDLINE Link].

7. Smith ML, Cavenagh JD, Lister TA, Fitzgibbon J. Mutation of CEBPA in familial acute myeloid leukemia. N Engl J Med. 2004 Dec 2. 351(23):2403-7. [QxMD MEDLINE Link]. [Full Text].

8. Holme H, Hossain U, Kirwan M, Walne A, Vulliamy T, Dokal I. Marked genetic heterogeneity in familial myelodysplasia/acute myeloid leukaemia. Br J Haematol. 2012 Jul. 158(2):242-8. [QxMD MEDLINE Link].

9. Gao J, Gentzler RD, Timms AE, Horwitz MS, Frankfurt O, Altman JK. Heritable GATA2 mutations associated with familial AML-MDS: a case report and review of literature. J Hematol Oncol. 2014 Apr 22. 7(1):36. [QxMD MEDLINE Link].

10. Guidugli L, Johnson AK, Alkorta-Aranburu G, Nelakuditi V, Arndt K, Churpek JE, et al. Clinical utility of gene panel-based testing for hereditary myelodysplastic syndrome/acute leukemia predisposition syndromes. Leukemia. 2017 May. 31 (5):1226-1229. [QxMD MEDLINE Link].

11. Brownson RC, Chang JC, Davis JR. Cigarette smoking and risk of adult leukemia. Am J Epidemiol. 1991 Nov 1. 134(9):938-41. [QxMD MEDLINE Link].

12. Poynter JN, Richardson M, Roesler M, Blair CK, Hirsch B, Nguyen P, et al. Chemical exposures and risk of acute myeloid leukemia and myelodysplastic syndromes in a population-based study. Int J Cancer. 2016 Sep 7. [QxMD MEDLINE Link].

13. Smith RE, Bryant J, DeCillis A, Anderson S. Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the National Surgical Adjuvant Breast and Bowel Project Experience. J Clin Oncol. 2003 Apr 1. 21(7):1195-204. [QxMD MEDLINE Link]. [Full Text].

14. Andersen MK, Larson RA, Mauritzson N, Schnittger S, Jhanwar SC, Pedersen-Bjergaard J. Balanced chromosome abnormalities inv(16) and t(15;17) in therapy-related myelodysplastic syndromes and acute leukemia: report from an international workshop. Genes Chromosomes Cancer. 2002 Apr. 33(4):395-400. [QxMD MEDLINE Link].

15. Cancer Facts & Figures 2023. American Cancer Society. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2023/2023-cancer-facts-and-figures.pdf. Accessed: April 27, 2023.

16. Valk PJ, Verhaak RG, Beijen MA, Erpelinck CA, Barjesteh van Waalwijk van Doorn-Khosrovani S, Boer JM, et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med. 2004 Apr 15. 350(16):1617-28. [QxMD MEDLINE Link]. [Full Text].

17. Taskesen E, Bullinger L, Corbacioglu A, Sanders MA, Erpelinck CA, Wouters BJ, et al. Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPA double mutant AML as a distinctive disease entity. Blood. 2011 Feb 24. 117(8):2469-75. [QxMD MEDLINE Link].

18. Taylor J, Xiao W, Abdel-Wahab O. Diagnosis and classification of hematologic malignancies on the basis of genetics. Blood. 2017 Jul 27. 130 (4):410-423. [QxMD MEDLINE Link].

19. Metzeler KH, Maharry K, Radmacher MD, et al. TET2 Mutations Improve the New European LeukemiaNet Risk Classification of Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study. J Clin Oncol. 2011 Apr 1. 29(10):1373-81. [QxMD MEDLINE Link].

20. Bower H, Andersson TM, Björkholm M, Dickman PW, Lambert PC, Derolf ÅR. Continued improvement in survival of acute myeloid leukemia patients: an application of the loss in expectation of life. Blood Cancer J. 2016 Feb 5. 6:e390. [QxMD MEDLINE Link].

21. McNerney ME, Godley LA, Le Beau MM. Therapy-related myeloid neoplasms: when genetics and environment collide. Nat Rev Cancer. 2017 Aug 24. 17 (9):513-527. [QxMD MEDLINE Link].

22. Kayser S, Dohner K, Krauter J, et al. The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Blood. 2011 Feb 17. 117(7):2137-45. [QxMD MEDLINE Link].

23. Varadarajan R, Licht AS, Hyland AJ, et al. Smoking adversely affects survival in acute myeloid leukemia patients. Int J Cancer. 2012 Mar 15. 130(6):1451-8. [QxMD MEDLINE Link]. [Full Text].

24. Crysandt M, Kramer M, Ehninger G, Bornhäuser M, Berdel WE, et al. A high BMI is a risk factor in younger patients with de novo acute myelogenous leukemia. Eur J Haematol. 2015 Aug 16. [QxMD MEDLINE Link].

25. [Guideline] NCCN Clinical Practice Guidelines in Oncology. Acute Myeloid Leukemia. National Comprehensive Cancer Network. Available at https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Version 3.2023 — April 5, 2023; Accessed: April 27, 2023.

26. [Guideline] Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017 Jan 26. 129 (4):424-447. [QxMD MEDLINE Link]. [Full Text].

27. Breems DA, Van Putten WL, De Greef GE, Van Zelderen-Bhola SL, Gerssen-Schoorl KB, Mellink CH, et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol. 2008 Oct 10. 26(29):4791-7. [QxMD MEDLINE Link].

28. Voutiadou G, Papaioannou G, Gaitatzi M, Lalayanni C, Syrigou A, Vadikoliou C, et al. Monosomal karyotype in acute myeloid leukemia defines a distinct subgroup within the adverse cytogenetic risk category. Cancer Genet. 2013 Jan-Feb. 206(1-2):32-6. [QxMD MEDLINE Link].

29. Haferlach C, Alpermann T, Schnittger S, Kern W, Chromik J, Schmid C, et al. Prognostic value of monosomal karyotype in comparison to complex aberrant karyotype in acute myeloid leukemia: a study on 824 cases with aberrant karyotype. Blood. 2012 Mar 1. 119(9):2122-5. [QxMD MEDLINE Link].

30. Griswold IJ, Shen LJ, La Rosée P, Demehri S, Heinrich MC, Braziel RM, et al. Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis. Blood. 2004 Nov 1. 104(9):2912-8. [QxMD MEDLINE Link]. [Full Text].

31. Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005 Jan 20. 352(3):254-66. [QxMD MEDLINE Link]. [Full Text].

32. Thiede C, Steudel C, Mohr B, Schaich M, Schäkel U, Platzbecker U, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood. 2002 Jun 15. 99(12):4326-35. [QxMD MEDLINE Link]. [Full Text].

33. Fröhling S, Schlenk RF, Stolze I, Bihlmayr J, Benner A, Kreitmeier S, et al. CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations. J Clin Oncol. 2004 Feb 15. 22(4):624-33. [QxMD MEDLINE Link]. [Full Text].

34. Schwind S, Marcucci G, Maharry K, Radmacher MD, Mrózek K, Holland KB, et al. BAALC and ERG expression levels are associated with outcome and distinct gene and microRNA expression profiles in older patients with de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood. 2010 Dec 16. 116(25):5660-9. [QxMD MEDLINE Link]. [Full Text].

35. Ley TJ, Ding L, Walter MJ, McLellan MD, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med. 2010 Dec 16. 363(25):2424-33. [QxMD MEDLINE Link].

36. Schwind S, Maharry K, Radmacher MD, Mrózek K, Holland KB, Margeson D, et al. Prognostic significance of expression of a single microRNA, miR-181a, in cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol. 2010 Dec 20. 28(36):5257-64. [QxMD MEDLINE Link]. [Full Text].

37. Conway O'Brien E, Prideaux S, Chevassut T. The epigenetic landscape of acute myeloid leukemia. Adv Hematol. 2014. 2014:103175. [QxMD MEDLINE Link]. [Full Text].

38. Marcucci G, Yan P, Maharry K, Frankhouser D, Nicolet D, Metzeler KH, et al. Epigenetics meets genetics in acute myeloid leukemia: clinical impact of a novel seven-gene score. J Clin Oncol. 2014 Feb 20. 32(6):548-56. [QxMD MEDLINE Link]. [Full Text].

39. Marcucci G, Maharry K, Wu YZ, Radmacher MD, Mrózek K, Margeson D, et al. IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol. 2010 May 10. 28(14):2348-55. [QxMD MEDLINE Link]. [Full Text].

40. Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022 Sep 15. 140 (11):1200-1228. [QxMD MEDLINE Link]. [Full Text].

41. Schechter T, Gassas A, Chen H, Pollard J, Meshinchi S, Zaidman I, et al. The outcome of allogeneic hematopoietic cell transplantation for children with FMS-like tyrosine kinase 3 internal tandem duplication-positive acute myelogenous leukemia. Biol Blood Marrow Transplant. 2015 Jan. 21 (1):172-5. [QxMD MEDLINE Link].

42. DiNardo CD, Cortes JE. New treatment for acute myelogenous leukemia. Expert Opin Pharmacother. 2015 Jan. 16 (1):95-106. [QxMD MEDLINE Link].

43. Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009 Sep 24. 361(13):1249-59. [QxMD MEDLINE Link].

44. Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24. 361(13):1235-48. [QxMD MEDLINE Link].

45. Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, et al. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18. 125 (25):3878-85. [QxMD MEDLINE Link].

46. Liu H, Fu R, Li L, Wang G, Song J, Ruan E, et al. Comparison of Reduced-Intensity Idarubicin and Daunorubicin Plus Cytarabine as Induction Chemotherapy for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia. Clin Drug Investig. 2017 Feb. 37 (2):167-174. [QxMD MEDLINE Link].

47. Lowenberg B, Pabst T, Vellenga E, et al. Cytarabine dose for acute myeloid leukemia. N Engl J Med. 2011 Mar 17. 364(11):1027-36. [QxMD MEDLINE Link].

48. Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, et al. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation. N Engl J Med. 2017 Aug 3. 377 (5):454-464. [QxMD MEDLINE Link].

49. Wierzbowska A, Robak T, Pluta A, et al. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb. 80(2):115-26. [QxMD MEDLINE Link].

50. Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, et al. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10. 30 (20):2441-8. [QxMD MEDLINE Link].

51. Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med. 1994 Oct 6. 331(14):896-903. [QxMD MEDLINE Link]. [Full Text].

52. Li R, Hu X, Wang L, Cheng H, Lv S, Zhang W, et al. Fludarabine and Cytarabine versus High-dose Cytarabine in Consolidation Treatment of t(8; 21) Acute Myeloid Leukemia: a prospective, randomized study. Am J Hematol. 2016 Sep 27. [QxMD MEDLINE Link].

53. Jen EY, Wang X, Li M, Li H, Lee SL, Ni N, et al. FDA Approval Summary: Oral Azacitidine for Continued Treatment of Adults with Acute Myeloid Leukemia Unable to Complete Intensive Curative Therapy. Clin Cancer Res. 2022 Jul 15. 28 (14):2989-2993. [QxMD MEDLINE Link]. [Full Text].

54. [Guideline] Majhail NS, Farnia SH, Carpenter PA, Champlin RE, Crawford S, Marks DI, et al. Indications for Autologous and Allogeneic Hematopoietic Cell Transplantation: Guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015 Nov. 21 (11):1863-1869. [QxMD MEDLINE Link]. [Full Text].

55. FDA approves Mylotarg for treatment of acute myeloid leukemia. Medscape Medical News. Available at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574507.htm. September 1, 2017; Accessed: May 26, 2020.

56. Castaigne S, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21. 379 (9825):1508-16. [QxMD MEDLINE Link]. [Full Text].

57. Amadori S, et al. Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial. J Clin Oncol. 2016 Mar 20. 34 (9):972-9. [QxMD MEDLINE Link]. [Full Text].

58. Menzin J, Lang K, Earle CC, Kerney D, Mallick R. The outcomes and costs of acute myeloid leukemia among the elderly. Arch Intern Med. 2002 Jul 22. 162(14):1597-603. [QxMD MEDLINE Link]. [Full Text].

59. Löwenberg B, Zittoun R, Kerkhofs H, Jehn U, Abels J, Debusscher L, et al. On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol. 1989 Sep. 7(9):1268-74. [QxMD MEDLINE Link].

60. Kantarjian H, O'brien S, Cortes J, Giles F, Faderl S, Jabbour E, et al. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer. 2006 Mar 1. 106(5):1090-8. [QxMD MEDLINE Link]. [Full Text].

61. Lancet JE, Uy GL, Cortes JE, Newell LF, Lin RL, Ritchie EK, et al. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. Journal of Clinical Oncology. May 2016. 34(15):7000. [Full Text].

62. Cortes JE, et al. A phase 2 randomized study of low dose Ara-C with or without glasdegib (PF-04449913) in untreated patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. Blood 2016;128:99. [Full Text].

63. Zeidan AM, Schuster MW, Krauter J, et al. Clinical Benefit of Glasdegib in Combination with Azacitidine or Low-Dose Cytarabine in Patients with Acute Myeloid Leukemia. Blood. 2019. 134 (Supplement 1):3916. [Full Text].

64. Pollyea DA, et al. Venetoclax in combination with hypomethylating agents induces rapid, deep, and durable responses in patients with AML ineligible for intensive therapy. Blood 2018;132:285. [Full Text].

65. Wei A, et al. Venetoclax with low-dose cytarabine induces rapid, deep, and durable responses in previously untreated older adults with AML ineligible for intensive chemotherapy. Blood 2018;132:284. [Full Text].

66. FDA Grants Venetoclax Combination Full Approval for Newly Diagnosed AML. ASH Clinical News. Available at https://www.ashclinicalnews.org/online-exclusives/fda-grants-venetoclax-combination-full-approval-newly-diagnosed-aml/. October 25, 2020; Accessed: October 26, 2020.

67. Welch JS, Petti AA, Miller CA, Fronick CC, O'Laughlin M, Fulton RS, et al. TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes. N Engl J Med. 2016 Nov 24. 375 (21):2023-2036. [QxMD MEDLINE Link].

68. Thépot S, Itzykson R, Seegers V, Recher C, Raffoux E, et al. Azacitidine in untreated acute myeloid leukemia: a report on 149 patients. Am J Hematol. 2014 Apr. 89 (4):410-6. [QxMD MEDLINE Link].

69. Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16. 126 (3):291-9. [QxMD MEDLINE Link]. [Full Text].

70. Itzykson R, Thépot S, Berthon C, Delaunay J, Bouscary D, Cluzeau T, et al. Azacitidine for the treatment of relapsed and refractory AML in older patients. Leuk Res. 2015 Feb. 39 (2):124-30. [QxMD MEDLINE Link].

71. He PF, Zhou JD, Yao DM, Ma JC, Wen XM, Zhang ZH, et al. Efficacy and safety of decitabine in treatment of elderly patients with acute myeloid leukemia: A systematic review and meta-analysis. Oncotarget. 2017 Jun 20. 8 (25):41498-41507. [QxMD MEDLINE Link]. [Full Text].

72. Bian MR, Yang HS, Lin GQ, Wan Y, Wang L, Si YJ, et al. Decitabine Compared With Conventional Regimens in Older Patients With Acute Myeloid Leukemia: A Meta-Analysis. Clin Lymphoma Myeloma Leuk. 2019 Dec. 19 (12):e636-e648. [QxMD MEDLINE Link]. [Full Text].

73. Talati C, Dhulipala VC, Extermann MT, Ali NA, Kim J, Komrokji R, et al. Comparisons of commonly used front-line regimens on survival outcomes in patients aged 70 years and older with acute myeloid leukemia. Haematologica. 2020. 105 (2):398-406. [QxMD MEDLINE Link]. [Full Text].

74. Tibsovo (ivosidenib) [package insert]. Cambridge, MA: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211192s001lbl.pdf. May 2019. Available at [Full Text].

75. FDA approves ivosidenib in combination with azacitidine for newly diagnosed acute myeloid leukemia. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ivosidenib-combination-azacitidine-newly-diagnosed-acute-myeloid-leukemia. May 25, 2022; Accessed: May 26, 2022.

76. Burnett AK, Milligan D, Prentice AG, Goldstone AH, McMullin MF, Hills RK, et al. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer. 2007 Mar 15. 109(6):1114-24. [QxMD MEDLINE Link]. [Full Text].

77. Burnett AK, Milligan D, Prentice AG, et al. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer. 2007 Mar 15. 109(6):1114-24. [QxMD MEDLINE Link].

78. Faderl S, Verstovsek S, Cortes J, Ravandi F, Beran M, Garcia-Manero G, et al. Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients 50 years of age or older. Blood. 2006 Jul 1. 108(1):45-51. [QxMD MEDLINE Link]. [Full Text].

79. Pingali SR, Champlin RE. Pushing the envelope-nonmyeloablative and reduced intensity preparative regimens for allogeneic hematopoietic transplantation. Bone Marrow Transplant. 2015 Sep. 50 (9):1157-67. [QxMD MEDLINE Link]. [Full Text].

80. de Lima M, Anagnostopoulos A, Munsell M, Shahjahan M, Ueno N, Ippoliti C, et al. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood. 2004 Aug 1. 104(3):865-72. [QxMD MEDLINE Link]. [Full Text].

81. Slavin S, Nagler A, Shapira MY, Aker M, Gabriel C, Or R. Treatment of leukemia by alloreactive lymphocytes and nonmyeloablative stem cell transplantation. J Clin Immunol. 2002 Mar. 22(2):64-9. [QxMD MEDLINE Link].

82. Storb RF, Champlin R, Riddell SR, Murata M, Bryant S, Warren EH. Non-myeloablative transplants for malignant disease. Hematology Am Soc Hematol Educ Program. 2001. 375-91. [QxMD MEDLINE Link]. [Full Text].

83. Sengsayadeth S, Savani BN, Blaise D, Malard F, Nagler A, Mohty M. Reduced intensity conditioning allogeneic hematopoietic cell transplantation for adult acute myeloid leukemia in complete remission - a review from the Acute Leukemia Working Party of the EBMT. Haematologica. 2015 Jul. 100 (7):859-69. [QxMD MEDLINE Link]. [Full Text].

84. Farag SS, et al; Acute Leukemia Committee of the Center for International Blood and Marrow Transplant Research and Cancer and Leukemia Group B. Comparison of reduced-intensity hematopoietic cell transplantation with chemotherapy in patients age 60-70 years with acute myelogenous leukemia in first remission. Biol Blood Marrow Transplant. 2011 Dec. 17 (12):1796-803. [QxMD MEDLINE Link]. [Full Text].

85. Bhatia S. Therapy-related myelodysplasia and acute myeloid leukemia. Semin Oncol. 2013 Dec. 40 (6):666-75. [QxMD MEDLINE Link]. [Full Text].

86. Erba H, Stone RM. Teaching Old Drugs New Tricks?. ASH Clinical News. Available at https://www.ashclinicalnews.org/features/teaching-old-drugs-new-tricks/. March 1, 2018; Accessed: November 29. 2018.

87. Chen ZX, Xue YQ, Zhang R, Tao RF, Xia XM, Li C, et al. A clinical and experimental study on all-trans retinoic acid-treated acute promyelocytic leukemia patients. Blood. 1991 Sep 15. 78(6):1413-9. [QxMD MEDLINE Link]. [Full Text].

88. Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, et al. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1999 Aug 15. 94(4):1192-200. [QxMD MEDLINE Link]. [Full Text].

89. de Botton S, Fawaz A, Chevret S, Dombret H, Thomas X, Sanz M, et al. Autologous and allogeneic stem-cell transplantation as salvage treatment of acute promyelocytic leukemia initially treated with all-trans-retinoic acid: a retrospective analysis of the European acute promyelocytic leukemia group. J Clin Oncol. 2005 Jan 1. 23(1):120-6. [QxMD MEDLINE Link]. [Full Text].

90. Frankel SR, Eardley A, Lauwers G, Weiss M, Warrell RP Jr. The "retinoic acid syndrome" in acute promyelocytic leukemia. Ann Intern Med. 1992 Aug 15. 117(4):292-6. [QxMD MEDLINE Link].

91. Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. 1997 Oct 9. 337 (15):1021-8. [QxMD MEDLINE Link].

92. Adès L, Guerci A, Raffoux E, Sanz M, Chevallier P, Lapusan S, et al. Very long-term outcome of acute promyelocytic leukemia after treatment with all-trans retinoic acid and chemotherapy: the European APL Group experience. Blood. 2010 Mar 4. 115 (9):1690-6. [QxMD MEDLINE Link].

93. Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, et al. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20. 24(36):5703-10. [QxMD MEDLINE Link]. [Full Text].

94. Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, et al. In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood. 1996 Aug 1. 88 (3):1052-61. [QxMD MEDLINE Link].

95. Chen GQ, Shi XG, Tang W, Xiong SM, Zhu J, Cai X, et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): I. As2O3 exerts dose-dependent dual effects on APL cells. Blood. 1997 May 1. 89 (9):3345-53. [QxMD MEDLINE Link].

96. Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood. 1997 May 1. 89 (9):3354-60. [QxMD MEDLINE Link].

97. Powell BL, Moser B, Stock W, et al. Effect of consolidation with arsenic trioxide (As2O3) on event-free survival (EFS) and overall survival (OS) among patients with newly diagnosed acute promyelocytic leukemia (APL): North American Intergroup Protocol C9710. J Clin Oncol. 2007. 25 (18S June 20 supp):2.

98. Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11. 369(2):111-21. [QxMD MEDLINE Link].

99. Estey E, Kornblau S, Pierce S, Kantarjian H, Beran M, Keating M. A stratification system for evaluating and selecting therapies in patients with relapsed or primary refractory acute myelogenous leukemia. Blood. 1996 Jul 15. 88(2):756. [QxMD MEDLINE Link]. [Full Text].

100. Giles F, O'Brien S, Cortes J, et al. Outcome of patients with acute myelogenous leukemia after second salvage therapy. Cancer. 2005 Aug 1. 104(3):547-54. [QxMD MEDLINE Link].

101. Amadori S, Arcese W, Isacchi G, et al. Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia. J Clin Oncol. 1991 Jul. 9(7):1210-4. [QxMD MEDLINE Link].

102. Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med. 2019 Oct 31. 381 (18):1728-1740. [QxMD MEDLINE Link]. [Full Text].

103. DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, et al. Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. N Engl J Med. 2018 Jun 21. 378 (25):2386-2398. [QxMD MEDLINE Link]. [Full Text].

104. Norsworthy KJ, Luo L, Hsu V, Gudi R, Dorff SE, Przepiorka D, et al. FDA Approval Summary: Ivosidenib for Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase-1 Mutation. Clin Cancer Res. 2019 Jun 1. 25 (11):3205-3209. [QxMD MEDLINE Link].

105. Open-label study of FT-2102 with or without azacitidine or cytarabine in patients with AML or MDS with an IDH1 mutation. ClinicalTrials.gov. Available at https://clinicaltrials.gov/ct2/show/NCT02719574. March 3, 2022; Accessed: December 5, 2022.

106. Lamba JK, Chauhan L, Shin M, Loken MR, Pollard JA, Wang YC, et al. CD33 Splicing Polymorphism Determines Gemtuzumab Ozogamicin Response in De Novo Acute Myeloid Leukemia: Report From Randomized Phase III Children's Oncology Group Trial AAML0531. J Clin Oncol. 2017 Aug 10. 35 (23):2674-2682. [QxMD MEDLINE Link].

107. Mardiana S, Gill S. CAR T Cells for Acute Myeloid Leukemia: State of the Art and Future Directions. Front Oncol. 2020. 10:697. [QxMD MEDLINE Link]. [Full Text].

108. Issa GC, Aldoss I, DiPersio J, et al. The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. Nature. 2023 Mar. 615 (7954):920-924. [QxMD MEDLINE Link]. [Full Text].

109. Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007 Jan 25. 356(4):348-59. [QxMD MEDLINE Link]. [Full Text].

110. Ohno R, Tomonaga M, Kobayashi T, Kanamaru A, Shirakawa S, Masaoka T, et al. Effect of granulocyte colony-stimulating factor after intensive induction therapy in relapsed or refractory acute leukemia. N Engl J Med. 1990 Sep 27. 323(13):871-7. [QxMD MEDLINE Link].

111. Dombret H, Chastang C, Fenaux P, Reiffers J, Bordessoule D, Bouabdallah R, et al. A controlled study of recombinant human granulocyte colony-stimulating factor in elderly patients after treatment for acute myelogenous leukemia. AML Cooperative Study Group. N Engl J Med. 1995 Jun 22. 332(25):1678-83. [QxMD MEDLINE Link]. [Full Text].

112. Godwin JE, Kopecky KJ, Head DR, Willman CL, Leith CP, Hynes HE, et al. A double-blind placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: a Southwest oncology group study (9031). Blood. 1998 May 15. 91(10):3607-15. [QxMD MEDLINE Link]. [Full Text].

113. Rowe JM, Andersen JW, Mazza JJ, Bennett JM, Paietta E, Hayes FA, et al. A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (> 55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood. 1995 Jul 15. 86(2):457-62. [QxMD MEDLINE Link]. [Full Text].

114. Stone RM, Berg DT, George SL, Dodge RK, Paciucci PA, Schulman P, et al. Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. Cancer and Leukemia Group B. N Engl J Med. 1995 Jun 22. 332(25):1671-7. [QxMD MEDLINE Link]. [Full Text].

115. Zittoun R, Suciu S, Mandelli F, de Witte T, Thaler J, Stryckmans P, et al. Granulocyte-macrophage colony-stimulating factor associated with induction treatment of acute myelogenous leukemia: a randomized trial by the European Organization for Research and Treatment of Cancer Leukemia Cooperative Group. J Clin Oncol. 1996 Jul. 14(7):2150-9. [QxMD MEDLINE Link].

116. [Guideline] Arber DA, Borowitz MJ, Cessna M, Etzell J, Foucar K, Hasserjian RP, et al. Initial Diagnostic Workup of Acute Leukemia: Guideline From the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med. 2017 Feb 22. [QxMD MEDLINE Link]. [Full Text].

117. [Guideline] Heuser M, Ofran Y, Boissel N, Brunet Mauri S, Craddock C, Janssen J, et al. Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Mar 17. 24 Suppl 6:vi138-43. [QxMD MEDLINE Link]. [Full Text].

118. [Guideline] Sekeres MA, Guyatt G, Abel G, et al. American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults. Blood Adv. 2020 Aug 11. 4 (15):3528-3549. [QxMD MEDLINE Link]. [Full Text].

119. Erba HP, Montesinos P, Kim HJ, et al. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 May 13. 401 (10388):1571-1583. [QxMD MEDLINE Link]. [Full Text].

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MD, FRCPC, DTM&H Professor Emeritus of Internal Medicine and Hematology/Oncology, Emeritus Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MD, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Clarence Sarkodee Adoo, MD, FACP Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program

Clarence Sarkodee Adoo, MD, FACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

• Print this section
• Print the entire contents of
• Print the entire contents of article