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Treatment of Elderly Acute Myeloid Leukemia Patients

  • Leukemia (Janice Dutcher, section editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Older patients with acute myelogenous leukemia (AML) fare much less well than younger patients with the same disease due to a combination of comorbidities and intrinsic disease resistance. Likely due to aging of the US population, the median age of AML patients at diagnosis has increased from 68 to 72 years. AML is a heterogeneous disease, particularly in older patients, making therapeutic decisions challenging. Older patients who are ‘fit’ for intensive chemotherapy and would have a reasonable chance to benefit based on host and disease characteristics should receive standard induction chemotherapy with 7 days of continuous infusion of cytarabine and at least 60 mg/m2 daunorubicin daily for 3 days. Therapeutic options for patients who are not candidates for or are not likely to respond to intensive therapy include clofarabine, low intensity chemotherapy such as low dose cytarabine, hypomethylating agents, or investigational agents. For older AML patients in complete remission, post-remission or consolidation chemotherapy with repeat induction or modified high dose cytarabine may offer a small chance for long term disease-free survival. Selected older patients who achieve remission by any means should be considered for reduced-intensity stem cell transplantation which may offer improved chances of cure and survival compared with standard post-remission chemotherapy.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Juliusson G, Antunovic P, Derolf A, et al. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood 2009;113:4179–87.

    Article  PubMed  CAS  Google Scholar 

  2. Rowe JM, Tallman MS. How I treat acute myeloid leukemia. Blood. 2010;116:3147–56. This article is a comprehensive review of approaches to AML treatment in various clinical scenarios.

    Google Scholar 

  3. Stone RM, O’Donnell MR, Sekeres MA. Acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2004;98–117.

  4. Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood. 2006;107:3481–5.

    Article  PubMed  CAS  Google Scholar 

  5. Klepin HD, Balducci L. Acute myelogenous leukemia in older adults. Oncologist. 2009;14:222–32.

    Article  PubMed  CAS  Google Scholar 

  6. Alibhai SM, Leach M, Minden MD, et al. Outcomes and quality of care in acute myeloid leukemia over 40 years. Cancer. 2009;115:2903–11.

    Article  PubMed  Google Scholar 

  7. Lang K, Earle CC, Foster T, et al. Trends in the treatment of acute myeloid leukaemia in the elderly. Drugs Aging. 2005;22:943–55.

    Article  PubMed  Google Scholar 

  8. Grimwade D, Walker H, Harrison G, et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98:1312–20.

    Article  PubMed  CAS  Google Scholar 

  9. Medeiros BC, Othus M, Fang M, et al. Prognostic impact of monosomal karyotype in young adult and elderly acute myeloid leukemia: the Southwest Oncology Group (SWOG) experience. Blood. 2010;116:2224–8.

    Article  PubMed  CAS  Google Scholar 

  10. Motyckova G, Stone RM. The role of molecular tests in acute myelogenous leukemia treatment decisions. Curr Hematol Malig Rep. 2010;5:109–17.

    Article  PubMed  Google Scholar 

  11. Schlenk RF, Dohner K. Impact of new prognostic markers in treatment decisions in acute myeloid leukemia. Curr Opin Hematol. 2009;16:98–104.

    Article  PubMed  CAS  Google Scholar 

  12. Buchner T, Berdel WE, Haferlach C, et al. Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: a study by the German Acute Myeloid Leukemia Cooperative Group. J Clin Oncol. 2009;27:61–9.

    Article  PubMed  Google Scholar 

  13. Schlenk RF, Dohner K, Krauter J, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358:1909–18.

    Article  PubMed  CAS  Google Scholar 

  14. Whitman SP, Maharry K, Radmacher MD, et al. FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood 2010;116:3622–6.

    Article  PubMed  CAS  Google Scholar 

  15. Falini B, Martelli MP, Bolli N, et al. Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity? Blood. 2011;117:1109–20.

  16. Becker H, Marcucci G, Maharry K, et al. Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study. J Clin Oncol. 2010;28:596–604.

    Article  PubMed  CAS  Google Scholar 

  17. Paschka P, Schlenk RF, Gaidzik VI, et al. IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication. J Clin Oncol. 2010;28:3636–43.

    Article  PubMed  CAS  Google Scholar 

  18. Marcucci G, Maharry K, Wu YZ, 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;28:2348–55.

    Article  PubMed  CAS  Google Scholar 

  19. Schwind S, Marcucci G, Maharry K, 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;116:5660–9.

    Article  PubMed  CAS  Google Scholar 

  20. Frohling S, Schlenk RF, Kayser S, et al. Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B. Blood. 2006;108:3280–8.

    Article  PubMed  CAS  Google Scholar 

  21. Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010;116:354–65.

    Article  PubMed  CAS  Google Scholar 

  22. Farag SS, Archer KJ, Mrozek K, et al. Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461. Blood. 2006;108:63–73.

    Article  PubMed  CAS  Google Scholar 

  23. Wheatley K, Brookes CL, Howman AJ, et al. Prognostic factor analysis of the survival of elderly patients with AML in the MRC AML11 and LRF AML14 trials. Br J Haematol. 2009;145:598–605.

    Article  PubMed  Google Scholar 

  24. Kantarjian H, Ravandi F, O’Brien S, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood. 2010;116:4422-9. The article analyzed factors important in therapy responsiveness and survival in older AML patients undergoing induction chemotherapy and found that an increased 8 week mortality was associated with age over 80 together with complex karyotype, poor performance status (ECOG 2–4) and elevated creatinine.

    Google Scholar 

  25. Lowenberg B, Zittoun R, Kerkhofs H, 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;7:1268–74.

    PubMed  CAS  Google Scholar 

  26. Tilly H, Castaigne S, Bordessoule D, et al. Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly. J Clin Oncol. 1990;8:272–9.

    PubMed  CAS  Google Scholar 

  27. Lowenberg B, Ossenkoppele GJ, van Putten W, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009;361:1235–48.

    Article  PubMed  Google Scholar 

  28. Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia.[see comment]. N Engl J Med. 2009;361:1249–59.

    Article  PubMed  CAS  Google Scholar 

  29. Walter RB, Kantarjian HM, Huang X, et al. Effect of complete remission and responses less than complete remission on survival in acute myeloid leukemia: a combined Eastern Cooperative Oncology Group, Southwest Oncology Group, and M. D. Anderson Cancer Center Study. J Clin Oncol. 2010;28:1766–71.

    Article  PubMed  Google Scholar 

  30. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10:223–32.

    Article  PubMed  CAS  Google Scholar 

  31. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010;28:562–9.

    Article  PubMed  CAS  Google Scholar 

  32. Cashen AF, Schiller GJ, O’Donnell MR, et al. Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol. 2010;28:556–61.

    Article  PubMed  CAS  Google Scholar 

  33. Blum W, Klisovic RB, Hackanson B, et al. Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. J Clin Oncol. 2007;25:3884–91.

    Article  PubMed  CAS  Google Scholar 

  34. Levi JA, Wiernik PH. A comparative clinical trial of 5-azacytidine and guanazole in previously treated adults with acute nonlymphocytic leukemia. Cancer. 1976;38:36–41.

    Article  PubMed  CAS  Google Scholar 

  35. Vogler WR, Miller DS, Keller JW. 5-Azacytidine (NSC 102816): a new drug for the treatment of myeloblastic leukemia. Blood. 1976;48:331–7.

    PubMed  CAS  Google Scholar 

  36. 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;109:1114–24.

    Article  PubMed  CAS  Google Scholar 

  37. Kantarjian HM, Erba HP, Claxton D, et al. Phase II study of clofarabine monotherapy in previously untreated older adults with acute myeloid leukemia and unfavorable prognostic factors. J Clin Oncol. 2010;28:549–55.

    Article  PubMed  CAS  Google Scholar 

  38. Burnett AK, Russell NH, Kell J, et al. European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy. J Clin Oncol. 2010;28:2389–95.

    Article  PubMed  CAS  Google Scholar 

  39. Faderl S, Ravandi F, Huang X, et al. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008;112:1638–45.

    Article  PubMed  CAS  Google Scholar 

  40. Faderl S, Verstovsek S, Cortes J, et al. Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients 50 years of age or older. Blood. 2006;108:45–51.

    Article  PubMed  CAS  Google Scholar 

  41. Goldstone AH, Burnett AK, Wheatley K, et al. Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98:1302–11.

    Article  PubMed  CAS  Google Scholar 

  42. Mayer RJ, Davis RB, Schiffer CA, et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med. 1994;331:896–903.

    Article  PubMed  CAS  Google Scholar 

  43. Rowe JM. Consolidation therapy: what should be the standard of care? Best Pract Res Clin Haematol. 2008;21:53–60.

    Article  PubMed  CAS  Google Scholar 

  44. Lowenberg B, Suciu S, Archimbaud E, et al. Mitoxantrone versus daunorubicin in induction-consolidation chemotherapy–the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: final report. European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group. J Clin Oncol. 1998;16:872–81.

    PubMed  CAS  Google Scholar 

  45. Cahn JY, Labopin M, Sierra J, et al. No impact of high-dose cytarabine on the outcome of patients transplanted for acute myeloblastic leukaemia in first remission. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol. 2000;110:308–14.

    Article  PubMed  CAS  Google Scholar 

  46. Tallman MS, Rowlings PA, Milone G, et al. Effect of postremission chemotherapy before human leukocyte antigen-identical sibling transplantation for acute myelogenous leukemia in first complete remission. Blood. 2000;96:1254–8.

    PubMed  CAS  Google Scholar 

  47. Wallen H, Gooley TA, Deeg HJ, et al. Ablative allogeneic hematopoietic cell transplantation in adults 60 years of age and older. J Clin Oncol. 2005;23:3439–46.

    Article  PubMed  Google Scholar 

  48. Hegenbart U, Niederwieser D, Sandmaier BM, et al. Treatment for acute myelogenous leukemia by low-dose, total-body, irradiation-based conditioning and hematopoietic cell transplantation from related and unrelated donors. J Clin Oncol. 2006;24:444–53.

    Article  PubMed  CAS  Google Scholar 

  49. Shimoni A, Hardan I, Shem-Tov N, et al. Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensity. Leukemia. 2006;20:322–8.

    Article  PubMed  CAS  Google Scholar 

  50. Shimoni A, Hardan I, Shem-Tov N, et al. Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: long-term follow-up. Leukemia. 2010;24:1050–2.

    Article  PubMed  CAS  Google Scholar 

  51. McClune BL, Weisdorf DJ, Pedersen TL, et al. Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol. 2010;28:1878–87.

    Article  PubMed  Google Scholar 

  52. Koreth J, Aldridge J, Kim HT, et al. Reduced- intensity conditioning hematopoietic stem cell transplantation in patients over 60 years: hematologic malignancy outcomes are not impaired in advanced age. Biol Blood Marrow Transplant. 2010;16:792–800.

    Article  PubMed  Google Scholar 

  53. Ringden O, Labopin M, Ehninger G, et al. Reduced intensity conditioning compared with myeloablative conditioning using unrelated donor transplants in patients with acute myeloid leukemia. J Clin Oncol. 2009;27:4570–7.

    Article  PubMed  Google Scholar 

  54. Estey E, de Lima M, Tibes R, et al. Prospective feasibility analysis of reduced-intensity conditioning (RIC) regimens for hematopoietic stem cell transplantation (HSCT) in elderly patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Blood. 2007;109:1395–400.

    Article  PubMed  CAS  Google Scholar 

  55. Hourigan CS, Karp JE. Development of therapeutic agents for older patients with acute myelogenous leukemia. Curr Opin Investig Drugs. 2010;11:669–77.

    PubMed  CAS  Google Scholar 

  56. Schiller GJ, O’Brien SM, Pigneux A, et al. Single-agent laromustine, a novel alkylating agent, has significant activity in older patients with previously untreated poor-risk acute myeloid leukemia. J Clin Oncol. 2010;28:815–21.

    Article  PubMed  CAS  Google Scholar 

  57. Fehniger TA, Uy GL, Trinkaus K, et al. A phase II study of high dose lenalidomide as initial therapy for older patients with acute myeloid leukemia. Blood. 2011;117:1828–33.

    Google Scholar 

  58. Lancet JE, Gojo I, Gotlib J, et al. A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia. Blood. 2007;109:1387–94.

    Article  PubMed  CAS  Google Scholar 

  59. Harousseau JL, Martinelli G, Jedrzejczak WW, et al. A randomized phase 3 study of tipifarnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older. Blood. 2009;114:1166–73.

    Article  PubMed  CAS  Google Scholar 

  60. Correll PH, Paulson RF, Wei X. Molecular regulation of receptor tyrosine kinases in hematopoietic malignancies. Gene. 2006;374:26–38.

    Article  PubMed  CAS  Google Scholar 

  61. Fischer T, Stone RM, Deangelo DJ, et al. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010;28:4339–45.

    Article  PubMed  CAS  Google Scholar 

  62. Serve H, Wagner R, Sauerland C, et al. Sorafenib in combination with standard induction chemotherapy and consolidation therapy in elderly AML patients: results from a randomized, placebo-controlled Phase II trial. Presented at the ASH 52nd Annual Meeting Orlando, FL; December 3–7, 2010 2010, Abstract 333.

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Disclosure

R. Stone: Consultancy for Genzyme and Novartis; G. Motyckova: none.

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  1. Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA

    Gabriela Motyckova MD, PhD

  2. Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA

    Richard M. Stone MD

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  1. Gabriela Motyckova MD, PhD
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Correspondence to Richard M. Stone MD.

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Motyckova, G., Stone, R.M. Treatment of Elderly Acute Myeloid Leukemia Patients. Curr. Treat. Options in Oncol. 12, 341–353 (2011). https://doi.org/10.1007/s11864-011-0162-4

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