Acute myeloid leukemia in the elderly: do we know who should be treated and how?

References

• Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin 2006;56:106–130.
   PubMed Web of Science ®Google Scholar
• Lowenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N Engl J Med 1999;341:1051–1062.
   PubMed Web of Science ®Google Scholar
• Juliusson G, Lazarevic V, Horstedt AS, et al. Acute myeloid leukemia in the real world: why population-based registries are needed. Blood 2012;119:3890–3899.
   PubMed Web of Science ®Google Scholar
• Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood 2006;107:3481–3485.
   PubMed Web of Science ®Google Scholar
• 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;27:61–69.
   PubMed Web of Science ®Google Scholar
• Grimwade D, Walker H, Oliver F, et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood 1998;92:2322–2333.
   PubMed Web of Science ®Google Scholar
• 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;98:1312–1320.
   PubMed Web of Science ®Google Scholar
• Byrd JC, Mrozek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002;100:4325–4336.
   PubMed Web of Science ®Google Scholar
• Kantarjian H, O’Brien S, Cortes J, 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;106:1090–1098.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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;108:3280–3288.
   PubMed Web of Science ®Google Scholar
• van der Holt B, Breems DA, Berna Beverloo H, et al. Various distinctive cytogenetic abnormalities in patients with acute myeloid leukaemia aged 60 years and older express adverse prognostic value: results from a prospective clinical trial. Br J Haematol 2007;136: 96–105.
   PubMed Web of Science ®Google Scholar
• 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;116:354–365.
   PubMed Web of Science ®Google Scholar
• Sekeres MA, Stone RM, Zahrieh D, et al. Decision-making and quality of life in older adults with acute myeloid leukemia or advanced myelodysplastic syndrome. Leukemia 2004;18:809–816.
   PubMed Web of Science ®Google Scholar
• Malfuson JV, Etienne A, Turlure P, et al. Risk factors and decision criteria for intensive chemotherapy in older patients with acute myeloid leukemia. Haematologica 2008;93:1806–1813.
   PubMed Web of Science ®Google Scholar
• Schlenk RF, Dohner K, Krauter J, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 2008;358:1909–1918.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Marcucci G, Haferlach T, Dohner H. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. J Clin Oncol 2011;29:475–486.
   PubMed Web of Science ®Google Scholar
• Santos FP, Jones D, Qiao W, et al. Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia. Cancer 2011;117:2145–2155.
   PubMed Web of Science ®Google Scholar
• Schnittger S, Schoch C, Dugas M, et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood 2002;100:59–66.
   PubMed Web of Science ®Google Scholar
• Pemmaraju N, Kantarjian H, Ravandi F, et al. FLT3 inhibitors in the treatment of acute myeloid leukemia: the start of an era?Cancer 2011;117:3293–3304.
   PubMed Web of Science ®Google Scholar
• Leith CP, Kopecky KJ, Godwin J, et al. Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study. Blood 1997;89:3323–3329.
   PubMed Web of Science ®Google Scholar
• Hutchins LF, Unger JM, Crowley JJ, et al. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 1999;341:2061–2067.
   PubMed Web of Science ®Google Scholar
• Menzin J, Lang K, Earle CC, et al. The outcomes and costs of acute myeloid leukemia among the elderly. Arch Intern Med 2002;162: 1597–1603.
   PubMed Web of Science ®Google Scholar
• Juliusson G, Billstrom R, Gruber A, et al. Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival. Leukemia 2006;20:42–47.
   PubMed Web of Science ®Google Scholar
• 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;7:1268–1274.
   PubMed Web of Science ®Google Scholar
• 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;109:1114–1124.
   PubMed Web of Science ®Google Scholar
• Giles FJ, Borthakur G, Ravandi F, et al. The haematopoietic cell transplantation comorbidity index score is predictive of early death and survival in patients over 60 years of age receiving induction therapy for acute myeloid leukaemia. Br J Haematol 2007;136:624–627.
   PubMed Web of Science ®Google Scholar
• Yates J, Glidewell O, Wiernik P, et al. Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood 1982;60:454–462.
   PubMed Web of Science ®Google Scholar
• Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med 2009;361:1249–1259.
   PubMed Web of Science ®Google Scholar
• Lowenberg B, Ossenkoppele GJ, van Putten W, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med 2009;361:1235–1248.
   PubMed Web of Science ®Google Scholar
• Pautas C, Merabet F, Thomas X, et al. Randomized study of intensified anthracycline doses for induction and recombinant interleukin-2 for maintenance in patients with acute myeloid leukemia age 50 to 70 years: results of the ALFA-9801 Study. J Clin Oncol 2010;28:808–814.
   PubMed Web of Science ®Google Scholar
• 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;8:272–279.
   PubMed Web of Science ®Google Scholar
• 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;98:1302–1311.
   PubMed Web of Science ®Google Scholar
• Stone RM, Berg DT, George SL, et al. Postremission therapy in older patients with de novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine. Blood 2001;98:548–553.
   PubMed Web of Science ®Google Scholar
• Gardin C, Turlure P, Fagot T, et al. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood 2007;109:5129–5135.
   PubMed Web of Science ®Google Scholar
• Schlenk RF, Frohling S, Hartmann F, et al. Intensive consolidation versus oral maintenance therapy in patients 61 years or older with acute myeloid leukemia in first remission: results of second randomization of the AML HD98-B treatment trial. Leukemia 2006;20:748–750.
   PubMed Web of Science ®Google Scholar
• Sievers EL, Larson RA, Stadtmauer EA, et al. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol 2001;19:3244–3254.
   PubMed Web of Science ®Google Scholar
• Larson RA, Sievers EL, Stadtmauer EA, et al. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer 2005;104:1442–1452.
   PubMed Web of Science ®Google Scholar
• Estey EH, Thall PF, Giles FJ, et al. Gemtuzumab ozogamicin with or without interleukin 11 in patients 65 years of age or older with untreated acute myeloid leukemia and high-risk myelodysplastic syndrome: comparison with idarubicin plus continuous-infusion, high-dose cytosine arabinoside. Blood 2002;99:4343–4349.
   PubMed Web of Science ®Google Scholar
• Burnett AK, Hills RK, Hunter AE, et al. The addition of gemtuzumab ozogamicin to low-dose Ara-C improves remission rate but does not significantly prolong survival in older patients with acute myeloid leukaemia: results from the LRF AML14 and NCRI AML16 pick-a-winner comparison. Leukemia 2013;27:75–81.
   PubMed Web of Science ®Google Scholar
• Castaigne S, Pautas C, Terre C, 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;379:1508–1516.
   PubMed Web of Science ®Google Scholar
• 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;109:1387–1394.
   PubMed Web of Science ®Google Scholar
• 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;114:1166–1173.
   PubMed Web of Science ®Google Scholar
• Karp JE, Flatten K, Feldman EJ, et al. Active oral regimen for elderly adults with newly diagnosed acute myelogenous leukemia: a preclinical and phase 1 trial of the farnesyltransferase inhibitor tipifarnib (R115777, Zarnestra) combined with etoposide. Blood 2009;113:4841–4852.
   PubMed Web of Science ®Google Scholar
• Burnett AK, Russell NH, Culligan D, et al. The addition of the farnesyl transferase inhibitor, tipifarnib, to low dose cytarabine does not improve outcome for older patients with AML. Br J Haematol 2012;158:519–522.
   PubMed Web of Science ®Google Scholar
• Luger S ZL, Paietta E, et al. R115777 (tipifarnib) improves early survival when used as maintenance therapy for elderly or relapsed/refractory patients with acute myelogenous leukemia in remission. Blood 2012;120(Suppl. 1):Abstract 676.
   Google Scholar
• 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;28:549–555.
   PubMed Web of Science ®Google Scholar
• Burnett A, Russel NH, McMullin M, et al. A randomised comparison of clofarabine versus low dose Ara-C as first line treatment for older patients with AML. Blood 2012;120(Suppl. 1): Abstract 889.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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;112:1638–1645.
   PubMed Web of Science ®Google Scholar
• Faderl S, Wetzler M, Rizzieri D, et al. Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I trial. J Clin Oncol 2012;30:2492–2499.
   PubMed Web of Science ®Google Scholar
• Faderl S, Ravandi F, Huang X, et al. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer 2012;118:4471–4477.
   PubMed Web of Science ®Google Scholar
• Burnett A, Russel NH, Kell J, et al. A comparison of daunorubicin/Ara-C (DA) versus daunorubicin/clofarabine (DClo) and two versus three courses of total treatment for older patients with AML and high risk MDS: results of the UK NCRI AML16 trial. Blood 2012;120(Suppl. 1): Abstract 892.
   PubMed Web of Science ®Google Scholar
• 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;28:562–569.
   PubMed Web of Science ®Google Scholar
• Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol 2012;30:2670–2677.
   PubMed Web of Science ®Google Scholar
• Quintas-Cardama A, Ravandi F, Liu-Dumlao T, et al. Epigenetic therapy is associated with similar survival compared with intensive chemotherapy in older patients with newly diagnosed acute myeloid leukemia. Blood 2012;120:4840–4845.
   PubMed Web of Science ®Google Scholar
• Slovak ML, Kopecky KJ, Cassileth PA, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 2000;96:4075–4083.
   PubMed Web of Science ®Google Scholar
• Azuma A, Huang P, Matsuda A, et al. 2’-C-cyano-2’-deoxy-1-beta-D-arabino-pentofuranosylcytosine: a novel anticancer nucleoside analog that causes both DNA strand breaks and G(2) arrest. Mol Pharmacol 2001;59:725–731.
   PubMed Web of Science ®Google Scholar
• Kantarjian H, Faderl S, Garcia-Manero G, et al. Oral sapacitabine for the treatment of acute myeloid leukaemia in elderly patients: a randomised phase 2 study. Lancet Oncol 2012;13:1096–1104.
   PubMed Web of Science ®Google Scholar
• 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;28:815–821.
   PubMed Web of Science ®Google Scholar
• Lancet JE. Cortes JE, Kovacsovics T, et al. A comparison of CR versus CRi response following CPX-351 treatment of newly diagnosed AML in elderly patients (pts). J Clin Oncol 2012;30(Suppl. 1): Abstract 6601.
   Google Scholar
• Cortes J, Feldman E, Yee K, et al. Two dosing regimens of tosedostat in elderly patients with relapsed or refractory acute myeloid leukaemia (OPAL): a randomised open-label phase 2 study. Lancet Oncol 2013;14:354–362.
   PubMed Web of Science ®Google Scholar
• Mathisen MS, Ravandi F. Efficacy of tosedostat, a novel, oral agent for elderly patients with relapsed or refractory acute myeloid leukemia: a review of the phase II OPAL trial. Future Oncol 2012;8:351–357.
   PubMed Web of Science ®Google Scholar
• Giralt S. Allografting older patients--myths and realities. Biol Blood Marrow Transplant 2009;15:146–148.
   PubMed Web of Science ®Google Scholar
• 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;109:1395–1400.
   PubMed Web of Science ®Google Scholar
• Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010;115:453–474.
   PubMed Web of Science ®Google Scholar