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Published in: Current Hematologic Malignancy Reports 2/2014

01-06-2014 | Acute Leukemias (F Ravandi, Section Editor)

Frontline Therapy of AML: Should the Older Patient be Treated Differently?

Author: James M. Foran

Published in: Current Hematologic Malignancy Reports | Issue 2/2014

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Abstract

Optimal treatment of acute myeloid leukemia (AML) in older adults (age ≥60 years) remains largely undefined, in part because of the inadequate response to available therapies, the poor prognosis relative to younger adults, the heterogeneity of the population, and the difficulty in determining who is fit for intensive therapy. In contrast to younger patients, there remains uncertainty about disease biology and molecular prognostic factors in elderly AML. While almost all patients may benefit from treatment, with the exception of reduced intensity allogeneic transplantation, there is little evidence that further intensifying therapy will improve outcomes. In fact, recent studies suggest that de-intensified treatment may in fact be superior and allow access to therapy for more patients. Both the disease and the patient must be approached holistically in order to make the best frontline treatment choice together. It is critical that we support well-designed clinical trials to develop more effective frontline therapies, develop more informative biomarkers, and to better understand who is a candidate for curative treatment.
Literature
1.
go back to reference 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;117(7):2137–45.PubMedCrossRef 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;117(7):2137–45.PubMedCrossRef
2.
go back to reference 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(5):1312–20.PubMedCrossRef 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(5):1312–20.PubMedCrossRef
4.
go back to reference 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(4):624–7.PubMedCrossRef 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(4):624–7.PubMedCrossRef
5.•
go back to reference 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(22):4422–9. This paper defines a group of Eldelry AML patients age >70 years who do not benefit from intensive therapy due to high induction mortality.PubMedCrossRef 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(22):4422–9. This paper defines a group of Eldelry AML patients age >70 years who do not benefit from intensive therapy due to high induction mortality.PubMedCrossRef
6.
7.
go back to reference Craig BM, Rollison DE, List AF, Cogle CR. Underreporting of myeloid malignancies by United States cancer registries. Cancer Epidemiol Biomarkers Prev. 2012;21(3):474–81.PubMedCentralPubMedCrossRef Craig BM, Rollison DE, List AF, Cogle CR. Underreporting of myeloid malignancies by United States cancer registries. Cancer Epidemiol Biomarkers Prev. 2012;21(3):474–81.PubMedCentralPubMedCrossRef
8.
go back to reference Linet MS, Devesa SS, Morgan GJ. The leukemias. In: Schottenfeld D, Fraumeni JF, editors. Cancer Epidemiology and Prevention. Thirdth ed. New York, NY: Oxford University Press; 2006. Linet MS, Devesa SS, Morgan GJ. The leukemias. In: Schottenfeld D, Fraumeni JF, editors. Cancer Epidemiology and Prevention. Thirdth ed. New York, NY: Oxford University Press; 2006.
9.
go back to reference Ross JA, Blair CK, Cerhan JR, et al. Nonsteroidal anti-inflammatory drug and acetaminophen use and risk of adult myeloid leukemia. Cancer Epidemiol Biomarkers Prev. 2011;20(8):1741–50.PubMedCentralPubMedCrossRef Ross JA, Blair CK, Cerhan JR, et al. Nonsteroidal anti-inflammatory drug and acetaminophen use and risk of adult myeloid leukemia. Cancer Epidemiol Biomarkers Prev. 2011;20(8):1741–50.PubMedCentralPubMedCrossRef
10.
go back to reference Weiss JR, Baker JA, Baer MR, Menezes RJ, Nowell S, Moysich KB. Opposing effects of aspirin and acetaminophen use on risk of adult acute leukemia. Leuk Res. 2006;30(2):164–9.PubMedCrossRef Weiss JR, Baker JA, Baer MR, Menezes RJ, Nowell S, Moysich KB. Opposing effects of aspirin and acetaminophen use on risk of adult acute leukemia. Leuk Res. 2006;30(2):164–9.PubMedCrossRef
11.
go back to reference Ross JA, Parker E, Blair CK, Cerhan JR, Folsom AR. Body mass index and risk of leukemia in older women. Cancer Epidemiol Biomarkers Prev. 2004;13(11 Pt 1):1810–3.PubMed Ross JA, Parker E, Blair CK, Cerhan JR, Folsom AR. Body mass index and risk of leukemia in older women. Cancer Epidemiol Biomarkers Prev. 2004;13(11 Pt 1):1810–3.PubMed
12.
go back to reference Larsson SC, Wolk A. Overweight and obesity and incidence of leukemia: a meta-analysis of cohort studies. Int J Cancer. 2008;122(6):1418–21.PubMedCrossRef Larsson SC, Wolk A. Overweight and obesity and incidence of leukemia: a meta-analysis of cohort studies. Int J Cancer. 2008;122(6):1418–21.PubMedCrossRef
13.
go back to reference Blair C, RM, Nguyen P, Cerhan J, Soler J, Ross J. Obesity at different times of life and the risk of AML. Proc 100th Annual Mtg of Am Assoc Cancer Res. 2009;82a. Blair C, RM, Nguyen P, Cerhan J, Soler J, Ross J. Obesity at different times of life and the risk of AML. Proc 100th Annual Mtg of Am Assoc Cancer Res. 2009;82a.
14.
go back to reference Moorman AV, Roman E, Cartwright RA, Morgan GJ. Smoking and the risk of acute myeloid leukaemia in cytogenetic subgroups. Br J Cancer. 2002;86(1):60–2.PubMedCentralPubMedCrossRef Moorman AV, Roman E, Cartwright RA, Morgan GJ. Smoking and the risk of acute myeloid leukaemia in cytogenetic subgroups. Br J Cancer. 2002;86(1):60–2.PubMedCentralPubMedCrossRef
15.
go back to reference Lichtman MA. Cigarette smoking, cytogenetic abnormalities, and acute myelogenous leukemia. Leukemia. 2007;21(6):1137–40.PubMedCrossRef Lichtman MA. Cigarette smoking, cytogenetic abnormalities, and acute myelogenous leukemia. Leukemia. 2007;21(6):1137–40.PubMedCrossRef
17.
go back to reference Hemminki K, Li X, Sundquist J, Sundquist K. Cancer risks in ulcerative colitis patients. Int J Cancer. 2008;123(6):1417–21.PubMedCrossRef Hemminki K, Li X, Sundquist J, Sundquist K. Cancer risks in ulcerative colitis patients. Int J Cancer. 2008;123(6):1417–21.PubMedCrossRef
19.
go back to reference Saberi Hosnijeh FCY, Peeters P, Romieu I, Xun W, Riboli E, Raaschou-Nielsen O, et al. Occupation and risk of lymphoid and myeloid leukaemia in the European Prospective Investigation into Cancer and Nutrition (EPIC). Occup Environ Med. 2013;70(7):464–70.PubMedCrossRef Saberi Hosnijeh FCY, Peeters P, Romieu I, Xun W, Riboli E, Raaschou-Nielsen O, et al. Occupation and risk of lymphoid and myeloid leukaemia in the European Prospective Investigation into Cancer and Nutrition (EPIC). Occup Environ Med. 2013;70(7):464–70.PubMedCrossRef
20.
go back to reference Sinner PJ, Cerhan JR, Folsom AR, Ross JA. Positive association of farm or rural residence with acute myeloid leukemia incidence in a cohort of older women. Cancer Epidemiol Biomarkers Prev. 2005;14(10):2446–8.PubMedCrossRef Sinner PJ, Cerhan JR, Folsom AR, Ross JA. Positive association of farm or rural residence with acute myeloid leukemia incidence in a cohort of older women. Cancer Epidemiol Biomarkers Prev. 2005;14(10):2446–8.PubMedCrossRef
21.
go back to reference Lang K, Earle CC, Foster T, Dixon D, Van Gool R, Menzin J. Trends in the treatment of acute myeloid leukaemia in the elderly. Drugs Aging. 2005;22(11):943–55.PubMedCrossRef Lang K, Earle CC, Foster T, Dixon D, Van Gool R, Menzin J. Trends in the treatment of acute myeloid leukaemia in the elderly. Drugs Aging. 2005;22(11):943–55.PubMedCrossRef
22.
go back to reference Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007;356(4):348–59.PubMedCrossRef Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007;356(4):348–59.PubMedCrossRef
23.•
go back to reference 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(11):1878–87. Demonstrates that increasing age does not predict worse outcome in patients selected for non-myeloablative allogeneic transplantation from an unrelated donor. 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(11):1878–87. Demonstrates that increasing age does not predict worse outcome in patients selected for non-myeloablative allogeneic transplantation from an unrelated donor.
24.•
go back to reference 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(6):1114–24. This was the first study to show a clear survival advantage of low intensity therapy with LDAC for intermediate risk AML over supportive care.PubMedCrossRef 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(6):1114–24. This was the first study to show a clear survival advantage of low intensity therapy with LDAC for intermediate risk AML over supportive care.PubMedCrossRef
25.•
go back to reference 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(4):562–9. Important subgroup analysis of the AZA-001 study showing a survival advantage of azacitidine over conventional care regimens in pateints with 20–30 % blasts. PubMedCrossRef 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(4):562–9. Important subgroup analysis of the AZA-001 study showing a survival advantage of azacitidine over conventional care regimens in pateints with 20–30 % blasts. PubMedCrossRef
26.
go back to reference Kornblith AB, Herndon 2nd JE, Silverman LR, et al. Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study. J Clin Oncol. 2002;20(10):2441–52.PubMedCrossRef Kornblith AB, Herndon 2nd JE, Silverman LR, et al. Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study. J Clin Oncol. 2002;20(10):2441–52.PubMedCrossRef
27.
go back to reference Gardin C, Chevret S, Pautas C, et al. Superior long-term outcome with idarubicin compared with high-dose daunorubicin in patients with acute myeloid leukemia age 50 years and older. J Clin Oncol. 2013;31(3):321–7.PubMedCrossRef Gardin C, Chevret S, Pautas C, et al. Superior long-term outcome with idarubicin compared with high-dose daunorubicin in patients with acute myeloid leukemia age 50 years and older. J Clin Oncol. 2013;31(3):321–7.PubMedCrossRef
28.
go back to reference 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(2):272–9.PubMed 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(2):272–9.PubMed
29.
go back to reference 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(9):1268–74.PubMed 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(9):1268–74.PubMed
30.•
go back to reference 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(18):4179–87. This population-based registry demonstrated a survival advantage for patients age 70–79 years treated with the intent of achieving a remission (in Sweden). 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(18):4179–87. This population-based registry demonstrated a survival advantage for patients age 70–79 years treated with the intent of achieving a remission (in Sweden).
31.
go back to reference 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(10):1766–71.PubMedCentralPubMedCrossRef 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(10):1766–71.PubMedCentralPubMedCrossRef
32.
go back to reference Denzlinger C, Bowen D, Benz D, Gelly K, Brugger W, Kanz L. Low-dose melphalan induces favourable responses in elderly patients with high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia. Br J Haematol. 2000;108(1):93–5.PubMedCrossRef Denzlinger C, Bowen D, Benz D, Gelly K, Brugger W, Kanz L. Low-dose melphalan induces favourable responses in elderly patients with high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia. Br J Haematol. 2000;108(1):93–5.PubMedCrossRef
33.
go back to reference 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(3):872–81.PubMed 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(3):872–81.PubMed
34.
go back to reference 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(5):598–605.PubMedCrossRef 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(5):598–605.PubMedCrossRef
35.
go back to reference Krug U, Rollig C, Koschmieder A, et al. Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes. Lancet. 2010;376(9757):2000–8.PubMedCrossRef Krug U, Rollig C, Koschmieder A, et al. Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes. Lancet. 2010;376(9757):2000–8.PubMedCrossRef
36.
go back to reference Klepin HD, Geiger AM, Tooze JA, et al. Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia. Blood. 2013;121(21):4287–94.PubMedCentralPubMedCrossRef Klepin HD, Geiger AM, Tooze JA, et al. Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia. Blood. 2013;121(21):4287–94.PubMedCentralPubMedCrossRef
37.
go back to reference Sherman AE, Motyckova G, Fega KR, et al. Geriatric assessment in older patients with acute myeloid leukemia: a retrospective study of associated treatment and outcomes. Leuk Res. 2013;37(9):998–1003.PubMedCrossRef Sherman AE, Motyckova G, Fega KR, et al. Geriatric assessment in older patients with acute myeloid leukemia: a retrospective study of associated treatment and outcomes. Leuk Res. 2013;37(9):998–1003.PubMedCrossRef
38.
go back to reference Bertoli S, Berard E, Huguet F, et al. Time from diagnosis to intensive chemotherapy initiation does not adversely impact the outcome of patients with acute myeloid leukemia. Blood. 2013;121(14):2618–26.PubMedCrossRef Bertoli S, Berard E, Huguet F, et al. Time from diagnosis to intensive chemotherapy initiation does not adversely impact the outcome of patients with acute myeloid leukemia. Blood. 2013;121(14):2618–26.PubMedCrossRef
39.•
go back to reference Patel JP, Gonen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366(12):1079–89. ECOG study showed the prevalance and clinical impact of occult mutations io younger AML patients receiving intensive treatment. Patel JP, Gonen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366(12):1079–89. ECOG study showed the prevalance and clinical impact of occult mutations io younger AML patients receiving intensive treatment.
40.•
go back to reference Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–74. Landmark paper from The Cancer Genome Atlas establishing incidence of baseline genetic lesions in AML. Its direct relevance to the large populations of Elderly AML patients remains a question. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–74. Landmark paper from The Cancer Genome Atlas establishing incidence of baseline genetic lesions in AML. Its direct relevance to the large populations of Elderly AML patients remains a question.
41.
go back to reference Stirewalt DL, Kopecky KJ, Meshinchi S, et al. FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood. 2001;97(11):3589–95.PubMedCrossRef Stirewalt DL, Kopecky KJ, Meshinchi S, et al. FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood. 2001;97(11):3589–95.PubMedCrossRef
42.
go back to reference Schlenk RF, Dohner K, Kneba M, et al. Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. Results from the AMLSG Trial AML HD98B. Haematologica. 2009;94(1):54–60.PubMedCentralPubMedCrossRef Schlenk RF, Dohner K, Kneba M, et al. Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. Results from the AMLSG Trial AML HD98B. Haematologica. 2009;94(1):54–60.PubMedCentralPubMedCrossRef
43.
go back to reference Rollig C, Bornhauser M, Thiede C, et al. Long-term prognosis of acute myeloid leukemia according to the new genetic risk classification of the European LeukemiaNet recommendations: evaluation of the proposed reporting system. J Clin Oncol. 2011;29(20):2758–65.PubMedCrossRef Rollig C, Bornhauser M, Thiede C, et al. Long-term prognosis of acute myeloid leukemia according to the new genetic risk classification of the European LeukemiaNet recommendations: evaluation of the proposed reporting system. J Clin Oncol. 2011;29(20):2758–65.PubMedCrossRef
44.
go back to reference Ferrara F, Criscuolo C, Riccardi C, et al. FLT3 mutations have no prognostic impact in elderly patients with acute myeloid leukemia and normal karyotype. Am J Hematol. 2009;84(8):532–5.PubMedCrossRef Ferrara F, Criscuolo C, Riccardi C, et al. FLT3 mutations have no prognostic impact in elderly patients with acute myeloid leukemia and normal karyotype. Am J Hematol. 2009;84(8):532–5.PubMedCrossRef
45.
go back to reference Su L, Li X, Gao SJ, et al. Cytogenetic and genetic mutation features of de novo acute myeloid leukemia in elderly chinese patients. Asian Pac J Cancer Prev. 2014;15(2):895–8.PubMed Su L, Li X, Gao SJ, et al. Cytogenetic and genetic mutation features of de novo acute myeloid leukemia in elderly chinese patients. Asian Pac J Cancer Prev. 2014;15(2):895–8.PubMed
46.
go back to reference 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(18):3622–6.PubMedCentralPubMedCrossRef 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(18):3622–6.PubMedCentralPubMedCrossRef
47.
go back to reference 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(4):596–604.PubMedCentralPubMedCrossRef 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(4):596–604.PubMedCentralPubMedCrossRef
48.
go back to reference Nazha A, Bueso-Ramos C, Estey E, et al. The addition of all-trans retinoic acid to chemotherapy may not improve the outcome of patient with NPM1 mutated acute myeloid leukemia. Front Oncol. 2013;3:218.PubMedCentralPubMedCrossRef Nazha A, Bueso-Ramos C, Estey E, et al. The addition of all-trans retinoic acid to chemotherapy may not improve the outcome of patient with NPM1 mutated acute myeloid leukemia. Front Oncol. 2013;3:218.PubMedCentralPubMedCrossRef
49.
go back to reference Marcucci G, Metzeler KH, Schwind S, et al. Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia. J Clin Oncol. 2012;30(7):742–50.PubMedCentralPubMedCrossRef Marcucci G, Metzeler KH, Schwind S, et al. Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia. J Clin Oncol. 2012;30(7):742–50.PubMedCentralPubMedCrossRef
50.
go back to reference Marcucci G, Yan P, Maharry K, et al. Epigenetics meets genetics in acute myeloid leukemia: clinical impact of a novel seven-gene score. J Clin Oncol. 2014;32(6):548–56.PubMedCrossRef Marcucci G, Yan P, Maharry K, et al. Epigenetics meets genetics in acute myeloid leukemia: clinical impact of a novel seven-gene score. J Clin Oncol. 2014;32(6):548–56.PubMedCrossRef
51.
go back to reference Rowe JM, Neuberg D, Friedenberg W, et al. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004;103(2):479–85.PubMedCrossRef Rowe JM, Neuberg D, Friedenberg W, et al. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004;103(2):479–85.PubMedCrossRef
52.
go back to reference Goldstone AH, Burnett AK, Wheatley K, Smith AG, Hutchinson RM, Clark RE. 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(5):1302–11.PubMedCrossRef Goldstone AH, Burnett AK, Wheatley K, Smith AG, Hutchinson RM, Clark RE. 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(5):1302–11.PubMedCrossRef
53.
go back to reference Anderson JE, Kopecky KJ, Willman CL, et al. Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study. Blood. 2002;100(12):3869–76.PubMedCrossRef Anderson JE, Kopecky KJ, Willman CL, et al. Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study. Blood. 2002;100(12):3869–76.PubMedCrossRef
54.
go back to reference Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009;361(13):1249–59.PubMedCrossRef Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009;361(13):1249–59.PubMedCrossRef
55.
go back to reference 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(13):1235–48.PubMedCrossRef 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(13):1235–48.PubMedCrossRef
56.
go back to reference Attar EC, Johnson JL, Amrein PC, et al. Bortezomib added to daunorubicin and cytarabine during induction therapy and to intermediate-dose cytarabine for consolidation in patients with previously untreated acute myeloid leukemia age 60 to 75 years: CALGB (Alliance) study 10502. J Clin Oncol. 2013;31(7):923–9.PubMedCentralPubMedCrossRef Attar EC, Johnson JL, Amrein PC, et al. Bortezomib added to daunorubicin and cytarabine during induction therapy and to intermediate-dose cytarabine for consolidation in patients with previously untreated acute myeloid leukemia age 60 to 75 years: CALGB (Alliance) study 10502. J Clin Oncol. 2013;31(7):923–9.PubMedCentralPubMedCrossRef
57.
go back to reference Kim I, Koh Y, Yoon SS, et al. Fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) combination therapy for elderly acute myeloid leukemia patients. Am J Hematol. 2013;88(1):10–5.PubMedCrossRef Kim I, Koh Y, Yoon SS, et al. Fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) combination therapy for elderly acute myeloid leukemia patients. Am J Hematol. 2013;88(1):10–5.PubMedCrossRef
58.
go back to reference 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(5):1090–8.PubMedCrossRef 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(5):1090–8.PubMedCrossRef
59.
go back to reference 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(1):63–73.PubMedCentralPubMedCrossRef 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(1):63–73.PubMedCentralPubMedCrossRef
60.
go back to reference 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(14):2389–95.PubMedCrossRef 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(14):2389–95.PubMedCrossRef
61.
go back to reference 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(4):549–55.PubMedCrossRef 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(4):549–55.PubMedCrossRef
62.
go back to reference Burnett AK, Russell NH, Hills RK, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012;30(32):3924–31.PubMedCrossRef Burnett AK, Russell NH, Hills RK, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012;30(32):3924–31.PubMedCrossRef
63.
go back to reference 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(9825):1508–16.PubMedCrossRef 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(9825):1508–16.PubMedCrossRef
64.
go back to reference Amadori S, Suciu S, Stasi R, et al. Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17). J Clin Oncol. 2013;31(35):4424–30.PubMedCrossRef Amadori S, Suciu S, Stasi R, et al. Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17). J Clin Oncol. 2013;31(35):4424–30.PubMedCrossRef
65.
go back to reference Thépot S, Itzykson R, Seegers V, et al. Azacitidine in untreated acute myeloid leukemia: a report on 149 patients. Am J Hematol. 2014;89(4):410–6. Thépot S, Itzykson R, Seegers V, et al. Azacitidine in untreated acute myeloid leukemia: a report on 149 patients. Am J Hematol. 2014;89(4):410–6.
66.
go back to reference van der Helm LH, Veeger NJ, Kooy M, et al. Azacitidine results in comparable outcome in newly diagnosed AML patients with more or less than 30 % bone marrow blasts. Leuk Res. 2013;37(8):877–82.PubMedCrossRef van der Helm LH, Veeger NJ, Kooy M, et al. Azacitidine results in comparable outcome in newly diagnosed AML patients with more or less than 30 % bone marrow blasts. Leuk Res. 2013;37(8):877–82.PubMedCrossRef
67.
go back to reference Blum W, Garzon R, Klisovic RB, et al. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010;107(16):7473–8.PubMedCentralPubMedCrossRef Blum W, Garzon R, Klisovic RB, et al. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010;107(16):7473–8.PubMedCentralPubMedCrossRef
68.
go back to reference Cashen AF, Schiller GJ, O’Donnell MR, DiPersio JF. Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol. 2010;28(4):556–61.PubMedCrossRef Cashen AF, Schiller GJ, O’Donnell MR, DiPersio JF. Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol. 2010;28(4):556–61.PubMedCrossRef
69.
go back to reference 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(21):2670–7.PubMedCrossRef 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(21):2670–7.PubMedCrossRef
70.
go back to reference Craddock C, Quek L, Goardon N, et al. Azacitidine fails to eradicate leukemic stem/progenitor cell populations in patients with acute myeloid leukemia and myelodysplasia. Leukemia. 2013;27(5):1028–36.PubMedCrossRef Craddock C, Quek L, Goardon N, et al. Azacitidine fails to eradicate leukemic stem/progenitor cell populations in patients with acute myeloid leukemia and myelodysplasia. Leukemia. 2013;27(5):1028–36.PubMedCrossRef
71.
go back to reference 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(1):75–81.PubMedCrossRef 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(1):75–81.PubMedCrossRef
72.
go back to reference 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(4):519–22.PubMedCrossRef 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(4):519–22.PubMedCrossRef
73.
go back to reference Burnett AK, Hills RK, Hunter A, et al. The addition of arsenic trioxide to low-dose Ara-C in older patients with AML does not improve outcome. Leukemia. 2011;25(7):1122–7.PubMedCrossRef Burnett AK, Hills RK, Hunter A, et al. The addition of arsenic trioxide to low-dose Ara-C in older patients with AML does not improve outcome. Leukemia. 2011;25(7):1122–7.PubMedCrossRef
74.
go back to reference Macdonald DA, Assouline SE, Brandwein J, et al. A phase I/II study of sorafenib in combination with low dose cytarabine in elderly patients with acute myeloid leukemia or high-risk myelodysplastic syndrome from the National Cancer Institute of Canada Clinical Trials Group: trial IND.186. Leuk Lymphoma. 2013;54(4):760–6.PubMedCrossRef Macdonald DA, Assouline SE, Brandwein J, et al. A phase I/II study of sorafenib in combination with low dose cytarabine in elderly patients with acute myeloid leukemia or high-risk myelodysplastic syndrome from the National Cancer Institute of Canada Clinical Trials Group: trial IND.186. Leuk Lymphoma. 2013;54(4):760–6.PubMedCrossRef
75.
go back to reference Ravandi F, Alattar ML, Grunwald MR, et al. Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation. Blood. 2013;121(23):4655–62.PubMedCrossRef Ravandi F, Alattar ML, Grunwald MR, et al. Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation. Blood. 2013;121(23):4655–62.PubMedCrossRef
76.
go back to reference Cortes JE, Kantarjian H, Foran JM, et al. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol. 2013;31(29):3681–7.PubMedCrossRef Cortes JE, Kantarjian H, Foran JM, et al. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol. 2013;31(29):3681–7.PubMedCrossRef
77.
go back to reference 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(24):4840–5.PubMedCentralPubMedCrossRef 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(24):4840–5.PubMedCentralPubMedCrossRef
78.•
go back to reference Burnett AK, Russell NH, Hunter AE, et al. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013;122(8):1384–94. Despite increasing the CR rate, clofarabine did not increase survival compared with LDAC, suggesting that CR is not an adequate surrogate endopint, and that we have still not optimally defined appropriate patients for lower versus higher intensity traement. Burnett AK, Russell NH, Hunter AE, et al. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013;122(8):1384–94. Despite increasing the CR rate, clofarabine did not increase survival compared with LDAC, suggesting that CR is not an adequate surrogate endopint, and that we have still not optimally defined appropriate patients for lower versus higher intensity traement.
79.
go back to reference Hahn T, McCarthy Jr PL, Hassebroek A, et al. Significant improvement in survival after allogeneic hematopoietic cell transplantation during a period of significantly increased use, older recipient age, and use of unrelated donors. J Clin Oncol. 2013;31(19):2437–49.PubMedCrossRef Hahn T, McCarthy Jr PL, Hassebroek A, et al. Significant improvement in survival after allogeneic hematopoietic cell transplantation during a period of significantly increased use, older recipient age, and use of unrelated donors. J Clin Oncol. 2013;31(19):2437–49.PubMedCrossRef
80.
go back to reference Mawad R, Gooley TA, Sandhu V, et al. Frequency of allogeneic hematopoietic cell transplantation among patients with high- or intermediate-risk acute myeloid leukemia in first complete remission. J Clin Oncol. 2013;31(31):3883–8.PubMedCrossRef Mawad R, Gooley TA, Sandhu V, et al. Frequency of allogeneic hematopoietic cell transplantation among patients with high- or intermediate-risk acute myeloid leukemia in first complete remission. J Clin Oncol. 2013;31(31):3883–8.PubMedCrossRef
81.
go back to reference Devine SM, Owza K, Blum W, et al. A Phase II Study of Allogeneic Transplantation for Older Patients with AML in First Complete Remission Using a Reduced Intensity Conditioning Regimen: Results From CALGB 100103/BMT CTN 0502. Blood (Proc ASH). 2012;120:230a. Devine SM, Owza K, Blum W, et al. A Phase II Study of Allogeneic Transplantation for Older Patients with AML in First Complete Remission Using a Reduced Intensity Conditioning Regimen: Results From CALGB 100103/BMT CTN 0502. Blood (Proc ASH). 2012;120:230a.
Metadata
Title
Frontline Therapy of AML: Should the Older Patient be Treated Differently?
Author
James M. Foran
Publication date
01-06-2014
Publisher
Springer US
Published in
Current Hematologic Malignancy Reports / Issue 2/2014
Print ISSN: 1558-8211
Electronic ISSN: 1558-822X
DOI
https://doi.org/10.1007/s11899-014-0211-8

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