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01-08-2012 | Progress in Hematology

Acute myeloid leukemia in older adults

Authors: Masamitsu Yanada, Tomoki Naoe

Published in: International Journal of Hematology | Issue 2/2012

Abstract

Acute myeloid leukemia (AML) is predominantly a disease of older adults, with a median age at diagnosis of over 65 years. AML in older adults differs biologically and clinically from that in younger ones, and is characterized by stronger intrinsic resistance and lower tolerance to chemotherapy. The effects of age on both patient- and disease-related factors result in a higher incidence of early death during chemotherapy, a lower rate of complete remission, and a reduced chance of long-term survival. Treatment options for older adults with AML include intensive chemotherapy, less-intensive chemotherapy, best supportive care, or enrolment in clinical trials. Given the heterogeneous nature of AML in older adults, therapeutic decisions need to be individualized after systematic assessment of disease biology and patient characteristics. Regardless of treatment, however, outcomes for older AML patients remain in general unsatisfactory. In contrast with the progress made for younger adults, the treatment of AML in older adults has not improved significantly in recent decades. Development of less toxic and more targeted agents may well provide treatment alternatives for a majority of these patients. The overall dismal outcome with currently available treatment approaches has encouraged older AML patients to participate in prospective clinical trials.

Estey E. Acute myeloid leukemia and myelodysplastic syndromes in older patients. J Clin Oncol. 2007;25:1908–15.PubMedCrossRef

Dombret H, Raffoux E, Gardin C. Acute myeloid leukemia in the elderly. Semin Oncol. 2008;35:430–8.PubMedCrossRef

Pollyea DA, Kohrt HE, Medeiros BC. Acute myeloid leukaemia in the elderly: a review. Br J Haematol. 2011;152:524–42.PubMedCrossRef

Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, 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;115:453–74.PubMedCrossRef

O’Donnell MR, Abboud CN, Altman J, Appelbaum FR, Coutre SE, Damon LE, et al. Acute myeloid leukemia. J Natl Compr Cancer Netw. 2011;9:280–317.

Pulte D, Gondos A, Brenner H. Improvements in survival of adults diagnosed with acute myeloblastic leukemia in the early 21st century. Haematologica. 2008;93:594–600.PubMedCrossRef

Derolf AR, Kristinsson SY, Andersson TM, Landgren O, Dickman PW, Bjorkholm M. Improved patient survival for acute myeloid leukemia: a population-based study of 9729 patients diagnosed in Sweden between 1973 and 2005. Blood. 2009;113:3666–72.PubMedCrossRef

Grimwade D, Walker H, Harrison G, Oliver F, Chatters S, Harrison CJ, 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.PubMedCrossRef

Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, et al. Age and acute myeloid leukemia. Blood. 2006;107:3481–5.PubMedCrossRef

10.

Farag SS, Archer KJ, Mrozek K, Ruppert AS, Carroll AJ, Vardiman JW, 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.PubMedCrossRef

11.

Leith CP, Kopecky KJ, Chen IM, Eijdems L, Slovak ML, McConnell TS, et al. Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group Study. Blood. 1999;94:1086–99.PubMed

12.

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;162:1597–603.PubMedCrossRef

13.

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;106:1090–8.PubMedCrossRef

14.

Frohling S, Schlenk RF, Kayser S, Morhardt M, Benner A, Dohner K, 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.PubMedCrossRef

15.

Malfuson JV, Etienne A, Turlure P, de Revel T, Thomas X, Contentin N, et al. Risk factors and decision criteria for intensive chemotherapy in older patients with acute myeloid leukemia. Haematologica. 2008;93:1806–13.PubMedCrossRef

16.

Wheatley K, Brookes CL, Howman AJ, Goldstone AH, Milligan DW, Prentice AG, 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.PubMedCrossRef

17.

Rollig C, Thiede C, Gramatzki M, Aulitzky W, Bodenstein H, Bornhauser M, et al. A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial. Blood. 2010;116:971–8.PubMedCrossRef

18.

Scholl S, Theuer C, Scheble V, Kunert C, Heller A, Mugge LO, et al. Clinical impact of nucleophosmin mutations and Flt3 internal tandem duplications in patients older than 60 yr with acute myeloid leukaemia. Eur J Haematol. 2008;80:208–15.PubMedCrossRef

19.

Becker H, Marcucci G, Maharry K, Radmacher MD, Mrozek K, Margeson D, 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.PubMedCrossRef

20.

Whitman SP, Maharry K, Radmacher MD, Becker H, Mrozek K, Margeson D, 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.PubMedCrossRef

21.

Singh H, Asali S, Werner LL, DeAngelo DJ, Ballen KK, Amrein PC, et al. Outcome of older adults with cytogenetically normal AML (CN-AML) and FLT3 mutations. Leuk Res. 2011;35:1611–5.PubMedCrossRef

22.

de Jonge HJ, de Bont ES, Valk PJ, Schuringa JJ, Kies M, Woolthuis CM, et al. AML at older age: age-related gene expression profiles reveal a paradoxical down-regulation of p16INK4A mRNA with prognostic significance. Blood. 2009;114:2869–77.PubMedCrossRef

23.

Rao AV, Valk PJ, Metzeler KH, Acharya CR, Tuchman SA, Stevenson MM, et al. Age-specific differences in oncogenic pathway dysregulation and anthracycline sensitivity in patients with acute myeloid leukemia. J Clin Oncol. 2009;27:5580–6.PubMedCrossRef

24.

Giles FJ, Borthakur G, Ravandi F, Faderl S, Verstovsek S, Thomas D, 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;136:624–7.PubMedCrossRef

25.

Lowenberg 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;7:1268–74.PubMed

26.

Juliusson G, Antunovic P, Derolf A, Lehmann S, Mollgard L, Stockelberg D, 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.PubMedCrossRef

27.

Oshima K, Takahashi W, Asano-Mori Y, Izutsu K, Takahashi T, Arai Y, et al. Intensive chemotherapy for elderly patients with acute myelogeneous leukemia: a propensity score analysis by the Japan Hematology and Oncology Clinical Study Group (J-HOCS). Ann Hematol. 2012 May 11. [Epub ahead of print]

28.

Tilly H, Castaigne S, Bordessoule D, Casassus P, Le Prise PY, Tertian G, 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

29.

Lowenberg B, Suciu S, Archimbaud E, Ossenkoppele G, Verhoef GE, Vellenga E, et al. Use of recombinant GM-CSF during and after remission induction chemotherapy in patients aged 61 years and older with acute myeloid leukemia: final report of AML-11, a phase III randomized study of the Leukemia Cooperative Group of European Organisation for the Research and Treatment of Cancer and the Dutch Belgian Hemato-Oncology Cooperative Group. Blood. 1997;90:2952–61.PubMed

30.

Lowenberg B, Suciu S, Archimbaud E, Haak H, Stryckmans P, de Cataldo R, 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

31.

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;98:1302–11.PubMedCrossRef

32.

Anderson JE, Kopecky KJ, Willman CL, Head D, O’Donnell MR, Luthardt FW, 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;100:3869–76.PubMedCrossRef

33.

Baer MR, George SL, Dodge RK, O’Loughlin KL, Minderman H, Caligiuri MA, et al. Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood. 2002;100:1224–32.PubMed

34.

Schlenk RF, Frohling S, Hartmann F, Fischer JT, Glasmacher A, del Valle F, et al. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia. 2004;18:1798–803.PubMedCrossRef

35.

van der Holt B, Lowenberg B, Burnett AK, Knauf WU, Shepherd J, Piccaluga PP, et al. The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis. Blood. 2005;106:2646–54.PubMedCrossRef

36.

Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, 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;109:5129–35.PubMedCrossRef

37.

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;109:1114–24.PubMedCrossRef

38.

Pigneux A, Perreau V, Jourdan E, Vey N, Dastugue N, Huguet F, et al. Adding lomustine to idarubicin and cytarabine for induction chemotherapy in older patients with acute myeloid leukemia: the BGMT 95 trial results. Haematologica. 2007;92:1327–34.PubMedCrossRef

39.

Latagliata R, Breccia M, Fazi P, Iacobelli S, Martinelli G, Di Raimondo F, et al. Liposomal daunorubicin versus standard daunorubicin: long term follow-up of the GIMEMA GSI 103 AMLE randomized trial in patients older than 60 years with acute myelogenous leukaemia. Br J Haematol. 2008;143:681–9.PubMedCrossRef

40.

Burnett AK, Milligan D, Goldstone A, Prentice A, McMullin MF, Dennis M, et al. The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial. Br J Haematol. 2009;145:318–32.PubMedCrossRef

41.

Lowenberg 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;361:1235–48.PubMedCrossRef

42.

Harousseau JL, Martinelli G, Jedrzejczak WW, Brandwein JM, Bordessoule D, Masszi T, 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.PubMedCrossRef

43.

Pautas C, Merabet F, Thomas X, Raffoux E, Gardin C, Corm S, 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;28:808–14.PubMedCrossRef

44.

Cripe LD, Uno H, Paietta EM, Litzow MR, Ketterling RP, Bennett JM, et al. Zosuquidar, a novel modulator of P-glycoprotein, does not improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a randomized, placebo-controlled trial of the Eastern Cooperative Oncology Group 3999. Blood. 2010;116:4077–85.PubMedCrossRef

45.

Burnett AK, Hills RK, Hunter A, Milligan D, Kell J, Wheatley K, et al. The addition of arsenic trioxide to low-dose Ara-C in older patients with AML does not improve outcome. Leukemia. 2011;25:1122–7.PubMedCrossRef

46.

Castaigne S, Pautas C, Terre C, Raffoux E, Bordessoule D, Bastie JN, 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;379:1508–16.PubMedCrossRef

47.

Wakita A, Ohtake S, Takada S, Yagasaki F, Komatsu H, Miyazaki Y, et al. Randomized comparison of fixed-schedule versus response-oriented individualized induction therapy and use of ubenimex during and after consolidation therapy for elderly patients with acute myeloid leukemia: the JALSG GML200 Study. Int J Hematol. 2012 May 26. [Epub ahead of print]

48.

Stone RM, Berg DT, George SL, Dodge RK, Paciucci PA, Schulman PP, 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;98:548–53.PubMedCrossRef

49.

Buchner T, Hiddemann W, Berdel WE, Wormann B, Schoch C, Fonatsch C, et al. 6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group. J Clin Oncol. 2003;21:4496–504.PubMedCrossRef

50.

Schlenk RF, Frohling S, Hartmann F, Fischer JT, Glasmacher A, Del Valle 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;20:748–50.PubMedCrossRef

51.

Lowenberg B, Beck J, Graux C, van Putten W, Schouten HC, Verdonck LF, et al. Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study. Blood. 2010;115:2586–91.PubMedCrossRef

52.

McClune BL, Weisdorf DJ, Pedersen TL, Tunes da Silva G, Tallman MS, Sierra J, 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.PubMedCrossRef

Title: Acute myeloid leukemia in older adults
Authors: Masamitsu Yanada
Tomoki Naoe
Publication date: 01-08-2012
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 2/2012
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-012-1137-3

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