Treatment decision-making for older patients with high-risk myelodysplastic syndrome or acute myeloid leukemia: Problems and approaches

Haematologica

Volumn 91, Issue 11, 2006, Pages 1513-1522

  Deschler, Barbara ^a   De Witte, Theo ^b   Mertelsmann, Roland ^a   Lübbert, Michael ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

^b RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Allogeneic transplantation; Comorbidity; Geriatric assessment; Induction chemotherapy

Indexed keywords

ACUTE GRANULOCYTIC LEUKEMIA; AGED; CANCER REGRESSION; CANCER SURVIVAL; CLINICAL PRACTICE; GERIATRIC ASSESSMENT; HUMAN; MEDICAL DECISION MAKING; MYELODYSPLASTIC SYNDROME; PALLIATIVE THERAPY; PHYSICIAN; PROGNOSIS; REVIEW;

AGE FACTORS; AGED; DECISION MAKING; HUMANS; LEUKEMIA, MYELOCYTIC, ACUTE; MYELODYSPLASTIC SYNDROMES; PROBLEM SOLVING; RISK FACTORS; TREATMENT OUTCOME;

EID: 33750949551     PISSN: 03906078     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (120)

1. Aul C, Germing U, Gattermann N, Minning H. Increasing incidence of myelodysplastic syndromes: real or fictitious? Leuk Res 1998;22:93-100.
2. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997;89:2079-88.
3. Pinto A, Zagonel V. 5-Aza-2′-deoxycytidine (decitabine) and 5-azacytidine in the treatment of acute myeloid leukemias and myelodysplastic syndromes: past, present and future trends. Leukemia 1993;7 Suppl 1:51-60.
4. Shimamoto T, Tohyama K, Okamoto T, Uchiyama T, Mori H, Tomonaga M, et al. Cyclosporin A therapy for patients with myelodysplastic syndrome: multicenter pilot studies in Japan. Leuk Res 2003;27:783-8.
5. Sekeres MA, Stone RM, Zahrieh D, Neuberg D, Morrison V, De Angelo DJ, et al. Decision-making and quality of life in older adults with acute myeloid leukemia or advanced myelodysplastic syndrome. Leukemia 2004;18:809-16.
6. Ries LAG HD, Krapcho M, Mariotto A, Miller BA, Feuer EJ, Clegg L, et al. eds. SEER Cancer Statistics Review, 1975-2003, National Cancer Institute. Bethesda, MD, USA, based on November 2005 SEER data submission, posted to the SEER web site, 2006.
7. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982;51:189-99.
8. Jaffe ES HN, Stein H, Vardiman JW, editors. World Health Organization Classification of Tumours: pathology and genetics of tumours of haematopoietic and lymphoid tissues. IARC Press; 2001.
9. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002;100:2292-302.
10. Greenberg P, Anderson J, de Witte T, Estey E, Fenaux P, Gupta P, et al. Problematic WHO reclassification of myelodysplastic syndromes. Members of the International MDS Study Group. J Clin Oncol 2000;18:3447-52.
11. Germing U, Gattermann N. Refractory anemia with excess of blasts in transformation: a dying category? Leuk Res 2001;25:1095-6.
12. Strupp C, Gattermann N, Giagounidis A, Aul C, Hildebrandt B, Haas R, et al. Refractory anemia with excess of blasts in transformation: analysis of reclassification according to the WHO proposals. Leuk Res 2003;27:397-404.
13. Malcovati L, Porta MG, Pascutto C, Invernizzi R, Boni M, Travaglino E, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol 2005;23:7594-603.
14. Mufti GJ, Stevens JR, Oscier DG, Hamblin TJ, Machin D. Myelodysplastic syndromes: a scoring system with prognostic significance. Br J Haematol 1985;59:425-33.
15. Sanz GF, Sanz MA, Vallespi T, Canizo MC, Torrabadella M, Garcia S, et al. Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. Blood 1989;74:395-408.
16. Aul C, Gattermann N, Heyll A, Germing U, Derigs G, Schneider W. Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system. Leukemia 1992;6:52-9.
17. Morel P, Hebbar M, Lai JL, Duhamel A, Preudhomme C, Wattel E, et al. Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: a report on 408 cases. Leukemia 1993;7:1315-23.
18. Toyama K, Ohyashiki K, Yoshida Y, Abe T, Asano S, Hirai H, et al. Clinical implications of chromosomal abnormalities in 401 patients with myelodysplastic syndromes: a multicentric study in Japan. Leukemia 1993;7:499-508.
19. Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003;21:4642-9.
20. Head DR. Revised classification of acute myeloid leukemia. Leukemia 1996;10:1826-31.
21. Heim S, Mitelman F. Cytogenetic analysis in the diagnosis of acute leukemia. Cancer 1992;70 (Suppl 6):1701-9.
22. Moorman AV, Roman E, Willett EV, Dovey GJ, Cartwright RA, Morgan GJ. Karyotype and age in acute myeloid leukemia. Are they linked? Cancer Genet Cytogenet 2001;126:155-61.
23. Bloomfield CD, Lawrence D, Byrd JC, Carroll A, Pettenati MJ, Tantravahi R, et al. Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. Cancer Res 1998;58:4173-9.
24. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, 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;92:2322-33.
25. Sanderson RN, Johnson PR, Moorman AV, Roman E, Willett E, Taylor PR, et al. Population-based demographic study of karyotypes in 1709 patients with adult acute myeloid leukemia. Leukemia 2006;20:444-50.
26. Mauritzson N, Johansson B, Albin M, Billstrom R, Ahlgren T, Mikoczy Z, et al. A single-center population-based consecutive series or 1500 cytogenetically investigated adult hematological malignancies: karyotypic features in relation to morphology, age and gender. Eur J Haematol 1999;62:95-102.
27. Rossi G, Pelizzari AM, Bellotti D, Tonelli M, Barlati S. Cytogenetic analogy between myelodysplastic syndrome and acute myeloid leukemia of elderly patients. Leukemia 2000;14:636-41.
28. Keating MJ, Smith TL, Kantarjian H, Cork A, Walters R, Trujillo JM, et al. Cytogenetic pattern in acute myelogenous leukemia: a major reproducible determinant of outcome. Leukemia 1988;2:403-12.
29. Schiffer CA, Lee EJ, Tomiyasu T, Wiernik PH, Testa JR. Prognostic impact of cytogenetic abnormalities in patients with de novo acute nonlymphocytic leukemia. Blood 1989;73:263-70.
30. Wahlin A, Hornsten P, Jonsson H. Remission rate and survival in acute myeloid leukemia: impact of selection and chemotherapy. Eur J Haematol 1991;46:240-7.
31. Estey E, deLima M, Strom S, Pierce S, Freireich EJ, Keating MJ. Long-term follow-up of patients with newly diagnosed acute myeloid leukemia treated at the University of Texas M.D. Anderson Cancer Center. Cancer 1997;80 Suppl 11:2176-80.
32. Löwenberg B, Zittoun R, Kerkhofs H, Jehn U, Abels J, Debusscher L, et al. On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol 1989;7:1268-74.
33. Mengis C, Aebi S, Tobler A, Dahler W, Fey MF. Assessment of differences in patient populations selected for excluded from participation in clinical phase III acute myelogenous leukemia trials. J Clin Oncol 2003;21:3933-9.
34. Pulsoni A, Pagano L, Latagliata R, Casini M, Cerri R, Crugnola M, et al. Survival of elderly patients with acute myeloid leukemia. Haematologica 2004;89:296-302.
35. 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.
36. Rees JK, Gray RG, Wheatley K. Dose intensification in acute myeloid leukaemia: greater effectiveness at lower cost. Principal report of the Medical Research Council's AML9 study. MRC Leukaemia in Adults Working Party. Br J Haematol 1996;94:89-98.
37. Bishop JF, Lowenthal RM, Joshua D, Matthews JP, Todd D, Cobcroft R, et al. Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group. Blood 1990;75:27-32.
38. Dillman RO, Davis RB, Green MR, Weiss RB, Gottlieb AJ, Caplan S, et al. A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of Cancer and Leukemia Group B. Blood 1991;78:2520-6.
39. Büchner T, Hiddemann W, Schoch C, Haferlach T, Sauerland MC, Heinecke A. Acute myeloid leukaemia (AML): treatment of the older patient. Best Pract Res Clin Haematol 2001;14:139-51.
40. Hiddemann W, Kern W, Schoch C, Fonatsch C, Heinecke A, Wormann B, et al. Management of acute myeloid leukemia in elderly patients. J Clin Oncol 1999;1:3569-76.
41. Heinemann V, Jehn U. Acute myeloid leukemia in the elderly: biological features and search for adequate treatment. Ann Hematol 1991;63:179-88.
42. 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.
43. Gupta V, Chun K, Yi QL, Minden M, Schuh A, Wells R, et al. Disease biology rather than age is the most important determinant of survival of patients > or = 60 years with acute myeloid leukemia treated with uniform intensive therapy. Cancer 2005;103:2082-90.
44. Cutler CS, Lee SJ, Greenberg P, Deeg HJ, Perez WS, Anasetti C, et al. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood 2004;104:579-85.
45. de Lima M, Giralt, S. Allogeneic transplantation for the elderly patient with acute myelogeneous leukemia or myelodysplastic syndrome. Semin Hematol 2006;43:107-17.
46. Spyridonidis A, Kuttler T, Wäsch R, Samek E, Waterhouse M, Behringer D, et al. Reduced intensity conditioning compared to standard conditioning preserves the in vitro growth capacity of bone marrow stroma, which remains of host origin. Stem Cells Dev 2005;14:213-22.
47. Cahn JY, Labopin M, Mandelli F, Goldstone AH, Eberhardt K, Reiffers J, et al. Autologous bone marrow transplantation for first remission acute myeloblastic leukemia in patients older than 50 years: a retrospective analysis of the European Bone Marrow Transplant Group. Blood 1995;85:575-9.
48. Montillo M, Tedeschi A, Pagano L, Venditti A, Ferrara F, Fabris P, et al. Feasibility of peripheral blood stem cell rescue as intensification in elderly patients with acute myelocytic leukaemia: a pilot study from the Gimema Group. Gruppo Italiano Malattie Ematologiche Maligne Dell'Adulto. Br J Haematol 2000;111:334-7.
49. de la Rubia J, Saavedra S, Sanz GF, Martin G, Moscardo F, Martinez J, et al. Transplant-related mortality in patients older than 60 years undergoing autologous hematopoietic stem cell transplantation. Bone Marrow Transplant 2001;27:21-5.
50. Runde V, de Witte T, Arnold R, Gratwohl A, Hermans J, van Biezen A, et al. Bone marrow transplantation from HLA-identical siblings as first-line treatment in patients with myelodysplastic syndromes: early transplantation is associated with improved outcome. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 1998;21:255-61.
51. Du W, Dansey R, Abella EM, Baynes R, Peters WP, Klein J, et al. Successful allogeneic bone marrow transplantation in selected patients over 50 years of age-a single institution's experience. Bone Marrow Transplant 1998;21:1043-7.
52. Deeg HJ, Shulman HM, Anderson JE, Bryant EM, Gooley TA, Slattery JT, et al. Allogeneic and syngeneic marrow transplantation for myelodysplastic syndrome in patients 55 to 66 years of age. Blood 2000;95:1188-94.
53. McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001;97:3390-400.
54. Wong R, Giralt SA, Martin T, Couriel DR, Anagnostopoulos A, Hosing C, et al. Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years. Blood 2003;102:3052-9.
55. Bertz H, Potthoff K, Finke J. Allogeneic stem-cell transplantation from related and unrelated donors in older patients with myeloid leukemia. J Clin Oncol 2003;21:1480-4.
56. Bross PF, Beitz J, Chen G, Chen XH, Duffy E, Kieffer L, et al. Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin Cancer Res 2001;7:1490-6.
57. Kindler T, Breitenbuecher F, Marx A, Beck J, Hess G, Weinkauf B, et al. Efficacy and safety of imatinib in adult patients with c-kit-positive acute myeloid leukemia. Blood 2004;103:3644-54.
58. Lübbert M. DNA methylation inhibitors in the treatment of leukemias, myelodysplastic syndromes and hemoglobinopathies: clinical results and possible mechanisms of action. Curr Top Microbiol Immunol 2000;249:135-64.
59. Rüter B, Wijermans PW, Lübbert M. DNA methylation as a therapeutic target in hematologic disorders: recent results in older patients with myelodysplasia and acute myeloid leukemia. Int J Hematol 2004;80:128-35.
60. Greenberg PL, Lee SJ, Advani R, Tallman MS, Sikic BI, Letendre L, et al. Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995). J Clin Oncol 2004;22:1078-86.
61. Karp JE, Lancet JE, Kaufmann SH, End DW, Wright JJ, Bol K, et al. Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical-laboratory correlative trial. Blood 2001;97:3361-9.
62. Kosugi H, Towatari M, Hatano S, Kitamura K, Kiyoi H, Kinoshita T, et al. Histone deacetylase inhibitors are the potent inducer/enhancer of differentiation in acute myeloid leukemia: a new approach to anti-leukemia therapy. Leukemia 1999;13:1316-24.
63. Yu C, Rahmani M, Dent P, Grant S. The hierarchical relationship between MAPK signaling and ROS generation in human leukemia cells undergoing apoptosis in response to the proteasome inhibitor Bortezomib. Exp Cell Res 2004;295:555-66.
64. Fiedler W, Mesters R, Tinnefeld H, Loges S, Staib P, Duhrsen U, et al. A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia. Blood 2003;102:2763-7.
65. Stirewalt DL, Radich JP. The role of FLT3 in haematopoietic malignancies. Nat Rev Cancer 2003;3:650-65.
66. Marcucci G, Byrd JC, Dai G, Klisovic MI, Kourlas PJ, Young DC, et al. Phase 1 and pharmacodynamic studies of G3139, a Bcl-2 antisense oligonucleotide, in combination with chemotherapy in refractory or relapsed acute leukemia. Blood 2003;101:425-32.
67. Wijermans PW, Lübbert M, Verhoef G, Klimek V, Bosly A. An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2′-deoxycytidine (decitabine) in 177 patients. Ann Hematol 2005;84 Suppl 13:9-17.
68. Rüter B, Wijermans PW, Lübbert M. Superiority of prolonged low-dose azanucleoside administration? Results of 5-aza-2′-deoxycytidine retreatment in high-risk myelodysplasia patients. Cancer 2006;106:1744-50.
69. Tallman MS, Gilliland DG, Rowe JM. Drug therapy for acute myeloid leukemia. Blood 2005;106:1154-63.
70. Neuss MN, Feussner JR, DeLong ER, Cohen HJ. A quantitative analysis of palliative care decisions in acute nonlymphocytic leukemia. J Am Geriatr Soc 1987;35:125-31.
71. Chen H, Cantor A, Meyer J, Beth Corcoran M, Grendys E, Cavanaugh D, et al. Can older cancer patients tolerate chemotherapy? A prospective pilot study. Cancer 2003;97:1107-14.
72. Bokemeyer C, Kolb G. Geriatric oncology: appropriate assessment is the basis for clinical trials and routine care. Onkologie 2003;26:323-4.
73. Friedrich C, Kolb G, Wedding U, Pientka L. Comprehensive geriatric assessment in the elderly cancer patient. Onkologie 2003;26:355-60.
74. Balducci L, Yates J. General guidelines for the management of older patients with cancer. Oncology (Williston Park) 2000;14:221-7.
75. Sorror ML, Maris MB, Sandmaier BM, Storer BE, Stuart MJ, Hegenbart U, et al. Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. J Clin Oncol 2005;23:3819-29.
76. Pitako JA, Haas PS, Van den Bosch J, Müller-Berndorff H, Kündgen A, Germing U, et al. Quantification of outpatient management and hospitalization of patients with high-risk myelodysplastic syndrome treated with low-dose decitabine. Ann Hematol 2005;84 Suppl 13:25-31.
77. nd, Silverman LR, Demakos EP, Odchimar-Reissig R, Holland JF, 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;20:2441-52.
78. Kantarjian H, Issa JP, Rosenfeld CS, Bennett JM, Albitar M, Dipersio J, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 2006;106:1794-803.
79. Schumacher A, Wewers D, Heinecke A, Sauerland C, Koch OM, van de Loo J, et al. Fatigue as an important aspect of quality of life in patients with acute myeloid leukemia. Leuk Res 2002;26:355-62.
80. Miller KB, Kim K, Morrison FS, Winter JN, Bennett JM, Neiman RS, et al. The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study. Ann Hematol 1992;65:162-8.
81. Gerhartz HH, Marcus R, Delmer A, Zwierzina H, Suciu S, Dardenne M, et al. A randomized phase II study of low-dose cytosine arabinoside (LD-AraC) plus granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in myelodysplastic syndromes (MDS) with a high risk of developing leukemia. EORTC Leukemia Cooperative Group. Leukemia 1994;8:16-23.
82. Hornsten P, Wahlin A, Rudolphi O, Nordenson I. Myelodysplastic syndromes: a population-based study on transformation and survival. Acta Oncol 1995;34:473-8.
83. Hellstrom-Lindberg E, Ahlgren T, Beguin Y, Carlsson M, Carneskog J, Dahl IM, et al. Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients. Blood 1998;92:68-75.
84. Beran M, Shen Y, Kantarjian H, O'Brien S, Koller CA, Giles FJ, et al. High-dose chemotherapy in high-risk myelodysplastic syndrome: covariate-adjusted comparison of five regimens. Cancer 2001;92:1999-2015.
85. de Witte T, Suciu S, Verhoef G, Labar B, Archimbaud E, Aul C, et al. Intensive chemotherapy followed by allogeneic or autologous stem cell transplantation for patients with myelodysplastic syndromes (MDSs) and acute myeloid leukemia following MDS. Blood 2001;98:2326-31.
86. Silverman LR, Demakos EP, Peterson BL, Komblith AB, Holland JC, Odchimar-Reissig R, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 2002;20:2429-40.
87. Zwierzina H, Suciu S, Loeffler-Ragg J, Neuwirtova R, Fenaux P, Beksac M, et al. Low-dose cytosine arabinoside (LD-AraC) vs LD-AraC plus granulocyte/macrophage colony stimulating factor vs LD-AraC plus interleukin-3 for myelodysplastic syndrome patients with a high risk of developing acute leukemia: final results of a randomized phase III study (06903) of the EORTC Leukemia Cooperative Group. Leukemia 2005;19:1929-33.
88. Preiss BS, Kerndrup GB, Schmidt KG, Sorensen AG, Clausen NA, Gadeberg OV, et al. Cytogenetic findings in adult de novo acute myeloid leukaemia. A population-based study of 303/337 patients. Br J Haematol 2003;123:219-34.
89. Taylor PR, Reid MM, Stark AN, Bown N, Hamilton PJ, Proctor SJ. De novo acute myeloid leukaemia in patients over 55-years-old: a population-based study of incidence, treatment and outcome. Northern Region Haematology Group. Leukemia 1995;9:231-7.
90. Bauduer F, Ducout L, Dastugue N, Capdupuy C, Renoux M. De novo and secondary acute myeloid leukemia in patients over the age of 65: a review of fifty-six successive and unselected cases from a general hospital. Leuk Lymphoma 1999;35:289-96.
91. 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.
92. Sebban C, Archimbaud E, Coiffier B, Guyotat D, Treille-Ritouet D, Maupas J, et al. Treatment of acute myeloid leukemia in elderly patients. A retrospective study. Cancer 1988;61:227-31.
93. Orlandi E, Lazzarino M, Morra E, Castagnola C, Alessandrino EP, Bernasconi P, et al. Impact of advanced age on the management of acute nonlymphocytic leukemia: a study of 103 patients. Acta Haematol 1990;84:144-8.
94. Bassan R, Buelli M, Viero P, Minotti C, Barbui T. The management of acute myelogenous leukemia in the elderly: ten-year experience in 118 patients. Hematol Oncol 1992;10:251-60.
95. Baudard M, Marie JP, Cadiou M, Viguie F, Zittoun R. Acute myelogenous leukaemia in the elderly: retrospective study of 235 consecutive patients. Br J Haematol 1994;86:82-91.
96. Ferrara F, Annunziata M, Copia C, Magrin S, Mele G, Mirto S. Therapeutic options and treatment results for patients over 75 years of age with acute myeloid leukemia. Haematologica 1998;83:126-31.
97. Baudard M, Beauchamp-Nicoud A, Delmer A, Rio B, Blanc C, Zittoun R, et al. Has the prognosis of adult patients with acute myeloid leukemia improved over years? A single institution experience of 784 consecutive patients over a 16-year period. Leukemia 1999;13:1481-90.
98. Spataro V, Kovacsovics T, Bach S, Pampallona S, Schapira M, Cavalli F. Acute myeloid leukemia in the elderly: results of an individualized approach in two centres. Leuk Lymphoma 2000;39:521-30.
99. Lopez A, de la Rubia J, Martin G, Martinez J, Cervera J, Jarque I, et al. Recent improvements in outcome for elderly patients with de novo acute myeloblastic leukemia. Leuk Res 2001;25:685-92.
100. Yoshida S, Kuriyama K, Miyazaki Y, Taguchi J, Fukushima T, Honda M, et al. De novo acute myeloid leukemia in the elderly; a consistent fraction of long-term survivors by standard-dose chemotherapy. Leuk Res 2001;25:33-8.
101. Behringer B, Pitako JA, Kunzmann R, Schmoor C, Behringer D, Mertelsmann R, et al. Prognosis of older patients with acute myeloid leukemia receiving either induction or noncurative treatment: a single-center retrospective study. Ann Hematol 2003;82:381-9.
102. Vey N, Coso D, Bardou VJ, Stoppa AM, Braud AC, Bouabdallah R, et al. The benefit of induction chemotherapy in patients age > or = 75 years. Cancer 2004;101:325-31.
103. Kahn SB, Begg CB, Mazza JJ, Bennett JM, Bonner H, Glick JH. Full dose versus attenuated dose daunorubicin, cytosine arabinoside, and 6-thioguanine in the treatment of acute nonlymphocytic leukemia in the elderly. J Clin Oncol 1984;2:865-70.
104. Liu Yin JA, Johnson PR, Davies JM, Flanagan NG, Gorst DW, Lewis MJ. Mitozantrone and cytosine arabinoside as first-line therapy in elderly patients with acute myeloid leukaemia. Br J Haematol 1991;79:415-20.
105. Wiernik PH, Banks PL, Case DC, Jr., Arlin ZA, Periman PO, Todd MB, et al. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood 1992;79:313-9.
106. Ruutu T, Almqvist A, Hallman H, Honkanen T, Jarvenpaa E, Jarventie G, et al. Oral induction and consolidation of acute myeloid leukemia with etoposide, 6-thioguanine, and idarubicin (ETI) in elderly patients: a randomized comparison with 5-day TAD. Finnish Leukemia Group. Leukemia 1994;8:11-5.
107. Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med 1994;331:896-903.
108. Reiffers J, Huguet F, Stoppa AM, Molina L, Marit G, Attal M, et al. A prospective randomized trial of idarubicin vs daunorubicin in combination chemotherapy for acute myelogenous leukemia of the age group 55 to 75. Leukemia 1996;10:389-95.
109. Archimbaud E, Jehn U, Thomas X, De Cataldo F, Fillet G, Belhabri A, et al. Multicenter randomized phase II trial of idarubicin vs mitoxantrone, combined with VP-16 and cytarabine for induction/consolidation therapy, followed by a feasibility study of autologous peripheral blood stem cell transplantation in elderly patients with acute myeloid leukemia. Leukemia 1999;13:843-9.
110. Löwenberg 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.
111. Bouabdallah R, Lefrere F, Rose C, Chaibi P, Harousseau JL, Vernant JP, et al. A phase II trial of induction and consolidation therapy of acute myeloid leukemia with weekly oral idarubicin alone in poor risk elderly patients. Leukemia 1999;13:1491-6.
112. 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.
113. 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.
114. Dalley CD, Lillington DL, Bradburn M, Carter M, Amess JA, Rohatiner AZ, et al. Acute myelogenous leukaemia in older patients at St Bartholomew's Hospital: outcome with mitoxantrone and cytarabine. Hematol J 2002;3:237-43.
115. 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.
116. Öberg G, Killander A, Bjoreman M, Gahrton G, Grimfors G, Gruber A, et al. Long-term follow-up of patients >or=60 yr old with acute myeloid leukaemia treated with intensive chemotherapy. Eur J Haematol 2002;68:376-81.
117. Haferlach T, Schoch C, Loffler H, Gassmann W, Kern W, Schnittger S, et al. Morphologic dysplasia in de novo acute myeloid leukemia (AML) is related to unfavorable cytogenetics but has no independent prognostic relevance under the conditions of intensive induction therapy: results of a multiparameter analysis from the German AML Co-operative Group studies. J Clin Oncol 2003;21:256-65.
118. Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, 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 Co-operative Oncology Group. Blood 2004;103:479-85.
119. Schlenk RF, Fröhling 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.
120. Büchner T, Berdel WE, Schoch C, Haferlach T, Serve HL, Kienast J, et al. Double induction containing either two courses or one course of high-dose cytarabine plus mitoxantrone and postremission therapy by either autologous stem-cell transplantation or by prolonged maintenance for acute myeloid leukemia. J Clin Oncol 2006;24:2480-9.