Acute myeloid leukaemia: Optimal management and recent developments

Drugs

Volumn 71, Issue 12, 2011, Pages 1537-1550

  Villela, Luis ^a   Bolaños Meade, Javier ^b  

^a HOSPITAL ZAMBRANO HELLION   (Mexico)

^b JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

Alvocidib; Anthracyclines; Azacitidine; Clofarabine; Daunorubicin; Decitabine; Gemtuzumab ozogamicin; Idarubicin; Lestaurtinib; Lintuzumab; Midostaurin; Myeloid leukaemia; Sorafenib; Tipifarnib.

Indexed keywords

AZACITIDINE; BIOLOGICAL MARKER; CLOFARABINE; CYTARABINE; DAUNORUBICIN; ETOPOSIDE; FLAVOPIRIDOL; GEMTUZUMAB OZOGAMICIN; HYDRALAZINE; IDARUBICIN; LESTAURTINIB; LINTUZUMAB; MAMMALIAN TARGET OF RAPAMYCIN; MIDOSTAURIN; MITOXANTRONE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SORAFENIB; TIOGUANINE; TIPIFARNIB; VALPROIC ACID;

ACUTE GRANULOCYTIC LEUKEMIA; CANCER COMBINATION CHEMOTHERAPY; CANCER SURVIVAL; CLINICAL TRIAL; CLINICAL TRIAL (TOPIC); CONTINUOUS INFUSION; DRUG DOSE INCREASE; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; DRUG RESPONSE; DRUG TOLERABILITY; EPIGENETICS; HUMAN; LOW DRUG DOSE; REVIEW; SINUSOIAL OBSTRUCTIVE SYNDROME; STEM CELL TRANSPLANTATION; VEIN OCCLUSION;

ADENINE NUCLEOTIDES; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; ARABINONUCLEOSIDES; DAUNORUBICIN; FLAVONOIDS; HUMANS; LEUKEMIA, MYELOID, ACUTE; PIPERIDINES;

EID: 80051976690     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: 10.2165/11593060-000000000-00000     Document Type: Review

References (121)

1. Lö wenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N Engl J Med 1999; 341 (14): 1051-62 (Pubitemid 29451802)
2. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009; 114 (5): 937-51
3. 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
4. Surveillance Research Program, National Cancer Institute. Fast Stats: an interactive tool for access to SEER cancer statistics [online]. Available from URL: http://seer.cancer. gov/faststats [Accessed 2010 Dec 20]
5. Altekruse SF, Kosary CL, KrapchoM, et al. SEER cancer statistics review, 1975-2007. Bethesda (MD): National Cancer Institute, 2007
6. Villela L, Bolañ os-Meade J. Blood and bone marrow transplantation for acute myeloid leukemia. Clin Leuk 2009; 2: E11-21
7. Swirsky DM, de Bastos M, Parish SE, et al. Features affecting outcome during remission induction of acute myeloid leukaemia in 619 adult patients. Br J Haematol 1986; 64: 435-53 (Pubitemid 17184254)
8. Bolañ os-Meade J, Guo C, Gojo I, et al. A phase II study of timed sequential therapy of acute myelogenous leukemia (AML) for patients over the age of 60: two cycle timed sequential therapy with topotecan, ara-C andmitoxantrone in adults with poor-risk AML. Leuk Res 2004; 28: 571-7 (Pubitemid 38543194)
9. Castaigne S, Chevret S, Archimbaud E, et al. Randomized comparison of double induction and timed-sequential induction to a '3 + 7' induction in adults with AML: longterm analysis of the Acute Leukemia French Association (ALFA) 9000 study. Blood 2004; 104: 2467-74 (Pubitemid 39331849)
10. Bolañ os-Meade J, Karp JE, Guo CF, et al. Timed sequential therapy of acute myelogenous leukemia in adults: a phase II study of retinoids in combination with the sequential administration of cytosine arabinoside, idarubicin and etoposide. Leuk Res 2003; 27: 313-21 (Pubitemid 36071388)
11. 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: 2322-33 (Pubitemid 28452973)
12. 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: 4325-36 (Pubitemid 35429670)
13. Marcucci G, Mrozek K, Ruppert AS, et al. Abnormal cytogenetics at date of morphologic complete remission predicts short overall and disease-free survival, and higher relapse rate in adult acute myeloid leukemia: results from cancer and leukemia group B study 8461. J Clin Oncol 2004; 22: 2410-8 (Pubitemid 41115398)
14. Kottaridis PD, Gale RE, Frew ME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 2001; 98: 1752-9
15. 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 (Pubitemid 35177429)
16. Thiede C, Steudel C, Mohr B, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 2002; 99: 4326-35 (Pubitemid 34627197)
17. Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 2005; 352: 254-66 (Pubitemid 40110814)
18. Boissel N, Renneville A, Biggio V, et al. Prevalence, clinical profile, and prognosis of NPM mutations in AML with normal karyotype. Blood 2005; 106: 3618-20 (Pubitemid 41609201)
19. Thiede C,Koch S, Creutzig E, et al. Prevalence and prognostic impact ofNPM1mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood 2006; 107: 4011-20 (Pubitemid 43726809)
20. Gale RE, Green C, Allen C, et al. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood 2008; 111: 2776-84
21. 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: 453-74
22. Arber DA, Brunning RD, Le Beau MM, et al. Acute myeloid leukaemia with recurrent genetic abnormalities. In: Swerdlow SH, Campo E, Harris NL, et al. editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: International Agency for Research on Cancer (IARC), 2008: 110-23
23. Schnittger S, Schoch C, Kern W, et al. Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood 2005; 106: 3733-9 (Pubitemid 41739006)
24. Falini B, Macijewski K, Weiss T, et al. Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features of AML with mutated nucleophosmin (NPM1). Blood 2010; 115: 3776-85
25. Díaz-Beyá M, Rozman M, Pratcorona M, et al. The prognostic value of multilineage dysplasia in de novo acute myeloid leukemia patients with intermediate-risk cytogenetics is dependent on NPM1 mutational status. Blood 2010; 116: 6147-8
26. Falini B, Martelli MP, Bolli N, et al. Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity? Blood 2011; 117 (4): 1109-20
27. Zhang P, Iwasaki-Arai J, Iwasaki H, et al. Enhancement of hematopoietic stem cell repopulating capacity and selfrenewal in the absence of the transcription factor C/EBP alpha. Immunity 2004; 21: 853-63 (Pubitemid 39642186)
28. Rosenbauer F, Tenen DG. Transcription factors in myeloid development: balancing differentiation with transformation. Nat Rev Immunol 2007; 7: 105-17 (Pubitemid 46174858)
29. Frö hling S, Schlenk RF, Stolze I, et al. CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations. J Clin Oncol 2004 15; 22: 624-33 (Pubitemid 41095065)
30. Taskesen E, Bullinger L, Corbacioglu A. Prognostic impact, concurrent genetic mutations and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML: further evidence for CEBPA double mutant AML as a distinctive disease entity. Blood 2011; 117 (8): 2469-75
31. Nakao M, Yokota S, Iwai T, et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia 1996; 10: 1911-8 (Pubitemid 27019637)
32. Small D. FLT3 mutations: biology and treatment. Hematology Am Soc Hematol Educ Program 2006; 178-84
33. Stirewalt DL, Radich JP. The role of FLT3 in haematopoietic malignancies. Nat Rev Cancer 2003; 3: 650-65 (Pubitemid 37328820)
34. Rai KR, Holland JF, Glidewell OJ, et al. Treatment of acute myelocytic leukemia: a study by cancer and leukemia group B. Blood 1981; 58: 1203-12 (Pubitemid 12251149)
35. Dillman RO, Davis RB, Green MR, 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
36. Wahlin A, Hö rnsten P, Hedenus M, et al. Mitoxantrone and cytarabine versus daunorubicin and cytarabine in previously untreated patients with acute myeloid leukemia. Cancer Chemother Pharmacol 1991; 28: 480-3
37. Archimbaud E, Jehn U, Thomas X, 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 (Pubitemid 29292132)
38. Lö wenberg 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 acutemyeloid leukemia in the elderly: final report. European Organization for theResearch and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group. J ClinOncol 1998 Mar; 16: 872-81 (Pubitemid 28115455)
39. Flasshove M, Meusers P, Schü tte J, et al. Long-term survival after induction therapy with idarubicin and cytosine arabinoside for de novo acute myeloid leukemia. Ann Hematol 2000; 79: 533-42
40. Bü chner T, Hiddemann W, Wö rmann B, et al. Double induction strategy for acute myeloid leukemia: the effect of high-dose cytarabine with mitoxantrone instead of standard-dose cytarabine with daunorubicin and 6-thioguanine: a randomized trial by the German AML Cooperative Group. Blood 1999; 93: 4116-24 (Pubitemid 29279253)
41. The AML cooperative group. A systematic collaborative overview of randomized trials comparing idarubicin with daunorubicin (or other anthracyclines) as induction therapy for acute myeloid leukaemia. AML Collaborative Group. Br J Haematol 1998; 103: 100-9
42. Kimby E, Nygren P, Glimelius B. SBU-group. Swedish Council of Technology Assessment in Health Care. A systematic overview of chemotherapy effects in acute myeloid leukaemia. Acta Oncol 2001; 40: 231-52 (Pubitemid 32590834)
43. Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med 2009; 361: 1249-59
44. Lö wenberg B, Ossenkoppele GJ, van Putten W, et al. Highdose daunorubicin in older patients with acute myeloid leukemia [published erratum appears in N Engl J Med 2010; 362 (12): 1155]. N Engl J Med 2009; 361: 1235-48
45. Mandelli F, Vignetti M, Suciu S, et al. Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10 [published erratum appears in J Clin Oncol 2010; 28: 1438]. J Clin Oncol 2009; 27: 5397-403
46. Masquelier M, Vitols S. Drastic effect of cell density on the cytotoxicity of daunorubicin and cytosine arabinoside. Biochem Pharmacol 2004; 67: 1639-46 (Pubitemid 38479842)
47. Bogason A, Quartino AL, Lafolie P, et al. Inverse relationship between leukemic cell burden and plasma levels of daunorubicin in patients with acute myeloid leukemia. Br J Clin Pharmacol 2011; 71 (4): 514-21
48. Gupta V, Tallman M, Weisdorf DJ. Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns. Blood 2011; 117 (8): 2307-18
49. Becker H,Marcucci G, MaharryK, 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 LeukemiaGroup B study. J Clin Oncol 2010; 28: 596-604
50. Bü chner T, Hiddemann W, Berdel WE, 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 (Pubitemid 46603514)
51. Szotkowski T, Muzik J, Voglova J, et al. Prognostic factors and treatment outcome in 1,516 adult patients with de novo and secondary acute myeloid leukemia in 1999-2009 in 5 hematology intensive care centers in the Czech Republic. Neoplasma 2010; 57: 578-89
52. Abou-Jawde RM, Sobecks R, Pohlman B, et al. The role of post-remission chemotherapy for older patients with acute myelogenous leukemia. Leuk Lymphoma 2006; 47: 689-95
53. 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 Nov 25; 116: 4422-9
54. Pigneux A, Harousseau JL, Witz F, et al. Addition of lomustine to idarubicin and cytarabine improves the outcome of elderly patients with de novo acute myeloid leukemia: a report from the GOELAMS. J Clin Oncol 2010 Jun 20; 28: 3028-34
55. Kanemura N, Tsurumi H, Kasahara S, et al. Continuous drip infusion of low dose cytarabine and etoposide with granulocyte colony-stimulating factor for elderly patients with acute myeloid leukaemia ineligible for intensive chemotherapy. Hematol Oncol 2008 Mar; 26: 33-8 (Pubitemid 351448909)
56. Yamauchi T, Negoro E, Arai H, et al. Combined low-dose cytarabine, melphalan and mitoxantrone for older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. Anticancer Res 2007 Jul-Aug; 27: 2635-9 (Pubitemid 47227976)
57. Whitman SP, Maharry K, Radmacher MD, et al. FLT3 internal tandem duplication associates with adverse outcome and gene-and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood 2010; 116: 3622-6
58. Breccia M, Frustaci AM, Cannella L, et al. Comorbidities and FLT3-ITD abnormalities as independent prognostic indicators of survival in elderly acute myeloid leukaemia patients. Hematol Oncol 2009; 27: 148-53
59. Roboz GJ, Knovich MA, Bayer RL, et al. Efficacy and safety of gemtuzumab ozogamicin in patients with poorprognosis acute myeloid leukemia. Leuk Lymphoma 2002; 43: 1951-5
60. Leopold LH, Berger MS, Cheng SC, et al. Comparative efficacy and safety of gemtuzumab ozogamicin monotherapy and high-dose cytarabine combination therapy in patients with acute myeloid leukemia in first relapse. Clin Adv Hematol Oncol 2003; 1: 220-5
61. Cortes J, Tsimberidou AM, Alvarez R, et al. Mylotarg combined with topotecan and cytarabine in patients with refractory acute myelogenous leukemia. Cancer Chemother Pharmacol 2002; 50: 497-500 (Pubitemid 35435529)
62. Apostolidou E, Cortes J, Tsimberidou A, et al. Pilot study of gemtuzumab ozogamicin, liposomal daunorubicin, cytarabine and cyclosporine regimen in patients with refractory acute myelogenous leukemia. Leuk Res 2003; 27: 887-91 (Pubitemid 36809083)
63. Chevallier P, Roland V, Mahé B, et al. Administration of mylotarg 4 days after beginning of a chemotherapy including intermediate-dose aracytin and mitoxantrone (MIDAM regimen) produces a high rate of complete hematologic remission in patients with CD33+ primary resistant or relapsed acute myeloid leukemia. Leuk Res 2005; 29: 1003-7 (Pubitemid 40982594)
64. Martin MG, Augustin KM, Uy GL, et al. Salvage therapy for acute myeloid leukemia with fludarabine, cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G-CSF. Am J Hematol 2009; 84: 733-7
65. Larson RA, Sievers EL, Stadtmauer EA. 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: 1442-52 (Pubitemid 41356159)
66. McKoy JM, Angelotta C, Bennett CL, et al. Gemtuzumab ozogamicin- associated sinusoidal obstructive syndrome (SOS): an overview from the Research on Adverse Drug Events and Reports (RADAR) project. Leuk Res 2007; 31: 599-604 (Pubitemid 46578145)
67. Amadori S, Suciu S, Selleslag D, et al. Randomized trial of two schedules of low-dose gemtuzumab ozogamicin as induction monotherapy for newly diagnosed acute myeloid leukaemia in older patients not considered candidates for intensive chemotherapy: a phase II study of the EORTC and GIMEMA leukaemia groups (AML-19). Br J Haematol 2010; 149 (3): 376-82
68. McHayleh W, Foon K, Redner R, et al. Gemtuzumab ozogamicin as first-line treatment in patients aged 70 years or older with acute myeloid leukemia. Cancer 2010; 116: 3001-5
69. Candoni A, Martinelli G, Toffoletti E, et al. Gemtuzumabozogamicin in combination with fludarabine, cytarabine, idarubicin (FLAI-GO) as induction therapy in CD33-positive AML patients younger than 65 years. Leuk Res 2008; 32: 1800-8
70. Amadori S, Suciu S, Willemze R, et al. Sequential administration of gemtuzumab ozogamicin and conventional chemotherapy as first line therapy in elderly patients with acute myeloid leukemia: a phase II study (AML-15) of the EORTC and GIMEMA leukemia groups.Haematologica 2004; 89: 950-6 (Pubitemid 39049903)
71. Eom KS, Kim HJ, MinWS, et al. Gemtuzumab ozogamicin in combination with attenuated doses of standard induction chemotherapy can successfully induce complete remission without increasing toxicity in patients with acute myeloid leukemia aged 55 or older. Eur JHaematol 2007; 79: 398-404
72. Burnett AK, Hills RK, Milligan D, et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol 2011; 29 (4): 369-77
73. US FDA. Mylotarg (gemtuzumab ozogamicin): market withdrawal [online]. Available from URL: http://www.fda.gov/Safety/MedWatch/SafetyInformation/Safety AlertsforHumanMedicalProducts/ucm216458.htm [Accessed 2011 Jul 21]
74. Scheinberg DA, Tanimoto M, McKenzie S, et al. Monoclonal antibody M195: a diagnostic marker for acute myelogenous leukemia. Leukemia 1989; 3: 440-5 (Pubitemid 19145303)
75. Meloni G, Foa R, Vignett M, et al. Interleukin 2 may induce prolonged remissions in advanced acute myelogenous leukemia. Blood 1994; 84: 2158-63 (Pubitemid 24296372)
76. Feldman EJ, Brandwein J, Stone R, et al. Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia. J Clin Oncol 2005; 23: 4110-6 (Pubitemid 46211316)
77. Chapuis N, Park S, Leotoing L, et al. IkB kinase overcomes PI3K/Akt and ERK/MAPK to control FOXO3a activity in acute myeloid leukemia. Blood 2010; 116: 4240-50
78. Zebisch A, Czernilofsky AP, Keri G, et al. Signaling through RAS-RAF-MEK-ERK: from basics to bedside. Curr Med Chem 2007; 14: 601-23 (Pubitemid 46477731)
79. Lü bbert M, Oster W, Knopf HP, et al. N-RAS gene activation in acute myeloid leukemia: association with expression of interleukin-6. Leukemia 1993; 7: 1948-54 (Pubitemid 24003211)
80. Récher C, Beyne-Rauzy O, Demur C, et al. Antileukemic activity of rapamycin in acute myeloid leukemia. Blood 2005; 105: 2527-34 (Pubitemid 40387055)
81. Lee J, Hwang J, Kim HS, et al. A comparison of gene expression profiles between primary human AML cells and AML cell line. Genes Genet Syst 2008; 83: 339-45
82. Karp JE, Lancet JE, Kaufmann SH, 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
83. Harousseau JL, Lancet JE, Reiffers J, et al. A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib in patients with refractory or relapsed acute myeloid leukemia. Blood 2007; 109: 5151-6 (Pubitemid 46890529)
84. Lancet JE, Gojo I, Gotlib J, et al. A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia. Blood 2007; 109: 1387-94 (Pubitemid 46242109)
85. Harousseau JL, Martinelli G, Jedrzejczak WW, et al. A randomized phase 3 study of tipifarnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older. Blood 2009; 114: 1166-73
86. 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: 4841-52
87. Karp JE, Smith BD, Gojo I, et al. Phase II trial of tipifarnib as maintenance therapy in first complete remission in adults with acute myelogenous leukemia and poor-risk features. Clin Cancer Res 2008; 14: 3077-82
88. Crump M, Hedley D, Kamel-Reid S, et al. A randomized phase I clinical and biologic study of two schedules of sorafenib in patients with myelodysplastic syndrome or acute myeloid leukemia: a NCIC (National Cancer Institute of Canada) Clinical Trials Group Study. Leuk Lymphoma 2010; 51: 252-60
89. Metzelder S, Wang Y, Wollmer E, et al. Compassionate use of sorafenib in Flt3-ITD positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation. Blood 2009; 113: 6567-71
90. Ravandi F, Cortes JE, Jones D, et al. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol 2010; 28: 1856-62
91. Fischer T, Stone RM, Deangelo DJ. Phase IIB trial of oral midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol 2010; 28: 4339-45
92. Knapper S, Burnett AK, Littlewood T, et al. A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. Blood 2006; 108: 3262-70
93. End DW, Smets G, Todd AV, et al. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res 2001; 61: 131-7 (Pubitemid 32095710)
94. Hotte SJ, Hirte HW. BAY 43-9006: early clinical data in patients with advanced solid malignancies. Curr Pharm Des 2002; 8: 2249-53 (Pubitemid 35189897)
95. ZhangW, Konopleva M, Ruvolo VR, et al. Sorafenib induces apoptosis of AML cells via Bim-mediated activation of the intrinsic apoptotic pathway. Leukemia 2008; 22: 808-18 (Pubitemid 351552630)
96. Knapper S, Mills KI, Gilkes AF, et al. The effects of lestaurtinib (CEP701) and PKC412 on primary AML blasts: the induction of cytotoxicity varies with dependence on FLT3 signaling in both FLT3-mutated and wild-type cases. Blood 2006; 108: 3494-503
97. Cancer and Leukemia Group B.Daunorubicin, cytarabine, and midostaurin in treating patients with newly diagnosed acute myeloid leukemia [ClinicalTrials.gov identifier NCT00651261]. US National Institutes of Health, ClinicalTrials. gov [online]. Available from URL: http://www.clinicaltrial.gov [Accessed 2011 Apr 7]
98. Yang J, Ikezoe T,Nishioka C, et al. Inhibition of mTORC1 by RAD001 (everolimus) potentiates the effects of 1,25-dihydroxyvitamin D(3) to induce growth arrest and differentiation of AML cells in vitro and in vivo. Exp Hematol 2010; 38: 666-76
99. Janus A, Linke A, Cebula B, et al. Rapamycin, the mTOR kinase inhibitor, sensitizes acute myeloid leukemia cells, HL-60 cells, to the cytotoxic effect of arabinozide cytarabine. Anticancer Drugs 2009; 20: 693-701
100. Figueroa ME, Lugthart S, Li Y, et al. DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell 2010; 17: 13-27
101. Bullinger L, Ehrich M, Döhner K, et al. Quantitative DNA methylation predicts survival in adult acute myeloid leukemia. Blood 2010; 115: 636-42
102. Götze K, Platzbecker U, Giagounidis A, et al. Azacitidine for treatment of patients with myelodysplastic syndromes (MDS): practical recommendations of the German MDS Study Group. Ann Hematol 2010; 89: 841-50
103. Silverman LR, McKenzie DR, Peterson BL, et al. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol 2006; 24: 3895-903 (Pubitemid 46630737)
104. Buckstein R, Yee K,Wells RA. The Canadian Consortium on Evidence-based Care in MDS. 5-Azacytidine in myelodysplastic syndromes: a clinical practice guideline. Cancer Treat Rev 2011; 37 (2): 160-7
105. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 2009; 10: 223-32
106. Hollenbach PW, Nguyen AN, Brady H, et al. A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell lines. PLoS One 2010; 5 (2): e9001
107. Bolaños-Meade J, Smith BD, Gore SD, et al. 5-Azacytidine as salvage treatment in relapsed myeloid tumors after allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 2011; 17 (5): 754-8
108. Czibere A, Bruns I, Kröger N, et al. 5-Azacytidine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome who relapse after allo-SCT: a retrospective analysis. Bone Marrow Transplant 2010; 45: 872-6
109. Villela L, Anders V, Bolaños-Meade J. Predonor lymphocyte infusion treatment with 5-azacytidine as salvage treatment in relapsed acute myeloid leukaemia secondary to myelodysplastic syndrome. Anticancer Drugs 2010; 21: 469
110. Candelaria M, Herrera A, Labardini J, et al. Hydralazine and magnesium valproate as epigenetic treatment for myelodysplastic syndrome: preliminary results of a phase-II trial. Ann Hematol 2011; 90: 379-87
111. Decker RH, Dai Y, Grant S. The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in human leukemia cells (U937) through the mitochondrial rather than the receptor-mediated pathway. Cell DeathDiffer 2001; 8: 715-24 (Pubitemid 32685169)
112. Karp JE, Smith BD, Levis MJ, et al. Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk acute myelogenous leukemia. Clin Cancer Res 2007; 13: 4467-73 (Pubitemid 47219715)
113. Karp JE, Blackford A, Smith BD. Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia. Leuk Res 2010; 34: 877-82
114. Karp JE, Smith BD, Resar LS, et al. Phase I and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias. Blood 2011; 117 (12): 3302-10
115. Bonate PL, Arthaud L, Cantrell Jr WR, et al. Discovery and development of clofarabine: a nucleoside analogue for treating cancer. Nat Rev Drug Discov 2006; 5: 855-63 (Pubitemid 44480539)
116. Burnett AK, Russell NH, Kell J, et al. European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy. J Clin Oncol 2010; 28: 2389-95
117. Kantarjian HM, Erba HP, Claxton D, et al. Phase II study of clofarabine monotherapy in previously untreated older adults with acute myeloid leukemia and unfavorable prognostic factors. J Clin Oncol 2010; 28: 549-55
118. Ribeiro RC, Rego E. Management of APL in developing countries: epidemiology, challenges and opportunities for international collaboration. Hematology Am Soc Hematol Educ Program 2006: 162-8
119. Buitrón-Santiago N, Arteaga-Ortiz L, Rosas-López A, et al. Acute myeloid leukemia in adults: experience at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán from 2003 to 2008. Rev Invest Clin 2010; 62: 100-8
120. Ruiz-Argüelles GJ, Apreza-Molina MG, Alemán-Hoey DD, et al. Outpatient supportive therapy after induction to remission therapy in adult acute myelogenous leukaemia (AML) is feasible: a multicentre study. Eur J Haematol 1995; 54: 18-20
121. Pavlovsky S, Gonzalez Llaven J, Garcia Martinez MA, et al. A randomized study of mitoxantrone plus cytarabine versus daunomycin plus cytarabine in the treatment of previously untreated adult patients with acute nonlymphocytic leukemia. Ann Hematol 1994; 69: 11-5 (Pubitemid 24255442)