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Induction therapy for acute myeloid leukemia in younger adults

Author
Richard A Larson, MD
Section Editor
Bob Lowenberg, MD, PhD
Deputy Editor
Alan G Rosmarin, MD

INTRODUCTION

Once the diagnosis of acute myeloid leukemia (AML) is established, induction chemotherapy is given with the goal of rapidly restoring normal bone marrow function. Among patients with AML, treatment regimens and outcomes may differ between younger and older adults. Although there is no clear dividing line between younger and older adults when dealing with AML, in most studies, "older adults" has been defined as over age 55 to 60 years.

The initial treatment of younger adults with de novo AML will be reviewed here. The following exceptions, which require modification of standard treatment regimens, are discussed separately:

Treatment of older adults with AML (see "Treatment of acute myeloid leukemia in older adults")

Treatment of therapy-related AML (see "Therapy-related myeloid neoplasms: Acute myeloid leukemia and myelodysplastic syndrome")

Treatment of acute promyelocytic leukemia (FAB M3) (see "Initial treatment of acute promyelocytic leukemia in adults" and "Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults")

                                      

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Literature review current through: Nov 2016. | This topic last updated: Thu Aug 18 00:00:00 GMT+00:00 2016.
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References
Top
  1. Döhner 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.
  2. Williford SK, Salisbury PL 3rd, Peacock JE Jr, et al. The safety of dental extractions in patients with hematologic malignancies. J Clin Oncol 1989; 7:798.
  3. Bertoli S, Bérard 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; 121:2618.
  4. Sekeres MA, Elson P, Kalaycio ME, et al. Time from diagnosis to treatment initiation predicts survival in younger, but not older, acute myeloid leukemia patients. Blood 2009; 113:28.
  5. Atallah E, Cortes J, O'Brien S, et al. Establishment of baseline toxicity expectations with standard frontline chemotherapy in acute myelogenous leukemia. Blood 2007; 110:3547.
  6. 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. J Clin Oncol 2009; 27:5397.
  7. Löwenberg B, Ossenkoppele GJ, van Putten W, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med 2009; 361:1235.
  8. Teuffel O, Leibundgut K, Lehrnbecher T, et al. Anthracyclines during induction therapy in acute myeloid leukaemia: a systematic review and meta-analysis. Br J Haematol 2013; 161:192.
  9. 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; 103:479.
  10. Ohtake S, Miyawaki S, Fujita H, et al. Randomized study of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSG AML201 Study. Blood 2011; 117:2358.
  11. Li X, Xu S, Tan Y, Chen J. The effects of idarubicin versus other anthracyclines for induction therapy of patients with newly diagnosed leukaemia. Cochrane Database Syst Rev 2015; :CD010432.
  12. Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med 2009; 361:1249.
  13. Luskin MR, Lee JW, Fernandez HF, et al. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood 2016; 127:1551.
  14. Lee JH, Joo YD, Kim H, et al. A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia. Blood 2011; 118:3832.
  15. Kolitz JE, George SL, Marcucci G, et al. P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808. Blood 2010; 116:1413.
  16. Kolitz JE, George SL, Dodge RK, et al. Dose escalation studies of cytarabine, daunorubicin, and etoposide with and without multidrug resistance modulation with PSC-833 in untreated adults with acute myeloid leukemia younger than 60 years: final induction results of Cancer and Leukemia Group B Study 9621. J Clin Oncol 2004; 22:4290.
  17. Burnett AK, Russell NH, Hills RK, et al. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood 2015; 125:3878.
  18. Burnett AK, Russell NH, Hills RK, United Kingdom National Cancer Research Institute Acute Myeloid Leukemia Study Group. Higher daunorubicin exposure benefits FLT3 mutated acute myeloid leukemia. Blood 2016; 128:449.
  19. Arlin Z, Case DC Jr, Moore J, et al. Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Lederle Cooperative Group. Leukemia 1990; 4:177.
  20. MacCallum PK, Davis CL, Rohatiner AZ, et al. Mitoxantrone and cytosine arabinoside as treatment for acute myelogenous leukemia (AML) at first recurrence. Leukemia 1993; 7:1496.
  21. Büchner T, Hiddemann W, Wörmann 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.
  22. Ho AD, Lipp T, Ehninger G, et al. Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia--an active and well-tolerated regimen. J Clin Oncol 1988; 6:213.
  23. Feldman EJ, Alberts DS, Arlin Z, et al. Phase I clinical and pharmacokinetic evaluation of high-dose mitoxantrone in combination with cytarabine in patients with acute leukemia. J Clin Oncol 1993; 11:2002.
  24. Estey EH, Thall PF, Cortes JE, et al. Comparison of idarubicin + ara-C-, fludarabine + ara-C-, and topotecan + ara-C-based regimens in treatment of newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts in transformation, or refractory anemia with excess blasts. Blood 2001; 98:3575.
  25. Russo D, Malagola M, de Vivo A, et al. Multicentre phase III trial on fludarabine, cytarabine (Ara-C), and idarubicin versus idarubicin, Ara-C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients. Br J Haematol 2005; 131:172.
  26. Bishop JF, Lowenthal RM, Joshua D, et al. Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group. Blood 1990; 75:27.
  27. Hann IM, Stevens RF, Goldstone AH, et al. Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia. Results of the Medical Research Council's 10th AML trial (MRC AML10). Adult and Childhood Leukaemia Working Parties of the Medical Research Council. Blood 1997; 89:2311.
  28. Büchner T, Schlenk RF, Schaich M, et al. Acute Myeloid Leukemia (AML): different treatment strategies versus a common standard arm--combined prospective analysis by the German AML Intergroup. J Clin Oncol 2012; 30:3604.
  29. Jin J, Wang JX, Chen FF, et al. Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial. Lancet Oncol 2013; 14:599.
  30. Stone RM, Mandrekar S, Sanford BL, et al. The Multi-Kinase Inhibitor Midostaurin (M) Prolongs Survival Compared with Placebo (P) in Combination with Daunorubicin (D)/Cytarabine (C) Induction (ind), High-Dose C Consolidation (consol), and As Maintenance (maint) Therapy in Newly Diagnosed Acute Myeloid Leukemia (AML) Patients (pts) Age 18-60 with FLT3 Mutations (muts): An International Prospective Randomized (rand) P-Controlled Double-Blind Trial (CALGB 10603/RATIFY [Alliance]). Blood (ASH Annual Meeting Abstracts Plenary Scientific Session) 2015; 126:Abstract 6.
  31. Röllig C, Serve H, Hüttmann A, et al. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol 2015; 16:1691.
  32. Libura M, Giebel S, Piatkowska-Jakubas B, et al. Cladribine added to daunorubicin-cytarabine induction prolongs survival of FLT3-ITD+ normal karyotype AML patients. Blood 2016; 127:360.
  33. Holowiecki J, Grosicki S, Giebel S, et al. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol 2012; 30:2441.
  34. Holowiecki J, Grosicki S, Robak T, et al. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study. Leukemia 2004; 18:989.
  35. Burnett AK, Russell NH, Hills RK, et al. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial. J Clin Oncol 2013; 31:3360.
  36. Bishop JF, Matthews JP, Young GA, et al. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood 1996; 87:1710.
  37. Weick JK, Kopecky KJ, Appelbaum FR, et al. A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study. Blood 1996; 88:2841.
  38. Phillips GL, Reece DE, Shepherd JD, et al. High-dose cytarabine and daunorubicin induction and postremission chemotherapy for the treatment of acute myelogenous leukemia in adults. Blood 1991; 77:1429.
  39. Schiller G, Gajewski J, Nimer S, et al. A randomized study of intermediate versus conventional-dose cytarabine as intensive induction for acute myelogenous leukaemia. Br J Haematol 1992; 81:170.
  40. Löwenberg B, Pabst T, Vellenga E, et al. Cytarabine dose for acute myeloid leukemia. N Engl J Med 2011; 364:1027.
  41. Willemze R, Suciu S, Meloni G, et al. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol 2014; 32:219.
  42. Garcia-Manero G, Tambaro FP, Bekele NB, et al. Phase II trial of vorinostat with idarubicin and cytarabine for patients with newly diagnosed acute myelogenous leukemia or myelodysplastic syndrome. J Clin Oncol 2012; 30:2204.
  43. 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: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study. Blood 2004; 104:2467.
  44. http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf (Accessed on February 07, 2011).
  45. Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2011; 29:4189.
  46. Bradstock KF, Link E, Collins M, et al. A randomized trial of prophylactic palifermin on gastrointestinal toxicity after intensive induction therapy for acute myeloid leukaemia. Br J Haematol 2014; 167:618.
  47. Slichter SJ, Kaufman RM, Assmann SF, et al. Dose of prophylactic platelet transfusions and prevention of hemorrhage. N Engl J Med 2010; 362:600.
  48. Thomas X, Raffoux E, Renneville A, et al. Which AML subsets benefit from leukemic cell priming during chemotherapy? Long-term analysis of the ALFA-9802 GM-CSF study. Cancer 2010; 116:1725.
  49. Wheatley K, Goldstone AH, Littlewood T, et al. Randomized placebo-controlled trial of granulocyte colony stimulating factor (G-CSF) as supportive care after induction chemotherapy in adult patients with acute myeloid leukaemia: a study of the United Kingdom Medical Research Council Adult Leukaemia Working Party. Br J Haematol 2009; 146:54.
  50. Löwenberg B, van Putten W, Theobald M, et al. Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. N Engl J Med 2003; 349:743.
  51. Thomas X, Raffoux E, Botton Sd, et al. Effect of priming with granulocyte-macrophage colony-stimulating factor in younger adults with newly diagnosed acute myeloid leukemia: a trial by the Acute Leukemia French Association (ALFA) Group. Leukemia 2007; 21:453.
  52. Pabst T, Vellenga E, van Putten W, et al. Favorable effect of priming with granulocyte colony-stimulating factor in remission induction of acute myeloid leukemia restricted to dose escalation of cytarabine. Blood 2012; 119:5367.
  53. Gardner A, Mattiuzzi G, Faderl S, et al. Randomized comparison of cooked and noncooked diets in patients undergoing remission induction therapy for acute myeloid leukemia. J Clin Oncol 2008; 26:5684.
  54. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis 2011; 52:e56.
  55. Segal BH, Freifeld AG, Baden LR, et al. Prevention and treatment of cancer-related infections. J Natl Compr Canc Netw 2008; 6:122.
  56. http://www.nccn.org/professionals/physician_gls/pdf/aml.pdf (Accessed on July 10, 2015).
  57. Rowe JM, Kim HT, Cassileth PA, et al. Adult patients with acute myeloid leukemia who achieve complete remission after 1 or 2 cycles of induction have a similar prognosis: a report on 1980 patients registered to 6 studies conducted by the Eastern Cooperative Oncology Group. Cancer 2010; 116:5012.
  58. Germann N, Goffinet F, Goldwasser F. Anthracyclines during pregnancy: embryo-fetal outcome in 160 patients. Ann Oncol 2004; 15:146.
  59. Chelghoum Y, Vey N, Raffoux E, et al. Acute leukemia during pregnancy: a report on 37 patients and a review of the literature. Cancer 2005; 104:110.
  60. Pizzuto J, Aviles A, Noriega L, et al. Treatment of acute leukemia during pregnancy: presentation of nine cases. Cancer Treat Rep 1980; 64:679.
  61. Reynoso EE, Shepherd FA, Messner HA, et al. Acute leukemia during pregnancy: the Toronto Leukemia Study Group experience with long-term follow-up of children exposed in utero to chemotherapeutic agents. J Clin Oncol 1987; 5:1098.
  62. Cardonick E, Iacobucci A. Use of chemotherapy during human pregnancy. Lancet Oncol 2004; 5:283.
  63. Milojkovic D, Apperley JF. How I treat leukemia during pregnancy. Blood 2014; 123:974.
  64. Bakst RL, Tallman MS, Douer D, Yahalom J. How I treat extramedullary acute myeloid leukemia. Blood 2011; 118:3785.
  65. Bakst R, Wolden S, Yahalom J. Radiation therapy for chloroma (granulocytic sarcoma). Int J Radiat Oncol Biol Phys 2012; 82:1816.
  66. Fritz J, Vogel W, Bares R, Horger M. Radiologic spectrum of extramedullary relapse of myelogenous leukemia in adults. AJR Am J Roentgenol 2007; 189:209.
  67. Lee EY, Anthony MP, Leung AY, et al. Utility of FDG PET/CT in the assessment of myeloid sarcoma. AJR Am J Roentgenol 2012; 198:1175.
  68. Yamauchi K, Yasuda M. Comparison in treatments of nonleukemic granulocytic sarcoma: report of two cases and a review of 72 cases in the literature. Cancer 2002; 94:1739.
  69. Lan TY, Lin DT, Tien HF, et al. Prognostic factors of treatment outcomes in patients with granulocytic sarcoma. Acta Haematol 2009; 122:238.
  70. Tsimberidou AM, Kantarjian HM, Estey E, et al. Outcome in patients with nonleukemic granulocytic sarcoma treated with chemotherapy with or without radiotherapy. Leukemia 2003; 17:1100.
  71. Atfy M, Al Azizi NM, Elnaggar AM. Incidence of Philadelphia-chromosome in acute myelogenous leukemia and biphenotypic acute leukemia patients: And its role in their outcome. Leuk Res 2011; 35:1339.
  72. Nacheva EP, Grace CD, Brazma D, et al. Does BCR/ABL1 positive acute myeloid leukaemia exist? Br J Haematol 2013; 161:541.
  73. Kondo T, Tasaka T, Sano F, et al. Philadelphia chromosome-positive acute myeloid leukemia (Ph + AML) treated with imatinib mesylate (IM): a report with IM plasma concentration and bcr-abl transcripts. Leuk Res 2009; 33:e137.
  74. Ritchie DS, McBean M, Westerman DA, et al. Complete molecular response of e6a2 BCR-ABL-positive acute myeloid leukemia to imatinib then dasatinib. Blood 2008; 111:2896.
  75. Cho BS, Kim HJ, Lee S, et al. Successful interim therapy with imatinib prior to allogeneic stem cell transplantation in Philadelphia chromosome-positive acute myeloid leukemia. Eur J Haematol 2007; 79:170.
  76. Isoda A, Nakahashi H, Hoshino T, et al. Insufficient outcomes with imatinib mesylate: case report of Ph-positive acute myeloid leukemia evolving from myelodysplastic syndrome. Am J Hematol 2007; 82:501.
  77. Ueda K, Horiike S, Zen K, et al. Complete cytogenetic and molecular response to treatment with imatinib mesylate for philadelphia chromosome positive acute myeloid leukemia with multilineage dysplasia. Leuk Lymphoma 2006; 47:1967.
  78. Pompetti F, Spadano A, Sau A, et al. Long-term remission in BCR/ABL-positive AML-M6 patient treated with Imatinib Mesylate. Leuk Res 2007; 31:563.
  79. Jentsch-Ullrich K, Pelz AF, Braun H, et al. Complete molecular remission in a patient with Philadelphia-chromosome positive acute myeloid leukemia after conventional therapy and imatinib. Haematologica 2004; 89:ECR15.
  80. Swerdlow SH, Campo E, Harris NL, et al. World Health Organization classification of tumours of haematopoietic and lymphoid tissues, IARC Press, Lyon 2008.
  81. Weinberg OK, Arber DA. Mixed-phenotype acute leukemia: historical overview and a new definition. Leukemia 2010; 24:1844.
  82. Wolach O, Stone RM. How I treat mixed-phenotype acute leukemia. Blood 2015; 125:2477.
  83. Mejstrikova E, Volejnikova J, Fronkova E, et al. Prognosis of children with mixed phenotype acute leukemia treated on the basis of consistent immunophenotypic criteria. Haematologica 2010; 95:928.
  84. Matutes E, Pickl WF, Van't Veer M, et al. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 2011; 117:3163.