Acute Myeloid Leukemia Treatment Protocols 

Updated: May 09, 2017
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Treatment Protocols

Treatment protocols for acute myeloid leukemia (AML) are provided below, including a general treatment approach and treatment recommendations for relapsed or refractory disease. [1]

General treatment approach for acute myeloid leukemia

Fit patients (<60-65 years, select patients up to age 75 y) receive intensive therapy. Treatment includes induction therapy and postremission therapy (consolidation). Non–low-risk patients are evaluated for stem cell transplantation in first remission.

Less-fit patients (70-75 years and older, or younger patients with significant comorbidities) receive low-intensity therapy. Select less-fit patients with highly proliferative disease may be considered for intensive therapy

Treatment recommendations for patients <60y or for select patients ≤75y (good performance status, minimal or no comorbidities)

Induction therapy:

Combination of cytarabine and anthracycline or anthracenedione is recommended [2, 3, 4, 5] :

  • Cytarabine 100-200 mg/m 2 continuous IV infusion for 7d plus  idarubicin 12 mg/m 2/day for 3d or  daunorubicin 60-90 mg/m 2/day for 3d
  • Follow-up bone marrow to assess remission is typically done 7-14d after completion of induction chemotherapy, except for patients with acute promyelocytic leukemia (APL) (see APL guidelines) [6]

High-dose cytarabine plus anthracycline/anthracenedione (various regimens, such as idarubicin + high-dose cytarabine) [7, 8] :

  • Cytarabine 2-3 g/m 2 q12h for 3d plus  idarubicin 12 mg/m 2/day for 3d for one cycle or
  • Cytarabine 2-3 g/m 2 q12h for 3d plus  daunorubicin 45-60 mg/m 2 day for 3d for one cycle [6]

Midostaurin for newly diagnosed AML with FLT3 mutation-positive:

  • Cytarabine 200 mg/m2 IV on days 1-7 plus daunorubicin IV 60 mg/m 2/day on days 1-3 plus midostaurin 50 mg PO BID on days 8-21 of each 28-day cycle for up to two induction cycles [9]

Cladribine-based therapy:

  • Cytarabine 200 mg/m 2 continuous infusion for 7d plus daunorubicin 60 mg/m 2 for 3d plus cladribine 5 mg/m 2 for 5d [10]

Postremission therapy (consolidation) [2, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20] :

All patients should be assessed for risk of relapse. Specific drug regimens are recommended based on a patient’s risk of relapse.

Better-risk patients:

Cytogenetics [inv(16) or t(16;16), t(8;21)] and molecular abnormalities (normal cytogenetics: with NPM 1 mutation or isolated CEBPA mutation in the absence of FLT3-ITD):

  • High-dose cytarabine 3 g/m 2 IV over 3h every 12h on days 1, 3, and 5 for four cycles [6] or
  • High-dose cytarabine 3 g/m 2 IV over 3h every 12h on days 1, 3, and 5 for two cycles plus  autologous stem cell transplantation [6]

Intermediate-risk patients:

Cytogenetics [normal cytogenetics, +8, t(9;11), other nondefined] and molecular abnormalities [normal cytogenetics: t(8;21), inv(16), t(16;16): with c-KIT mutation]:

  • High-dose cytarabine 3 g/m 2 IV over 3h every 12h on days 1, 3, and 5 for four cycles or allogeneic stem cell transplantation

High-risk patients:

Cytogenetics [complex (≥3 clonal chromosomal abnormalities), -5, 5q-, -7, 7q-, 11q23 - non t(9;11), inv(3), t(3;3), t(6;9), t(9;22)] and molecular abnormalities (normal cytogenetics: FLT3-ITD mutation), prior antecedent hematologic disorder (AHD):

  • Allogeneic stem cell transplantation or
  • Clinical trial or
  • High-dose cytarabine 3 g/m 2 IV over 3h every 12h on days 1, 3, and 5; if clinical trial not available or
  • High-dose cytarabine (3 g/m 2 every 12 h on Days 1, 3, and 5) plus  midostaurin 50 mg PO BID on days 8-21 of each 28-day cycle for up to 4 consolidation cycles, followed by continuous midostaurin [9]

Treatment recommendations for patients ≥60y [21, 22, 23, 24] :

  • There is no standard therapy for this patient population; a clinical trial is preferred
  • The following low-intensity therapies are recommended for patients ≥60y: azacytidine 75 mg/m 2 IV or SC for 7d every 4-5wk or  decitabine 20 mg/m 2 IV daily for 5d every 4-5wk or low-dose cytarabine 20 mg SC BID for 10d every 4wk
  • In patients with a high WBC count (especially >30,000/μL) who are unlikely to respond to low-intensity therapy, consider therapies as in younger patients; however, tolerance and response may be poor

Treatment recommendations for relapsed or refractory disease

See the list below:

  • Response rates depend on duration of first remission [25]
  • Patients in complete remission (CR) longer than 2y have a 60% chance of responding to front-line regimens
  • Patients in CR for 1-2y have a 40% chance of responding to front-line regimens; clinical trials are preferred
  • Patients in CR less than 1y are unlikely to respond to front-line regimens and should be referred for clinical trials
  • The prognosis for patients beyond first salvage is very poor [26]

Recommended chemotherapy regimens for relapsed or refractory disease

Mitomycin, etoposide, and cytarabine (MEC) [27] :

  • Etoposide 80 mg/m 2 IV over 1h plus
  • Cytarabine 1 g/m 2 IV over 6h plus
  • Mitoxantrone 6 mg/m 2; all three drugs should be given daily for 6d or

CLAG-M (cladribine, cytarabine, mitoxantrone, and filgrastim) [28] :

  • Cladribine 5 mg/m 2 IV over 2h daily for 5d plus
  • Cytarabine 2 mg/m 2 IV over 4h daily for 5d, with each dose starting 2h after cladribine plus
  • Mitoxantrone 10 mg/m 2 IV for 3d plus
  • Filgrastim (Neupogen) 300 µg for 6d starting 24h prior to chemotherapy or

FLAG-IDA (fludarabine, cytarabine, idarubicin, and filgrastim) [29] :

  • Fludarabine 30 mg/m 2/day IV over 30min on days 1-5
  • Cytarabine (Ara-C) 2 g/m 2/day IV over 4h; 4h after fludarabine on days 1-5
  • Idarubicin 10 mg/m 2/day IV on days 1-3
  • Filgrastim  5 µg/kg/day SC to begin on day 6 until neutrophil recovery