Acute myeloid leukemia (AML) is the most prevalent adult acute leukemia.1 According to the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, as many as 20,380 cases of AML will be diagnosed in 2023.2 The median age at diagnosis of AML is 69 years, with approximately two-thirds of those being at least 55 years of age.2 Survival is highly dependent on age; younger patients with AML have a 5-year survival rate of nearly 50%, while those older than 60 have a 5-year survival rate of less than 10%.3
AML is a neoplasm of myeloid progenitor cells, which serve as precursors for neutrophils, basophils, eosinophils, monocytes, dendritic cells, erythrocytes, and megakaryocytes.4 This hematologic malignancy typically develops from somatic mutations that become more common with age. Thus, the current World Health Organization (WHO) system classifies AML into subgroups based on genetic and cytogenetic alterations in addition to cell morphology.1
Acute promyelocytic leukemia (APL) is a rare and unique AML subtype distinguished by the PML-RARA fusion gene, caused by a translocation between chromosomes 15 and 17. APL is highly treatable, with 95% of patients surviving long-term.5,6
Acute Myeloid Leukemia Treatment
AML treatment is based on cytogenetic features known to affect prognosis. The following factors are known to be favorable alterations in non-APL AML7,8:
- NPM1 mutations (in the absence of FLT3-ITD)
- In-frame CEBPA mutations that affect the bZIP region
- RUNX1-RUNX1T1 fusion — t(8;21)(q22;q22.1)
- CBFB-MYH11 fusion — inv(16)(p13.1;q22) or t(16;16)(p13.1;q22)
- Absence of cytogenetic or molecular aberrations
Markers that confer an intermediate prognosis in patients with AML include7,8:
- NPM1 mutations (co-occurring with FLT3-ITD, in the absence of other adverse risk abnormalities)
- MLLT3-KMT2A fusion — t(9;11)(p21.3;q23.3)
- Translocations between MLL and the X chromosome — t(11;X)
- Dual mutations in DNMT3A and IDH1
- Trisomy karyotype (one or more trisomies)
- Molecularly not otherwise specified
- Other alterations not included in the “favorable” or “adverse” risk categories
Patients with AML have adverse or poor risk if they have7,8:
- TP53 mutations
- Mutations in ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2
- BCR-ABL1 fusion — t(9;22)(q34.1;q11.2)
- DEK-NUP214 fusion — t(6;9)(p23.3;q34.1)
- Rearrangements of KMT2A — t(v;11q23.3)
- KAT6A-CREBBP fusion — t(8;16)(p11.2;p13.3)
- GATA2 or EVI1/MECOM rearrangements or translocations — inv(3)(q21.3;q26.2) or t(3;3)(q21.3;q26.2)
- EVI1/MECOM rearrangements — t(3q26.2;v)
- Monosomy 5 or 7, or del(5q), or -17/abn(17p)
- Monosomal karyotype (2 or more autosomal monosomies)
- Complex karyotype (3 or more non-class-defining abnormalities)
Patients with APL have an alternate risk stratification scheme. These patients are considered low risk if they have 10,000 WBC/µL or fewer, and they are considered high risk if they have more than 10,000 WBC/µL.7
Treatment of Acute Myeloid Leukemia in Adults
Patients with newly diagnosed AML should undergo intensive induction therapy when possible. For those in the favorable-risk group, induction therapy typically consists of the 7+3 chemotherapy regimen, in which patients receive cytarabine 100 to 200 mg/m2 in a continuous infusion for 7 days with the addition of daunorubicin 90 mg/m2 for the first 3 days. If the patient has CD33-positive AML, clinicians should administer a single dose of gemtuzumab ozogamicin 3 mg/m2 on day 1, 2, 3, or 4, or 3 doses on days 1, 4, and 7.3,7
In place of daunorubicin in the 7+3 regimen, clinicians can also use idarubicin 12 mg/m2 or, for those older than 60 years, mitoxantrone 12 mg/m2. Adding cladribine to 7+3 chemotherapy may also improve survival rates.5 Additionally, favorable-risk AML may be treated with FLAG-IDA, which consists of3,7:
- Days 2 to 6: fludarabine 30 mg/m2
- Days 2 to 6, starting 4 hours after fludarabine: high-dose cytarabine (HiDAC) 2 g/m2 over the course of 4 hours
- Days 4 to 6: idarubicin 8 mg/m2
- Days 1 to 7: subcutaneous granulocyte colony-stimulating factor (G-CSF)
Guidelines established by the National Comprehensive Cancer Network (NCCN) recommend that patients with AML with FLT3-ITD or FLT3-TKD mutations undergo standard 7+3 therapy with cytarabine 200 mg/m2 and daunorubicin 60 mg/m2 in addition to midostaurin 50 mg orally every 12 hours on days 8 to 21.7
For patients with intermediate-risk AML, 7+3 chemotherapy with either daunorubicin or idarubicin is the preferred induction treatment for patients younger than 60 years, while older patients should receive a 7+3 regimen with mitoxantrone.7
Several induction treatment options for adverse-risk AML are available, including7:
- A 7+3 regimen with daunorubicin or idarubicin
- 7+3 chemotherapy consisting of 7 days of cytarabine and 3 days of mitoxantrone for patients aged 60 years and older
- HiDAC consisting of 6 days of a single 2-g/m2 dose every 12 hours or 4 days of 3 g/m2 every 12 hours, in addition to 3 days of daunorubicin 50 mg/m2 or idarubicin 12 mg/m2, plus 50 mg/m2 on days 1 to 5
- Low-dose cytarabine (LDAC) consisting of cytarabine 20 mg/m2/d on days 1 to 10 of each 28-day cycle in addition to venetoclax 1 dose per day orally in increasing doses (day 1, 100 mg; day 2, 200 mg; day 3, 400 mg; day 4+: 600 mg)
- FLAG-IDA with or without venetoclax
- Decitabine 20 mg/m2 on days 1 to 5 or days 1 to 10 of a 28-day cycle, in addition to venetoclax once daily orally in increasing doses (day 1, 100 mg; day 2, 200 mg; day 3+, 400 mg)
- Azacitidine 75 mg/m2 subcutaneously or intravenously (IV) on days 1 to 7 of a 28-day cycle, in addition to venetoclax 1 dose per day orally in increasing doses (day 1, 100 mg; day 2, 200 mg; day 3+, 400 mg)
- Low-intensity therapy consisting of either azacitidine 75 mg/m2 on days 1 to 7 of each 28-day cycle or decitabine 20 mg/m2 on days 1 to 5 or days 1 to 10 of each 28-day cycle
Younger patients with AML may experience better outcomes when they are treated with high-dose cytarabine or other nucleoside analogs in addition to gemtuzumab ozogamicin.9
Patients with therapy-related AML or AML with myelodysplasia-related changes (≥20% blasts and ≥50% dysplastic cells in at least 2 myeloid lineages) are more likely to have mutations or cytogenetic changes that make malignant cells resistant to therapy. These patients should be treated with one of the following regimens: standard 7+3 with daunorubicin or idarubicin, decitabine plus venetoclax, azacitidine plus venetoclax, LDAC plus venetoclax, or low-intensity therapy. This patient population can also be treated with 1 cycle of CPX-351 (a liposomal encapsulation of cytarabine 100 mg/m2 and daunorubicin 44 mg/m2) on days 1, 3, and 5.1,5,7
Some patients with AML, including older patients and those with comorbidities or poor performance status, should not undergo intensive induction therapy. Instead, these patients should be given regimens based on their genetic mutations. The preferred regimens for patients with IDH1 or IDH2 mutations include azacitidine and venetoclax, azacitidine and ivosidenib, decitabine and venetoclax, ivosidenib monotherapy, or enasidenib monotherapy. Patients with FLT3 mutations may be given azacitidine and venetoclax or decitabine and venetoclax. When patients with AML lack actionable mutations, venetoclax in addition to azacitidine or decitabine can be considered. Alternative regimens for this group include LDAC with or without venetoclax, LDAC and glasdegib, LDAC monotherapy, azacitidine or decitabine monotherapy, or — for patients with CD-33-positive disease — gemtuzumab ozogamicin monotherapy. For patients older than 60 years, the American Society of Hematology suggests monotherapy with LDAC or a hypomethylating agent.1,3,5,7,9,10
If patients with AML experience spread of disease to the central nervous system (CNS), clinicians should administer intrathecal chemotherapy twice weekly until no signs of CNS disease remain. Patients with a history of neurologic symptoms should then receive intrathecal chemotherapy once per week for an additional 4 to 6 weeks.7
Patients with AML should undergo bone marrow biopsy and aspirate within 2 to 3 weeks of beginning induction therapy. If a patient who received standard-dose cytarabine induction therapy has residual disease with more than 20% cellularity, the following reinduction regimens may be used7:
- HiDAC: 3 to 4 cycles of cytarabine 1.5 to 3 g/m2 over 3 hours every 12 hours on days 1, 3, and 5 or days 1, 2, and 3
- Standard 7+3 chemotherapy
- A standard 7+3 regimen with mitoxantrone for patients 60 years of age and older
- A standard 7+3 regimen in addition to midostaurin
- One cycle of CPX-351 (if previously used for induction therapy) on days 1, 3, and 5
Patients with hypocellularity in addition to more than 5% blasts should be treated with a standard 7+3 regimen, 7+3 in addition to mitoxantrone for those older than 60 years, 7+3 plus midostaurin, HiDAC, or intermediate-dose cytarabine.7
If AML does not respond to induction or reinduction therapy, clinicians may want to consider hematopoietic stem cell transplantation (HSCT) if the patient is a candidate. Additionally, patients diagnosed with favorable-risk, intermediate-risk, or adverse-risk AML who have residual disease following induction therapy may be given regimens for relapsed or refractory AML.7
Patients who achieve a complete response should undergo consolidation therapy as outlined in Table 1.7
Table 1. Consolidation Therapy for Adult Patients With AML
|Favorable-Risk AML||AML With FLT3-ITD or FLT3-TKD||Intermediate-Risk AML||Adverse-Risk AML|
|Patients aged <60 y||Cytarabine 3 g/m2 over 3 h every 12 hours on days 1, 3, and 5 or days 1, 2, and 3 for 3-4 cycles; if CD33-positive or NPM1-mutated with wild-type FLT3, add gemtuzumab ozogamicin 3 mg/m2 on day 1 for 2 cycles||Cytarabine 1.5-3 g/m2 over 3 h every 12 h on days 1, 3, and 5 or days 1, 2, and 3 for 3-4 cycles, and midostaurin 50 mg twice per day on days 8 to 21 for 4 cycles||Cytarabine 1.5-3 g/m2 over 3 h every 12 h on days 1, 3, and 5 or days 1, 2, and 3 for 3-4 cycles||Cytarabine 1.5-3 g/m2 over 3 h every 12 h on days 1, 3, and 5 or days 1, 2, and 3 for 3-4 cycles|
|Cytarabine 1-1.5 g/m2 every 12 h on days 1 to 4 and daunorubicin 60 mg/m2 on day 1 of first cycle and days 1 and 2 of second cycle for 2 cycles;if CD33-positive, gemtuzumab ozogamicin 3 mg/m2 on day 1 for 2 cycles||Cytarabine 1.5-3 g/m2 over 3 h every 12 h on days 1, 3, and 5 or days 1, 2, and 3 for 3-4 cycles||If CD33-positive: Cytarabine 1-1.5 g/m2 every 12 h on days 1 to 4 for 2 cycles; daunorubicin 60 mg/m2 on day 1 of first cycle and days 1 and 2 of second cycle; gemtuzumab ozogamicin 3 mg/m2 on day 1||If CPX-351 given during induction:CPX-351 (cytarabine 65 mg/m2 and daunorubicin 29 mg/m2) on days 1 and 3 for 1-2 cycles|
|If CD33-positive: Cytarabine 1-1.5 g/m2 every 12 h on days 1 to 4 for 2 cycles; daunorubicin 60 mg/m2 on day 1 of first cycle and days 1 and 2 of second cycle; gemtuzumab ozogamicin 3 mg/m2 on day 1||HSCT||If patient received lower-intensity induction therapy: Continue lower-intensity regimen|
|Patients aged ≥60 y||Cytarabine 100-200 mg/m2 over 5-7 d for 1-2 cycles; may also add idarubicin 10 mg/m2 or daunorubicin 45 mg/m2 or mitoxantrone 12 mg/m2 for 3 d||Cytarabine 1-1.5 g/m2 over 3 h every 12 h on days 1, 3, and 5 or days 1, 2, and 3 for 3-4 cycles, and midostaurin 50 mg twice daily on days 8-21 for 4 cycles||Cytarabine 1-1.5 g/m2 in 4-6 doses for 1-2 cycles||If patient received lower-intensity induction therapy: Continue lower-intensity regimen until disease progression or unacceptable toxicity10|
|Cytarabine 1-1.5 g/m2 in 4-6 doses for 1-2 cycles||HSCT||HSCT||If CPX-351 given during induction:CPX-351 (cytarabine 65 mg/m2 and daunorubicin 29 mg/m2) on days 1 and 3 for 1-2 cycles|
|If CD33-positive:Cytarabine 1-1.5 g/m2 in 4-6 doses for 1-2 cycles and daunorubicin 60 mg/m2 on day 1 of first cycle or days 1 to 2 of second cycle and gemtuzumab ozogamicin 3 mg/m2 on day 1 for 2 cycles||If intermediate-dose cytarabine given during induction therapy:Continue regimen containing intermediate-dose cytarabine|
HSCT = hematopoietic stem cell transplant.
From NCCN guidelines.7
Maintenance therapy is only recommended for select groups of patients with AML who have gone into remission (absolute neutrophil count >1000/mm3 and platelet count >100,000/mm3 in the peripheral blood and <5% blasts in the bone marrow).5
Patients with AML who went into remission following intensive induction therapy and consolidation therapy should receive maintenance therapy of ONE of the following7:
- Days 1 to 14 of each 28-day cycle: azacitidine 300 mg orally;
- Days 1 to 7 or days 1 to 5, day 8, and day 9 of each 28-day cycle: azacitidine 75 mg/m2 IV; or
- Days 1 to 5 of each 28-day cycle: decitabine 20 mg/m2 IV
Patients with a history of AML with FLT3-ITD mutations who went into remission following HSCT should receive ONE of the following1,7:
- Three 28-day cycles of sorafenib 200 mg orally twice daily, followed by sorafenib 400 mg orally twice daily until the patient has received 24 months of therapy;
- Twelve 28-day cycles of midostaurin 50 mg twice daily; or
- Up to 26 28-day cycles of gilteritinib 120 mg once per day
Managing Relapsed or Refractory Acute Myeloid Leukemia in Adults
Clinical trials are a good option for the treatment of relapsed/refractory AML. Alternatively, patients with actionable mutations should receive targeted treatment.11
Patients who can tolerate aggressive therapy may be given regimens such as fludarabine, cytarabine, and filgrastim (FLAG); mitoxantrone, etoposide, and cytarabine (MEC); high-dose or standard-dose cytarabine and mitoxantrone; high-dose etoposide and cyclophosphamide; or idarubicin and cytarabine. Less-aggressive therapy options include regimens containing LDAC, azacitidine, decitabine, or gemtuzumab ozogamicin.5,7
Pediatric Acute Myeloid Leukemia Management
For induction therapy, pediatric patients with favorable-risk or intermediate-risk AML generally receive 2 cycles of induction therapy and, if they have CD33-positive disease, gemtuzumab ozogamicin. The most common chemotherapy regimen includes cytarabine for 10 days followed by daunorubicin for 3 days. Other agents such as targeted therapies may also be added, especially for patients with high-risk AML. For example, children with FLT3-ITD should receive sorafenib, midostaurin, or another FLT3 inhibitor.12-14
If patients have minimal residual disease (MRD) positivity following induction therapy, they should undergo HSCT, if possible. Patients who are MRD-negative should receive another 2 to 3 cycles of chemotherapy.12
Patients with pediatric relapsed/refractory AML should generally be enrolled in clinical trials. Allogeneic HSCT should also be considered.12
Children with Down syndrome who develop AML should be treated with low-dose chemotherapy regimens to reduce toxicity since patients in this population tend to have better outcomes.15
Maintenance therapy is typically not recommended for pediatric AML because it does not generally provide a survival benefit.14
Management of Acute Promyelocytic Leukemia
Low-Risk Acute Promyelocytic Leukemia
Patients with APL are started on a daily regimen of all-trans retinoic acid (ATRA) 45 mg/m2 given in 2 divided doses. This induction treatment is generally combined with arsenic trioxide 0.15 mg/kg/d IV. Alternatively, arsenic trioxide may be given at a dose of 0.3 mg/kg on days 1 to 5 of week 1 and 0.25 mg/kg twice per week for weeks 2 through 8.5,7
Consolidation therapy for APL may be given when platelet counts fall below 100,000 and absolute neutrophil counts fall below 1000, or when bone marrow aspirate and biopsy confirm that the marrow contains fewer than 5% blasts and no abnormal promyelocytes.7
If induction therapy consisted of lower-dose arsenic trioxide, clinicians should continue to give this medication at a dosage of 0.15 mg/kg for 5 days per week for 4 weeks. This cycle should be repeated every 8 weeks for a total of 4 cycles. Additionally, patients should receive ATRA 45 mg/m2/d for 2 weeks. This cycle should be repeated every 4 weeks for a total of 7 cycles.7
Patients who received a higher dose of arsenic trioxide during induction therapy should receive three 56-day consolidation cycles consisting of ATRA 45 mg/m2/d in 2 divided doses on days 1 to 14 and 29 to 42, combined with arsenic trioxide 0.3 mg/kg on week 1, days 1 to 5, and arsenic trioxide 0.25 mg/kg twice per week on weeks 2 through 4. This should be followed by a fourth cycle consisting of ATRA 45 mg/m2/d for days 1 to 14, arsenic trioxide 0.3 mg/kg/d on week 1, days 1 to 5, and arsenic trioxide 0.25 mg/kg twice per week for weeks 2 to 4 of a 28-day cycle.7
When arsenic trioxide is contraindicated for induction therapy, it may be replaced with idarubicin 12 mg/m2 on days 2, 4, 6, and 8 or days 2, 4, and 6. During consolidation therapy, clinicians should administer the following 3 cycles7:
- ATRA 45 mg/m2 for 15 days and idarubicin 5 mg/m2 for 4 days
- ATRA 45 mg/m2 for 15 days and mitoxatrone 10 mg/m2 for 3 days
- ATRA 45 mg/m2 for 15 days and idarubicin 12 mg/m2 for 1 day
Alternatively, clinicians may give gemtuzumab ozogamicin 9 mg/m2 in a single dose on day 5 along with ATRA induction therapy. For these patients, consolidation therapy consists of ATRA 45 mg/m2/d in 2 divided doses on weeks 1 to 2, 5 to 6, 9 to 10, 13 to 14, 17 to 18, 21 to 22, and 25 to 26. Additionally, gemtuzumab ozogamicin 9 mg/m2 is given once per month.7
High-Risk Acute Promyelocytic Leukemia
The NCCN guidelines list 3 preferred regimens for the treatment of high-risk APL7:
- Induction therapy — Days 1 to 36: ATRA 45 mg/m2/d in 2 divided doses; days 2, 4, 6, and 8: idarubicin 6 to 12 mg/m2 (age-adjusted dose); days 9 to 36: arsenic trioxide 0.15 mg/kg in a 2-hour infusion.
Consolidation therapy — One 28-day cycle of ATRA 45 mg/m2/d and arsenic trioxide 0.15 mg/kg/d, followed by 3 cycles of ATRA 45 mg/m2 for 7 days every 2 weeks and 1 cycle of arsenic trioxide 0.15 mg/kg/d for 5 days for 5 weeks.
- Induction therapy — ATRA 45 mg/m2/d in 2 divided doses, arsenic trioxide 0.15 mg/kg/d, and gemtuzumab ozogamicin 9 mg/m2 in a single dose on day 1, 2, 3, or 4.
Consolidation therapy — 7 cycles of ATRA 45 mg/m2/d for 2 weeks every 4 weeks and 4 cycles of arsenic trioxide 0.15 mg/kg/d for 5 days per week for 4 weeks every 8 weeks. Alternatively, gemtuzumab ozogamicin 9 mg/m2 in a single dose may be administered every 4 to 5 weeks if ATRA or arsenic trioxide produces significant toxicity.
- Induction therapy — ATRA 45 mg/m2/d in 2 divided doses, in addition to arsenic trioxide 0.3 mg/kg on days 1 to 5 for week 1 and arsenic trioxide 0.25 mg/kg twice per week for weeks 2 through 8. Additionally, clinicians should administer gemtuzumab ozogamicin 6 mg/m2 in a single dose on day 1, 2, 3, or 4.
Consolidation therapy — ATRA 45 mg/m2/d for 2 weeks every 4 weeks, in addition to arsenic trioxide 0.3 mg/kg on days 1 to 5 for week 1 and arsenic trioxide 0.25 mg/kg twice per week for weeks 2 to 4. Alternatively, gemtuzumab ozogamicin 9 mg/m2 in a single dose may be administered every 4 to 5 weeks if ATRA or arsenic trioxide produces significant toxicity.
Other recommended regimens include induction therapy with ATRA in addition to idarubicin or the combination of daunorubicin and cytarabine.7
Patients with high-risk APL and cardiac issues may require alternate dosing schema. Those with a low ejection fraction should be given regimen 2 or 3 as listed above, with gemtuzumab ozogamicin given on day 1 during induction therapy. Patients with a prolonged QTc interval should not be given arsenic trioxide and should instead use induction regimens that combine ATRA with gemtuzumab ozogamicin, idarubicin, or daunorubicin plus cytarabine.7
Relapsed Acute Promyelocytic Leukemia
Patients who experience relapse within 6 months of a regimen containing ATRA and arsenic trioxide should be treated with an anthracycline-based regimen. When patients experience an early relapse after a regimen consisting of ATRA and an anthracycline, they should be moved to an arsenic trioxide-based regimen.7
Relapses that occur after 6 months should be treated with arsenic trioxide in addition to ATRA and/or anthracycline and/or gemtuzumab ozogamicin.7
Intrathecal methotrexate or cytarabine should be considered as a prophylactic measure upon second remission. HSCT may also be considered for patients with continued relapses or an absence of molecular remission as measured by polymerase chain reaction (PCR).7
Monitoring Side Effects, Adverse Events, and Drug-Drug Interactions
Patients with AML should be monitored for myelosuppression, which may occur as both a symptom of AML and a side effect of treatment. Supportive care during the treatment of AML typically includes5:
- Red blood cell and/or platelet transfusions
- Administration of growth factors, including colony-stimulating factors, thrombopoietin mimetics, and erythropoiesis-stimulating agents
- Prophylactic antimicrobial therapy, especially for patients with severe neutropenia
Table 2 describes some of the common adverse events, drug-drug interactions, and considerations for use in special populations for common AML pharmacotherapies.
Table 2. Side Effect Profiles for AML Therapies
|Drug||Most Common Adverse Events||Side Effects that May Necessitate Discontinuation or Modification||Drug-Drug Interactions||Use in Special Populations|
|ATRA||Headache, fever, nausea, vomiting, abdominal pain, skin rash, dry skin, mucous membrane dryness, bone pain, shivering, upper respiratory disorders, shortness of breath, chest discomfort, hemorrhage, infections, peripheral edema||Intracranial hypertension||Inhibitors and inducers of CYP3A4, vitamin A, antifibrinolytic agents||Not recommended in pregnant or lactating patients|
|Arsenic trioxide||Nausea, vomiting, diarrhea, abdominal pain, hepatic toxicity, fever, swelling, headache, dizziness, fatigue, insomnia, shortness of breath, tachycardia, QTc prolongation, leukocytosis, neutropenia, thrombocytopenia, hyperglycemia, hypokalemia, hypomagnesemia||Differentiation syndrome, prolonged QTc interval, encephalopathy, hepatotoxicity||Medications that prolong the QT/QTc interval lead to electrolyte abnormalities or cause hepatotoxicity||Not recommended in pregnant or lactating patients; monitor patients with a history of severe renal or hepatic toxicity|
|Azacitidine||Nausea, vomiting, diarrhea, constipation, fever, weakness, swelling at the injection site, skin rash, petechiae, upper respiratory infection, anemia, leukopenia, thrombocytopenia, neutropenia, hypokalemia||Cytopenias, renal toxicity||None indicated||Not recommended in pregnant or lactating patients or in patients with advanced malignant hepatic tumors|
|Cladribine||Headache, nausea, vomiting, diarrhea, anorexia, cough, fatigue, fever, skin rash, administration site reactions, febrile neutropenia||Neural toxicity, renal toxicity||None indicated||Not recommended in pregnant or lactating patients|
|Clofarabine||Nausea, vomiting, diarrhea, febrile neutropenia, headache, rash, pruritus, pyrexia, fatigue, palmar-plantar erythrodysesthesia syndrome, anxiety, flushing, mucosal inflammation||Hypotension, infection, exfoliative or bullous rash, systemic inflammatory response syndrome, capillary leak syndrome, venous occlusive disease of the liver, hepatotoxicity, renal toxicity||None indicated||Not recommended in pregnant or lactating patients|
|CPX-351||Skin rash, swelling, hemorrhage, nausea, vomiting, diarrhea, constipation, anorexia, abdominal pain, headache, cough, shortness of breath, fatigue, musculoskeletal pain, arrhythmia, pneumonia, bacteremia, sleep disorders, febrile neutropenia||Impaired cardiac function, severe hypersensitivity reaction, signs of acute copper toxicity||Regularly monitor cardiac or hepatic function when administered with cardiotoxic or hepatotoxic agents, respectively||Not recommended in pregnant or lactating patients|
|Cyclophosphamide||Neutropenia, fever, alopecia, nausea, vomiting, diarrhea||Severe hemorrhagic cystitis||Protease inhibitors, ACE inhibitors, natalizumab, paclitaxel, thiazide diuretics, zidovudine, anthracyclines, cytarabine, pentostatin, trastuzumab, G-CSF, GM-CSF, amphotericin B, indomethacin, azathioprine, busulfan, etanercept, metronidazole, tamoxifen, coumarins, cyclosporine, depolarizing muscle relaxants||Contraindicated in those with urinary outflow obstruction and in pregnant or lactating patients|
|Cytarabine||Anorexia, nausea, vomiting, diarrhea, oral and anal inflammation or ulceration, hepatic dysfunction, fever, rash, thrombophlebitis, bleeding||None indicated||β-acetyldigoxin, gentamicin||Not recommended in pregnant patients|
|Daunorubicin||Alopecia, nausea, vomiting, mucositis, diarrhea, abdominal pain||None indicated||None indicated||May be more likely to cause cardiotoxicity in pediatric and elderly populations; patients with renal or hepatic impairment should receive a decreased dose; not recommended for use in pregnant patients|
|Decitabine||Fever, neutropenia, thrombocytopenia, anemia||None indicated||None indicated||Not recommended in pregnant or lactating patients|
|Enasidenib||Nausea, vomiting, diarrhea, anorexia, elevated bilirubin||Severe differentiation syndrome||None indicated||Not recommended in pregnant or lactating patients|
|Fludarabine||Fever, infection, nausea, vomiting, fatigue, anorexia, cough, weakness, neutropenia, anemia, thrombocytopenia||Hemolysis, neurotoxicity||Pentostatin||Reduce dose for patients with creatinine clearance 30-70 mL/min/1.73 m2;contraindicated in patients with creatinine clearance <30 mL/min/1.73 m2; Not recommended in individuals trying to get pregnant or in pregnant or lactating patients|
|Gemtuzumab ozogamicin||Hemorrhage, infection, fever, nausea, vomiting, constipation, headache, skin rash, mucositis, increased AST, increased ALT||Infusion-related reactions, liver toxicity, severe hemorrhage, persistent thrombocytopenia, persistent neutropenia, veno-occlusive disease||None indicated||Not recommended in pregnant or lactating patients|
|Glasdegib||Fatigue, hemorrhage, musculoskeletal pain, nausea, anorexia, constipation, changes in taste, mucositis, swelling, shortness of breath, skin rash, anemia, febrile neutropenia, thrombocytopenia||Prolonged QTc interval, persistent thrombocytopenia, persistent neutropenia||Strong inducers or inhibitors of CYP3A4, QTc-prolonging drugs||Not recommended in pregnant or lactating patients|
|Idarubicin||Infection, nausea, vomiting, abdominal cramps, diarrhea, hair loss, hemorrhage, mucositis, skin reactions, changes in mental status, fever, headache||None indicated||None indicated||Not recommended in pregnant or lactating patients|
|Ivosidenib||Diarrhea, nausea, vomiting, anorexia, abdominal pain, fatigue, swelling, joint pain, shortness of breath, mucositis, skin rash, leukocytopenia, decreased hemoglobin, thrombocytopenia, leukocytosis, neutropenia, hyperglycemia, increased ALP, increased AST, hypokalemia, hypophosphatemia, hyponatremia, hypocalcemia, hypomagnesemia, hyperuricemia, increased creatinine, prolonged QT interval||Prolonged QTc interval, Guillain-Barré syndrome||Strong or moderate CYP3A4 inhibitors, strong CYP3A4 inducers, sensitive CYP3A4 substrates, medications that prolong the QTc interval||Not recommended in pregnant or lactating patients|
|Midostaurin||Nausea, vomiting, headache, petechiae, mucositis, musculoskeletal pain, nosebleeds, infection, upper respiratory infection, febrile neutropenia, hyperglycemia||Pulmonary toxicity, persistent thrombocytopenia, persistent neutropenia, persistent low hemoglobin levels||Strong inhibitors and inducers of CYP3A4||Not recommended in pregnant or lactating patients|
|Mitoxantrone||Nausea, vomiting, diarrhea, mucositis, fever, hemorrhage, infection, hair loss, shortness of breath, cough, myelosuppression||None indicated||None indicated||Not recommended in pregnant or lactating patients|
|Sorafenib||Diarrhea, nausea, anorexia, abdominal pain, skin loss, fatigue, infection, hair loss, hand-foot skin reaction, skin rash, hemorrhage, hypertension||Cardiovascular events, severe hemorrhage, dermatologic toxicity, gastrointestinal perforation, liver toxicity||Strong inducers of CYP3A4||Not recommended in individuals trying to get pregnant or in pregnant or lactating patients|
|Venetoclax||Fatigue, nausea, vomiting, diarrhea, constipation, cough, shortness of breath, upper respiratory infection, pneumonia, musculoskeletal pain, back pain, abdominal pain, oropharyngeal pain, edema, fever, dizziness, hemorrhage, sepsis, rash, hypotension, neutropenia, anemia, thrombocytopenia||Severe neutropenia||Strong inducers and inhibitors of CYP3A, warfarin, P-gp substrates||Not recommended in pregnant or lactating patients|
ACE = angiotensin-converting enzyme; ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; ATRA = all-trans retinoic acid; G-CSF = granulocyte colony-stimulating factor; GM-CSF = granulocyte-macrophage colony-stimulating factor; P-gp = P-glycoprotein.
From FDA-approved prescribing information.16-31
Acute Myeloid Leukemia Treatment Guidelines
Numerous associations have created evidence-based guidelines to assist clinicians with decision-making for patients with AML.
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Acute Myeloid Leukemia — Version 3.2023
- National Cancer Institute’s Acute Myeloid Leukemia Treatment (PDQ®)-Health Professional Version
- National Cancer Institute’s Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®)-Health Professional Version
- American Society of Hematology 2020 Guidelines for Treating Newly Diagnosed Acute Myeloid Leukemia in Older Adults
- Bhansali RS, Pratz KW, Lai C. Recent advances in targeted therapies in acute myeloid leukemia. J Hematol Oncol. 2023;16(1):29. doi:10.1186/s13045-023-01424-6
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Maureen McNulty studied molecular genetics and English at Ohio State University. She has spent more than a decade researching the genetic causes of — and possible treatments for — multiple types of cancer. Maureen is now a medical writer who is passionate about helping people use science to enrich their lives.