Acute Myeloid Leukemia

How to Cite This Chapter: Khalaf D, Crowther M, Hołowiecki J. Acute Myeloid Leukemia. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. Accessed July 07, 2020.
Last Updated: June 19, 2019
Last Reviewed: June 19, 2019
Chapter Information

Definition, Etiology, PathogenesisTop

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy that is characterized by the presence of a clone of transformed myeloid cells originating at early stages of myelopoiesis. The cells predominate in bone marrow and peripheral blood and infiltrate various organs, affecting their function.

Risk factors include exposure to ionizing radiation, benzene, and cytotoxic agents (alkylating drugs, topoisomerase inhibitors).

Classification had been based on morphology until some recurrent cytogenetic abnormalities were identified, which helped with better understanding of disease biology and choice of therapy. AML can be classified into de novo AML or secondary AML with antecedent blood cancer. There is also a subset that is therapy-related where prior radiation therapy or chemotherapy cause the emergence of a malignant clone.

AML with myelodysplasia-related changes (AML-MRC) is known to be of poor prognosis due to the higher incidence of cytogenetic abnormalities associated with poor risk, commonly in older patients with comorbidities, transfusion dependence, risk of catastrophic bleeding, and/or iron overload.

Clinical Features And Natural HistoryTop

1. General symptoms: Constitutional symptoms including fevers, weight loss, and drenching sweats in addition to fatigue and bone and joint pain.

2. Manifestations of anemia; thrombocytopenia with associated mucocutaneous bleeding, petechial rash, urogenital and/or gastrointestinal bleeding. Other features involve those of immunodeficiency with recurrent infection symptoms, including bacterial sepsis and fungal infections.

3. Manifestations of leukostasis associated with white blood cell (WBC) counts >100,000 cells/microL: Altered mental status, headache, visual disturbances, angina, features of hypoxemia caused by impaired pulmonary perfusion, and priapism.

4. Manifestations of leukemic infiltrates in various tissues and organs, more commonly seen in patients with monocytic leukemia: Leukemia cutis, gingival infiltrates, pulmonary infiltrates, splenomegaly and/or hepatomegaly, and/or lymphadenopathy. Central nervous system (CNS) leukemia is common in patients with higher WBC counts who present with various symptoms including headaches, visual changes, and nausea or vomiting.


Diagnostic Tests

1. Complete blood count (CBC): Any degree of pancytopenia with leukopenia, anemia and thrombocytopenia. Leukocytosis is also possible with accompanying left shift and pathognomonic circulating blasts.

2. Bone marrow aspiration and biopsy: Assessment by morphology, cytochemistry, immunophenotyping, cytogenetic analysis, and molecular studies to detect mutations using the myeloid next-generation sequencing panel. Such mutations could carry a prognostic significance or would indicate targeted therapy (see Treatment, below). Bone marrow biopsy gives an idea on cellularity, stromal abnormalities, or antecedent myeloid malignancy. The presence of Auer rods on bone marrow examination is pathognomonic of AML.

3. Other laboratory studies: Coagulation parameters, serum lactate dehydrogenase, uric acid, electrolytes, calcium, magnesium, and phosphate levels. Tumor lysis is common in patients with high WBC counts at presentation, hyperuricemia, hyperkalemia, hypocalcemia, and hyperphosphatemia. Acute kidney injury can be seen due to tumor lysis or leukostasis. Patients with high WBC counts may develop artifactual hyperkalemia, hypoxemia, and hypoglycemia due to the effects of leukemic cells after the samples are drawn.

Diagnostic Criteria

The diagnosis of AML is established in patients with ≥20% blasts (including myeloblasts and their equivalents: monoblasts, promonocytes, and megakaryoblasts). In certain situations the diagnosis of AML can be made regardless of the percentage of blasts: in patients with core-binding factor AML with inv(16) or t(8;21) or those with acute promyelocytic leukemia with t(15;17) as well as patients with granulocytic sarcoma.

Classification of risk groups (according to the European LeukemiaNet) is based on the results of cytogenetic and molecular studies. The adverse-risk group also includes secondary AML in patients after radiotherapy and/or chemotherapy, AML preceded by myelodysplastic syndrome (MDS), and AML with primary treatment resistance.

Differential Diagnosis

Infectious mononucleosis, acute lymphoblastic leukemia, large B-cell lymphoma, high-risk MDS, myeloproliferative neoplasms with high blast counts, leukemoid reaction, and recovering marrow (particularly in patients with recently treated vitamin B12 deficiency).


Therapeutic choice is tailored to patient-related and disease-related factors. Scoring systems such as the AML composite model for risk assessment and hematopoietic cell transplantation–specific comorbidity index (available at are helpful to evaluate the patient’s eligibility for therapy. These decisions should be used in specialized settings.

Individualized therapy is offered based on the patient’s Eastern Cooperative Oncology Group (ECOG) performance status (available at, comorbidities, disease biology, molecular mutations, and cytogenetics. Such tools assist the clinician in decision-making with regard to therapeutic choices and eligibility for allogeneic hematopoietic stem cell transplantation (HSCT) after remission induction.

1. Remission induction depends on the patient’s fitness for intensive chemotherapy. All patients receive induction treatment using the 3 + 7 regimen (a combination of daunorubicin and cytarabine). More intensive induction treatment using fludarabine, cytarabine, granulocyte colony-stimulating factor (G-CSF), and idarubicin—the FLAG-IDA regimen—may be offered to patients with secondary AML or therapy-related AML. In elderly patients or those with poor performance status hypomethylating agents (azacitidine or decitabine) can be used with palliative intent; this line of therapy provides good quality of life and transfusion independence. A specialized hematologist should be making decisions regarding therapy and patients should be cared for in an expert center familiar with the current best practices in treatment.

Outcomes of induction treatment: Complete remission (CR), CR with minimal residual disease (CR-MRD), CR with hematologic recovery (CR-H), CR with incomplete hematologic recovery (CR-i), partial remission (PR), or treatment failure in the case of nonresponse or progressive disease.

Criteria for CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) ≥1000/microL; platelet count ≥100 000/microL.

2. Remission consolidation: Postremission treatment is aimed at eradicating residual disease, including minimal residual disease (MRD) (presence of leukemic cells at a level producing no clinical manifestations and detectable only using sensitive methods [flow cytometry, molecular studies]). Regimens include high-dose cytarabine administered in 3 cycles.

3. Allogeneic hematopoietic stem cell transplantation (HSCT) for patients in the adverse-risk or intermediate-risk group who have good performance status and have both access to a bone marrow transplant center and donor available. This results in 5-year disease-free survival (DFS) rates of 40% to 60%. There is up to 20% transplant-related mortality at 1 year. In patients who are elderly or have poor performance status, allogeneic HSCT with a nonmyeloablative conditioning protocol can be used.

4. Supportive treatment:

 1) Tumor lysis prophylaxis should be provided to all patients initiating therapy. This includes IV fluids and allopurinol, a xanthine oxidase enzyme inhibitor that is considered to be one of the most effective drugs used to decrease urate levels. In patients with high disease burden and increased urate levels, use rasburicase, a recombinant urate oxidase enzyme that catalyzes uric acid and helps its elimination (see Tumor Lysis Syndrome).

2) Hyperleukocytosis (>100,000/microL): Hydroxyurea (INN hydroxycarbamide) 50 to 60 mg/kg/d until WBC counts decrease to <10,000/microL.

3) Transfusion support: Packed red blood cells (PRBCs) to maintain hemoglobin (Hb) >70 g/L, platelet concentrates to maintain platelet >10,000/microL or in patients with bleeding or coagulopathy.

4) Prevention of infections: Antifungal prophylaxis using posaconazole during the induction phase, antiviral prophylaxis using acyclovir until WBC count recovery. Preemptive antibacterial prophylaxis is not indicated.

5) Treatment of infections: see Febrile Neutropenia.

6) Symptom management: Antiemetic drugs and bowel routine.

7) Multidisciplinary team approach: Involve clinical dietitians for appropriate nutritional management, either enteral or parenteral, social workers for psychological counseling and coping mechanisms, and physiotherapy and occupational therapy for mobilization and prevention of deconditioning.


Severe or life-threatening complications may include neutropenic septicemia, end-organ damage or multiorgan failure, prolonged pancytopenia, and refractory thrombocytopenia with subsequent transfusion dependence. Iron overload, coagulopathy, and risk of intensive care unit (ICU) transfer for mechanical ventilation may all occur.


Clinical follow-up including examination and a CBC with differential count should be performed monthly for up to 6 months, then every 3 months for 1 year, then every 6 months for 2 years, and subsequently once a year.


Cure rates are highest in patients aged <60 years with favorable cytogenetic features and no unfavorable molecular features who achieve rapid CR during induction therapy. Combination chemotherapy alone may achieve cure in some favorable-risk patients with AML (60% cure rate). In selected low-risk adult patients highly intensive chemotherapy regimens may produce 5-year survival rates of 40%, while HSCT is associated with >60% cure rates in eligible patients who survive to transplantation and who do not die as a result of transplantation. In other individuals, who constitute the majority of the patient population, cure rates are 10% to 15%.

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