Acute leukemias are malignant neoplastic diseases that arise from either the lymphoid or myeloid cell line. Acute lymphocytic leukemia (ALL) is the most common childhood malignancy, whereas acute myeloid leukemia (AML) primarily affects adults. The underlying cause of acute leukemia is rarely identifiable, but risk factors include prior chemotherapy and radiation therapy, and hereditary syndromes such as Down syndrome. AML is also associated with preexisting hematologic disorders (e.g., myelodysplastic disorder, myeloproliferative disorders). Acute leukemias are characterized by the proliferation of immature, nonfunctional WBCs (blasts) in the bone marrow, which impairs normal hematopoiesis. This leads to pancytopenia, which manifests with symptoms and signs of anemia (decreased RBCs), clotting disorders (decreased platelets), and immunocompromise (decreased fully functional, mature WBCs). Patients with acute leukemia, especially those with AML, may develop extremely high WBC counts, increasing the risk of leukostasis and disseminated intravascular coagulation (DIC). Leukemic cells can also infiltrate extramedullary organs, resulting in hepatosplenomegaly, renal impairment, meningeal leukemia, and, less commonly, involvement of the skin and/or testicles. The first diagnostic steps include a complete blood count and peripheral blood smear to determine the patient's WBC count and assess for the presence of blasts. Bone marrow aspiration and biopsy are typically used to confirm the diagnosis, and subsequent cytogenetic analysis and immunophenotyping are used to identify subtypes and specific mutations. A chemotherapy regimen consisting of high-dose (induction) and low-dose (consolidation and maintenance) cycles is the mainstay of treatment. Additional measures, such as allogeneic stem cell transplantation, may be indicated in patients with poor prognostic factors (e.g., unfavorable cytogenetics) or if initial chemotherapy fails.
- Acute lymphoblastic leukemia 
- Acute myeloid leukemia 
Epidemiological data refers to the US, unless otherwise specified.
- No identifiable cause or risk factors in most cases
- Prior bone marrow damage due to alkylating chemotherapy or ionizing radiation
- Adult T-cell leukemia/lymphoma is linked to infection with . 
- Genetic or chromosomal factors
- No identifiable cause or risk factors in most cases
- Pre-existing hematopoietic disorder (most common identifiable cause) 
- Environmental factors 
- Genetic or chromosomal factors
- French-American-British (FAB) historical classification of ALL
- The current WHO Classification (2016) classifies ALL into subtypes of precursor lymphoblastic leukemia/lymphoma based on morphologic and genetic factors:
- Immunophenotype classification of ALL: based on the origin (B cell or T cell) and maturity of the leukemic cells
- The French-American-British (FAB) classification distinguishes between eight subtypes of AML, according to the histopathological appearance of the cells.
|FAB classification for AML|
|M0-AML||Acute myeloblastic leukemia without maturation|
|M1-AML||Acute myeloblastic leukemia with minimal granulocyte maturation|
|M2-AML||Acute myeloblastic leukemia with granulocyte maturation|
|M3-AML||Acute promyelocytic leukemia (APL)|
|M4-AML||Acute myelomonocytic leukemia|
|M5-AML||Acute monocytic leukemia|
|M6-AML||Acute erythroid leukemia|
|M7-AML||Acute megakaryoblastic leukemia|
- The WHO classification is based on various factors (e.g., presence of genetic abnormalities or associations to prior chemotherapy/radiation).
- Acquired somatic mutations (chromosomal translocations and other genetic abnormalities) in early hematopoietic precursors; → clonal proliferation of a lymphoid or myeloid stem cell line and arrest in cell differentiation and maturation in early stages of hematopoiesis; → rapid proliferation of abnormal and dysfunctional blasts (with impaired apoptosis pathways) → accumulation of leukemic white blood cells in the bone marrow → disrupted normal hematopoiesis → leukopenia (↑ risk of infections); , thrombocytopenia (↑ bleeding); , and anemia
- Immature blasts enter the bloodstream → infiltration of other organs (particularly the CNS, testes, liver, and skin)
|General features of acute leukemia|
|Clinical features of ALL||Clinical features of AML|
- Suspect acute leukemia in patients with suggestive clinical or laboratory features.
- Confirm the diagnosis with a morphological assessment.
- Further diagnostic studies: Immunophenotype, cytogenetics, and molecular genetic testing should be obtained in order to identify the subtype of acute leukemia.
In order to choose the best treatment strategy, the morphological assessment, immunophenotype, and genetic studies should be as comprehensive as possible.
Initial studies 
Routine laboratory studies
Findings on initial laboratory studies are usually nonspecific but may help to identify potentially life-threatening acute complications.
- Complete blood count and peripheral blood smear
- Liver chemistries and renal function tests: may be abnormal (e.g., secondary to disease infiltration)
Comprehensive metabolic panel and other metabolic studies
- Often abnormal due to increased cell lysis (see also “Tumor lysis syndrome”)
- Common findings include derangements of:
- Coagulation studies: Mild coagulopathy may be present. Studies may also help to identify features of DIC.
Confirmatory diagnostic tests 
|Histopathological features of acute leukemia|
Blasts (in bone marrow or peripheral blood) 
|Cell morphology || |
These studies are used to further characterize the cell line involved; some characteristics may be associated with a better response to certain therapies. These studies should be ordered in consultation with a specialist.
Immunophenotype and genetic studies 
|Immunophenotype and genetic studies in acute leukemias|
|Findings in ALL||Findings in AML|
|Genetic studies||Cytogenetics (karyotype, FISH)|
|Molecular testing (PCR) |
Myelogenous leukemias are myeloperoxidase positive.
Screening for extramedullary disease 
Consider the following studies to detect extramedullary disease based on the subtype of acute leukemia and clinical evaluation of the patient:
- CNS infiltration (common in ALL) 
- Testicular infiltration (relatively common in ALL): testicular ultrasound
- Thymic infiltration (primarily in T-cell ALL): Chest x-ray or CT chest may show a mediastinal mass.
- Hepatosplenic infiltration: Abdominal CT or ultrasound may show organ enlargement.
- Other forms of extramedullary disease: Consider PET-CT and/or lymph node biopsy.
The treatment of acute leukemia is decided by a hematologist-oncologist specialist depending on the specific subtype and results of molecular testing.
- Pretreatment: All patients should undergo a thorough evaluation, including baseline laboratory studies, ECG, and, if appropriate, a pregnancy test and an assessment for fertility preservation.
- Systemic chemotherapy: The regimen of choice is based on individual patient and disease factors.
- CNS infiltration (e.g., all patients with ALL). (commonly used): Consider adding for patients with or at high risk of
- Targeted chemotherapy: Consider adding for leukemias with specific immunophenotype and genetic profiles, e.g., Philadelphia translocation.
- Adjunctive treatment, e.g., radiation therapy, immunotherapy, or stem cell transplantation (SCT): Consider based on individual evaluation.
- Optimize nutrition and hydration.
- Manage chemotherapy-induced nausea and vomiting.
- Start general measures infection control measures.
- Provide psychosocial support as needed.
- Update recommended immunizations.
- Management of complications: : initiate monitoring, prevention, and early aggressive treatment as needed for infection, bleeding, pancytopenia, and oncologic emergencies (see “Management of complications”).
- Relapse or refractory leukemia: Consider re-induction chemotherapy, autologous SCT, or enrollment in a clinical trial in consultation with hematologist-oncologist.
Systemic chemotherapy 
- Induction therapy
- Consolidation therapy
- Low doses to maintain remission
- Average duration for an adult with ALL: 2–3 years
|Common agents used in chemotherapy regimens for acute leukemia |
If APL is suspected, start treatment early with a differentiation agent (e.g., ATRA) without waiting for immunotype or genetic confirmation. Treatment may be adjusted later depending on the results. 
In APL, the t(15;17) translocation and subsequent formation of the PML-RARA fusion gene can inhibit myeloblast differentiation under physiological levels of retinoic acid. High doses of ATRA (a vitamin A derivative) may induce myeloblast differentiation and promote remission.
Management of CNS infiltration 
- Intrathecal chemotherapy: administration of chemotherapeutic agents (e.g., triple therapy with methotrexate, cytarabine, and hydrocortisone) directly into the subarachnoid space via lumbar puncture or using an intraventricular catheter with a reservoir placed under the scalp
- CNS radiotherapy: Consider directed radiation therapy alongside intrathecal chemotherapy in select patients.
Intrathecal prophylaxis should be initiated early, as prevention of CNS leukemia is usually effective. Patients with CNS infiltration are at higher risk of relapse than those without CNS infiltration.
Advanced therapies 
Targeted therapy: Nonstandard chemotherapy or immunotherapy is indicated if certain mutations or markers are detected.
- Tyrosine kinase inhibitors (TKIs)
- Monoclonal antibodies: e.g., rituximab for CD20-positive Philadelphia chromosome-negative ALL, gemtuzumab ozogamicin for CD33-positive AML
- Chimeric antigen receptor T-cell therapy: may be used in ALL
- Autologous or allogeneic stem cell transplantation: Indications include patients with poor prognostic factors (e.g., unfavorable cytogenetics) and those who do not achieve remission with chemotherapy (see “Transplantation” for more information). 
Management of complications 
- Anemia: Transfuse pRBCs as needed on an individual basis.
- Thrombocytopenia: Consider prophylactic platelet to a target platelet count > 10,000/mm3 to prevent bleeding. 
- Neutropenia with fever or suspected infection: Start broad-spectrum IV antibiotics (see “Neutropenic fever” for details).
- Mucositis 
- Oncologic emergencies
- Specific chemotherapy toxicity
We list the most important complications. The selection is not exhaustive.
5-year survival rate following treatment
- ALL: The 5-year survival rate is generally higher compared to AML (varies from ∼ 20% in elderly patients to ∼ 80% in children and adolescents)
- AML: ∼ 30%, but it varies according to the patient's age. The survival time has increased more recently due to improvements in treatment.
Unfavorable prognostic factors
|Age|| || |
Favorable prognostic factors
To remember that translocation t(12;21) commonly manifests with pediatric B-ALL and usually has a favorable outcome, think: “Kids flip back to health!” (the number 12 is 21 flipped around).