• Clinical science

Acute leukemia


Acute leukemia is a malignant neoplastic disease that arises from either the lymphoid cell line (acute lymphoblastic/lymphocytic/lymphoid leukemia, ALL) or the myeloid cell line (acute myeloid/myelogenous/myelocytic leukemia, AML). ALL is the most common childhood malignancy, whereas AML primarily affects adults. An underlying cause is rarely identifiable, but risk factors include prior chemotherapy and radiation therapy, as well as hereditary syndromes such as Down syndrome. AML is also associated with pre-existing hematologic disorders (e.g., myelodysplastic disorder, myeloproliferative disorders). Acute leukemias are characterized by the proliferation in the bone marrow of immature, nonfunctional white blood cells (“blasts”) that impair normal hematopoiesis and lead to pancytopenia manifesting with symptoms and signs of anemia (RBCs), clotting disorders (thrombocytes), and increased susceptibility to infection (↓ fully functional, mature WBCs). Leukemic cells also infiltrate extramedullary organs, resulting in hepatosplenomegaly and, less commonly, involvement of the skin, CNS, and/or scrotum. Patients with AML, in particular, may develop extremely high WBC counts, increasing the risk of leukostasis and DIC. The first diagnostic steps include a complete blood count and peripheral blood smear to determine the WBC count and the presence of blasts. Bone marrow biopsy or aspiration with subsequent cytogenetic analysis and immunophenotyping confirm the diagnosis. 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.


Epidemiological data refers to the US, unless otherwise specified.


Acute lymphoblastic leukemia (ALL)

Acute myeloid leukemia (AML)



ALL [1]

  • French-American-British (FAB) historical classification of ALL
    • L1 ALL with small cells (20–30%)
    • L2 ALL with heterogeneous large cells (70%)
    • L3 ALL with large cells, i.e., Burkitt lymphoma (1–2%)
  • The current WHO Classification (2016) classifies ALL into subtypes of precursor lymphoblastic leukemia/lymphoma based on morphologic and genetic factors:
    • B lymphoblastic leukemia with recurrent genetic abnormalities
      • ALL with BCR-ABL
      • ALL with t(v;11q23)
      • ALL with t(1;19)(q23;p13.3)
      • ALL with t(12;21)(p13;q22)
      • Hyperdiploid > 50
      • Hypodiploid
      • t(5;14)(q31;q32)
    • B lymphoblastic leukemia, not otherwise specified
    • Precursor T lymphoblastic leukemia/lymphoma
  • 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 Acute myeloblastic leukemia without maturation
M1 Acute myeloblastic leukemia with minimal granulocyte maturation
M2 Acute myeloblastic leukemia with granulocyte maturation
M3 Acute promyelocytic leukemia (APL)
M4 Acute myelomonocytic leukemia
M5 Acute monocytic leukemia
M6 Acute erythroid leukemia
M7 Acute megakaryoblastic leukemia
  • The WHO classification is based on various factors (e.g., presence of genetic abnormalities or associations to prior chemotherapy/radiation).
    • AML with recurrent genetic abnormalities (e.g., translocations)
    • AML with myelodysplasia-related changes
    • Therapy-related AML
    • AML not otherwise specified
    • Myeloid sarcoma
    • Myeloid leukemia associated with Down syndrome




Clinical features

Clinical features are either related to bone marrow failure, infiltration of organs by leukemic cells, or a combination of both.

General features of acute leukemia
Clinical features of ALL Clinical features of AML

Fever and lymphadenopathy are rare in AML, but can be common first signs in ALL!

Fever in a patient with acute leukemia must always be treated as a sign of infection until proven otherwise!

Remember metastasis for ALL by thinking of the following: ALL metaStaSizeS to the CNS and teSteS.




Laboratory studies

Bone marrow aspiration and biopsy

Morphology, histochemistry, cytogenetics, and immunophenotyping in ALL and AML
Morphology [20][21]
  • Large blasts (1.5–3 times the size of RBC)
  • Blasts with large, irregular nuclei (high nuclear-to-cytoplasm ratio)
  • Inconspicuous nucleoli
  • Coarse granules
  • No Auer rods
  • Large blasts (2–4 times the size of RBC)
  • Blasts with round or kidney-shaped nuclei, comparatively more cytoplasm than in ALL
  • Prominent nucleoli
  • Fine granules
  • Auer rods (present in 50% of cases) [22]
Histochemistry Myeloperoxidase (found in peroxidase-positive granules)
  • Negative
  • Positive
Terminal deoxynucleotidyl transferase (TdT)
  • Positive
  • Negative
Periodic acid-Schiff (PAS)
  • Often positive
  • Negative
Cytogenetics [16][9]
  • Philadelphia translocation (∼ 20–30% of ALL in adults and only 2–3% of ALL in children)
  • t(12;21): most common specific abnormality in childhood B-ALL
  • Hyperdiploidy is common in pre-B-ALL (see prognosis below)
Immunophenotyping by flow cytometry
  • The majority of subtypes are positive for CD13, 33, 34, 117, and HLA-DR.

Myelogenous leukemia is myeloperoxidase positive.

Further tests




  • Aggressive chemotherapy is the mainstay of treatment; prognosis is good with treatment.
  • Radiation and/or targeted therapy are considered depending on the type and stage of disease.
  • Allogeneic stem cell transplantation is indicated in patients with poor prognostic factors or who do not achieve remission with chemotherapy.
  • Supportive measures are vital to manage severely immunocompromised patients and prevent treatment-related complications.


Chemotherapy regimens are comprised of induction, followed by consolidation, and finally maintenance therapy. The choice of chemotherapeutic agents is based on the cytogenetics of the leukemic cells. [21]

  1. Induction therapy (goal: massive reduction of tumor cell count)
    • Duration: 4–6 weeks
    • High-dose chemotherapy regimens are effective but usually cause severe side effects.
  2. Re-induction therapy (goal: massive reduction of tumor cell count)
    • Only indicated in case of relapse or failure of primary induction therapy
    • Duration: 4–6 weeks
  3. Consolidation therapy (goal: destruction of remaining tumor cells)
    • Begin after complete remission is achieved
    • Duration: several months
    • Medium doses
    • ALL regimen: variable drug regimens
  4. Maintenance therapy (goal: maintaining remission)
Common agents used in the initial treatment of acute leukemia
ALL [27][28] AML
Standard regimen
Philadelphia translocation

85% of children with ALL achieve complete remission with chemotherapy! [21]

A t(15;17) translocation causes the retinoic acid receptor to change, preventing myeloblast differentiation from occurring under physiologic levels of retinoic acid. Thus, high doses of all-trans-retinoic acid (vitamin A) may induce remission by causing malignant cells to mature.

Preventive CNS treatment [29][14][30][31][32][33]

Allogeneic stem cell transplantation

  • Indication: poor prognostic factors (e.g., unfavorable cytogenetics); or patients who do not achieve remission through chemotherapy

Supportive therapy [12][21]



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

  • < 1 year or > 10 years

  • > 60 years
Disease features
  • WBC count > 50,000/mm3
  • CNS involvement at diagnosis
  • Various translocations, e.g., t(6;9)
  • Karyotype abnormalities (e.g., trisomy 8, monosomy 5 or 7)
  • FLT3 gene mutation
  • Complex pattern of aberrations (i.e., > 3 aberrations)

Favorable prognostic factors

  • < 50,000/mm3
  • No CNS involvement
  • t(12;21)
  • Hyperploidy

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).