- Clinical science
Acute leukemias are malignant neoplastic diseases that arise from either lymphoid (acute lymphoblastic/lymphocytic/lymphoid leukemia, or ALL) or myeloid (acute myeloid/myelogenous/myelocytic leukemia, or AML) cell lines. Acute leukemias are characterized by the proliferation of immature, non-functional cells in the bone marrow that are subsequently released into the bloodstream. ALL is the most common childhood malignancy, whereas AML mostly affects adults. Both diseases are associated with hereditary syndromes such as Down syndrome and previous exogenous bone marrow damage (e.g., caused by prior radiotherapy, chemotherapy, or exposure to benzene). The excessive proliferation of immature blasts in the bone marrow impairs all other cell lines, resulting in anemia, clotting disorders, and increased susceptibility to infections. Patients may also present with non-specific, flu-like symptoms or – in later stages – symptoms caused by leukemic organ infiltration (e.g., an enlarged scrotum). Diagnosis is usually confirmed by bone marrow aspirate, although a complete blood count and a peripheral blood smear are routinely performed as well. It is important to note that leukemias can present with a high, low, or even normal WBC count. Patients should be treated with a chemotherapy regimen consisting of high-dose (induction) and low-dose (consolidation and maintenance) cycles. Additional measures, such as allogeneic stem cell transplantation, may be indicated for patients with high-risk disease or if initial chemotherapy fails.
- Acute lymphoblastic leukemia
Acute myeloid leukemia
- Peak incidence: 65 years
- 80% of acute leukemias during adulthood are myelogenous
Epidemiological data refers to the US, unless otherwise specified.
- Origin and etiology mostly unknown
- Adult T-cell leukemia/lymphoma is linked to infection with HTL viruses.
- Genetic or chromosomal factors
- Environmental factors
- Genetic or chromosomal factors
- Myeloproliferative and myelodysplastic disorders
The French-American-British (FAB) classification distinguishes between eight subtypes of AML, according to the histopathological appearance of the cells. The WHO classification is based on various factors (e.g., presence of genetic abnormalities or prior chemotherapy/radiation):
|FAB classification for AML|
|M0||AML, minimally differentiated|
|M1||AML without maturation|
|M2||AML with granulocytic maturation|
|M3||Acute promyelocytic leukemia (APL)|
|M4||Acute myelomonocytic leukemia|
|M5||Acute monocytic leukemia|
|M6||Acute erythroid leukemias|
|M7||Acute megakaryoblastic leukemia|
The WHO classification relies on cytogenetic criteria to determine the immunophenotype of the leukemic cells. This includes their origin (B or T cell) and maturity:
- B-cell ALL (around 80–85% of cases)
- T-cell ALL (around 15–20% of cases)
The two-hit hypothesis assumes that leukemia is the result of two separate genetic mutations. The first causes clonal proliferation of a lymphoid or myeloid stem cell, while the second impairs its normal hematopoietic differentiation. As a result, the bone marrow is filled with numerous immature, non-functional cells that eventually impair normal hematopoiesis and cause the following abnormalities:
- Fatigue, pallor, and weakness (caused by anemia)
- Bleeding (petechiae, epistaxis, or hematoma, caused by thrombocytopenia)
- Hepatomegaly and/or splenomegaly (caused by leukemic infiltration)
- Headache, visual field changes, or other CNS symptoms (caused by CNS involvement)
- Fever (due to increased risk of infection)
- Leukemia cutis (or myeloid sarcoma): nodular skin lesions with a purple or gray-blue color
- Gingival hyperplasia (AML subtype M4 and M5)
- Painless lymphadenopathy
- Fever, night sweats, unexplained weight loss
- Bone pain
- Testicular enlargement (rare finding)
- Airway obstruction (stridor, difficulty breathing) caused by mediastinal infiltration
- leukemic meningitis) → headache, neck stiffness (or
The diagnostic workup usually includes clinical examination, CBC, peripheral blood smear, and a bone marrow aspirate or biopsy.
Complete blood count
Leukocytes: The white blood cell count (WBC) may be elevated, normal, or low and is not a reliable diagnostic marker.
- ALL: 50% may present with WBC count < 10,000/μL, 20% with WBC > 50,000/μL
- AML: 25–40% may present with WBC count < 5000/μL, 20% with WBC > 100,000/μL
- AML: Leukemic hiatus: A gap in the differentiation of white blood cells in which there is a high number of blast cells and mature leukocytes but no intermediate forms.
- Leukocytes: The white blood cell count (WBC) may be elevated, normal, or low and is not a reliable diagnostic marker.
- Peripheral blood smear: presence of blasts
- Increased cell lysis: ↑ LDH; and ↑ uric acid
- Bone marrow aspirate or biopsy: confirmatory diagnostic tests
|Myeloperoxidase (found in peroxidase-positive granules)||negative||positive|
|Terminal deoxynucleotidyl transferase (TdT)||positive||negative|
|Periodic acid-Schiff (PAS)||often positive||negative|
- Cerebrospinal fluid analysis: relevant for diagnosis and treatment of
- Chest x-ray: mediastinal widening in the case of thymic infiltration or mediastinal lymphadenopathy
- Abdominal ultrasound: organ enlargement (especially the liver and/or spleen)
Treatment involves aggressive chemotherapy and sometimes allogeneic transplantation. Depending on the type and stage of disease, additional measures such as radiation or targeted therapy may be considered.
Chemotherapy regimens are comprised of: induction → consolidation → maintenance therapy
Induction therapy (goal: massive reduction of tumor cell count)
- Duration: 4–6 weeks
- Effective, but can cause severe side effects
Re-induction therapy (goal: similar to induction therapy)
- Only indicated in case of relapse or failure of primary induction therapy
- Duration: 4–6 weeks
Consolidation therapy (goal: destruction of remaining tumor cells)
- Duration: several months
- Medium doses
Maintenance therapy (goal: maintaining remission)
- Duration: up to 24 months
- Low doses
The choice of drugs depends on the type of leukemia:
Preventive CNS treatment
- Intrathecal chemotherapy is indicated for all acute leukemia patients to prevent meningeal leukemia.
- CNS radiotherapy is not routinely used because it increases the risk of secondary malignancies, as well as endocrine (e.g., hypothyroidism, growth hormone deficiency) and neurocognitive (e.g., cognitive decline, neuroinflammation) side-effects.
Supportive therapy is very important as patients are severely immunocompromised.
- Pay special attention to personal hygiene (e.g., protective clothing)
- Provide a germ-free environment
- Avoid invasive procedures (catheterization, IV lines, unnecessary blood draws)
- Preventing infections
- Mucositis prophylaxis: local antimycotics
- Administering antibiotics as prophylaxis is controversial.
- In case of lymphopenia: PCP prophylaxis with TMP-SMX
- Herpes simplex prophylaxis with acyclovir may be necessary.
- Antiemetics: e.g., ondansetron
- Uric acid stone prophylaxis
- Description: The rapid destruction of tumor cells leads to a massive release of intracellular components, which subsequently damage the kidneys and may cause potentially life-threatening renal failure.
- Etiology: mostly occurs after initiating cytotoxic treatment of ALL, AML, or NHL
- Electrolyte changes
- All patients
- Possibly in addition to hydration
We list the most important complications. The selection is not exhaustive.
5-year survival rate
- ALL: The 5-year survival rate of treated patients varies from 20% (elderly patients) to 80% (children and adolescents).
- AML: The overall 5-year survival rate of treated patients is on average 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|| || |
|Leukocyte count|| |
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|Extent of disease|| |
Favorable prognostic factors
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