Acute adult leukemia

Acute leukemias in adults represent a heterogeneous group characterized by a monoclonal proliferation of immature hematopoietic cells invading the bone marrow, followed by the blood and other tissues.

There are three main forms based on the nature of the blast proliferation: myeloid (~70%), lymphoid (~20%), or biphenotypic (~10%). Their incidence is ~3 cases per 100,000 inhabitants per year, increasing with age (median age of onset: 65 to 70 years).

Etiologies and risk factors

Secondary leukemias

• Ionizing radiation and chemotherapy (++ alkylating agents [chlorambucil, cyclophosphamide, melphalan, …], topoisomerase inhibitors [etoposide = VP16, cisplatin, anthracyclines, …] within 5 to 7 years) anticancer treatments
• Myelodysplastic and myeloproliferative syndromes
• Genetic pathologies: trisomy 21, DNA repair anomalies (Fanconi, ataxia-telangiectasia, xeroderma pigmentosum, Bloom syndrome), congenital neutropenias, neurofibromatosis, Klinefelter syndrome

Secondary leukemias generally have a worse prognosis.

Suggestive clinical presentation

Bone marrow failure syndrome

• Signs of anemia: pallor, dyspnea, tachycardia, fatigue, dizziness, fainting spells, …
• Infectious signs: isolated fever, clinical foci poorly responsive to usual antibiotic therapy, ulcerative-necrotic sore throat, …
• Hemorrhagic signs: petechiae, epistaxis, spontaneous bruising/minor traumas, menorrhagia, gingival bleeding, bruising and bleeding at puncture sites (search for disseminated intravascular coagulation), …

Tumor syndrome

• Hypertrophy of hematopoietic organs: diffuse symmetrical and painless lymphadenopathy (small, often absent), splenomegaly and/or hepatomegaly
• Bone pain
• Gingival hypertrophy (++ acute leukemias with monocytic component)
• Leukostasis syndrome (++ acute leukemias with monocytic component): cyanosis, dyspnea, headaches, visual disturbances, tinnitus, neurological issues, consciousness disorders, priapism, … → therapeutic emergency.
• Localized tumors
• Infiltrative syndromes: blast meningitis, testicular infiltration, …

Moderate tumor syndrome with hematopoietic organ hypertrophy is more common in lymphoblastic leukemias.

Additional tests

Diagnostic:

• Biology:
  • Normochromic normocytic central anemia (90%) and central aregenerative anemia, thrombocytopenia (90%), leukopenia or hyperleukocytosis, presence of circulating blasts
• Bone marrow aspiration for myelogram (bone marrow biopsy in case of fibrosis or poor marrow)
  • Bone marrow with normal to increased cellularity (rarely poor)
  • > 20% blasts
    • Blasts positive for myeloperoxidase → Acute myeloblastic leukemia ++
    • Blasts negative for myeloperoxidase (<5% positive blasts) → Acute lymphoblastic leukemia ++
• Immunophenotyping
  • Gold standard for identifying the type of leukemia

In the context of pre-therapeutic assessment:

• Karyotype
• Molecular biology
• Evaluation of disease impact

Therapeutic management and prognosis

Treatment based on chemotherapy and corticosteroid therapy is the exclusive domain of specialists. The use of immunotherapies, still under study, is currently reserved in routine clinical practice for refractory cases in most countries.

Complete remission is achieved in ~70-80% of cases under treatment. The 5-year survival rate is ~30-40% (mortality related to disease, complications, and treatments). Cure is considered in the case of relapse-free survival at 5 years.

Bibliography

EMC, traité d'hématologie, Elsevier, 2018

Jameson JL et al., Harrison's Principles of Internal Medicine, 20th edition, McGraw Hill Higher Education, 2018