acute myeloid leukemia

acute myeloid leukemia
Name	Acute Myeloid Leukemia
Synonyms	Acute myelogenous leukemia, acute non-lymphocytic leukemia (ANLL)
Caption	A peripheral blood smear showing blast cells, a hallmark of the disease.
Field	Hematology, Oncology
Symptoms	Fatigue, fever, bruising, shortness of breath
Complications	Severe infection, bleeding, leukostasis
Onset	Any age, most common in older adults
Duration	Rapid progression without treatment
Types	Classified by World Health Organization and French-American-British classification system
Causes	Genetic mutations in bone marrow cells
Risks	Smoking, previous chemotherapy, Down syndrome, myelodysplastic syndrome
Diagnosis	Blood test, bone marrow biopsy, flow cytometry
Differential	Acute lymphoblastic leukemia, myelodysplastic syndrome, aplastic anemia
Prevention	Not generally preventable
Treatment	Chemotherapy, stem cell transplantation, targeted therapy
Medication	Cytarabine, daunorubicin, midostaurin, venetoclax
Prognosis	Varies by subtype, age, and genetics
Frequency	~20,000 new cases annually in the United States
Deaths	~11,000 annually in the United States

acute myeloid leukemia is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and interfere with the production of normal blood cells. It is the most common acute leukemia in adults and represents a medical emergency requiring prompt diagnosis and treatment. The disease encompasses a heterogeneous group of malignancies with distinct genetic and clinical features.

Signs and symptoms

Common manifestations result from bone marrow failure and include fatigue and pallor due to anemia, fever and infection from neutropenia, and bruising or bleeding caused by thrombocytopenia. Patients may experience bone pain or tenderness, unintentional weight loss, and night sweats. The proliferation of leukemic cells can lead to leukostasis, presenting as shortness of breath, confusion, or visual changes, which is considered an oncologic emergency. Gingival hypertrophy and skin lesions known as leukemia cutis are specific findings in some subtypes.

Causes and risk factors

While most cases arise spontaneously, several environmental and genetic risk factors are established. Exposure to benzene and certain chemotherapy agents, particularly alkylating agents and topoisomerase II inhibitors, significantly increases risk. Ionizing radiation, such as from the atomic bombings of Hiroshima and Nagasaki, is a known causative agent. Genetic syndromes like Down syndrome, Fanconi anemia, and Bloom syndrome predispose individuals. Other risk factors include smoking, previous myelodysplastic syndrome, and certain myeloproliferative neoplasms like polycythemia vera.

Pathophysiology

The disease originates from a hematopoietic stem cell in the bone marrow that acquires a series of somatic mutations. These mutations, which may involve genes like FLT3, NPM1, and CEBPA, confer a proliferative advantage and impair cellular differentiation, leading to the accumulation of immature myeloblasts. These blast cells crowd out normal hematopoiesis, causing pancytopenia. The leukemic stem cell hypothesis posits that a small population of self-renewing cells drives the disease and contributes to relapse.

Diagnosis

Diagnosis requires a peripheral blood smear and a bone marrow biopsy to assess blast cell percentage and morphology. The defining criterion is the presence of 20% or more myeloblasts in the bone marrow or blood, as per World Health Organization criteria. Flow cytometry is essential for immunophenotyping, identifying markers like CD33 and CD13. Cytogenetic analysis and molecular genetics testing for mutations in genes like FLT3 and NPM1 are critical for classification and prognosis. Lumbar puncture may be performed to evaluate for central nervous system involvement.

Treatment

Initial therapy, termed induction chemotherapy, typically involves a regimen of cytarabine and an anthracycline like daunorubicin, aiming for complete remission. Consolidation therapy, often with high-dose cytarabine or allogeneic stem cell transplantation, is used to eliminate residual disease. Targeted therapy agents, such as midostaurin for FLT3 mutations and venetoclax combined with azacitidine, are now standard for specific subgroups. Gemtuzumab ozogamicin is an antibody-drug conjugate targeting CD33. Supportive care includes management of tumor lysis syndrome and prophylactic antimicrobial therapy.

Prognosis

Outcome varies widely based on patient age, cytogenetics, and molecular markers. Favorable-risk genetics include t(8;21) involving the RUNX1 gene and inv(16). Adverse features include mutations in TP53 and complex karyotype. The five-year survival rate is approximately 29% overall but is significantly lower in older adults. Allogeneic stem cell transplantation can be curative but carries risks of graft-versus-host disease and transplant-related mortality. Ongoing research by groups like the European LeukemiaNet refines prognostic models.

Category:Acute myeloid leukemia Category:Hematological malignancies Category:Medical emergencies