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Acute Myeloid Leukemia

Failure of cell maturation
Common age group. is 15 to 45 yrs.

Etiology

Heredity
    trisomy 21  (Down syndrome),  Inherited diseases with defective DNA repair, e.g., Fanconi anemia, Bloom syndrome, ataxia telangiectasia

Radiation - ionizing

Chemical and other occupational exposures
  •    Exposure to benzene, 
  •    Smoking and exposure to petroleum products, paint, herbicides, and pesticides, 

Drugs
  •     Alkylating agents
  •     Chloramphenicol, phenylbutazone, and, less commonly, chloroquine


French-American-British (FAB) Classification

M0: Minimally differentiated leukemia,5%
M1:Myeloblastic leukemia without     maturation,20%
M2: Myeloblastic leukemia with maturation,30%
M3: Hypergranular promyelocytic ,10%
M4: Myelomonocytic leukemia, 20%
M4Eo: Variant: Increase in abnormal marrow eosinophils
M5: Monocytic leukemia,10%
M6: Erythroleukemia (DiGuglielmo's disease), 4%
M7: Megakaryoblastic leukemia,1%

Clinical Presentation

Symptoms

Consequence of anemia, leukocytosis, leukopenia or leukocyte dysfunction, or thrombocytopenia. 3 months symptoms
fatigue or weakness, anorexia, weight loss, fever, Signs of abnormal hemostasis (bleeding, easy bruising) 
bone pain, lymphadenopathy, nonspecific cough, headache, or diaphoresis 

a mass lesion located in the soft tissues, breast, uterus, ovary, cranial or spinal dura, gastrointestinal tract, lung, mediastinum, prostate, bone, or other organs. 
The mass lesion represents a tumor of leukemic cells and is called a granulocytic sarcoma, or chloroma. 

Physical Findings

Fever, splenomegaly, hepatomegaly, lymphadenopathy, sternal tenderness, evidence of infection and hemorrhage  
GI bleeding, intrapulmonary hemorrhage, or intracranial hemorrhage  
Retinal hemorrhages, Infiltration of gingivae, skin, soft tissues, or the meninges with leukemic blasts at diagnosis is characteristic of the monocytic subtypes and those with 11q23 chromosomal abnormalities.  

Hematologic Findings

Severe  anemia : normocytic  normochromic
Decreased erythropoiesis often results in a reduced reticulocyte count,accelerated destruction of RBC. 
Active blood loss also contributes to the anemia.

Leukocytosis between 10,000 to 500,000 per cmm.
Leukemic cells in the blood 

Hyperuricemia
renal precipitation of uric acid and the nephropathy 
renal tubular dysfunction

Bone marrow findings

blasts are >20%
cytoplasm often contains primary (nonspecific) granules, and the nucleus shows fine, lacy chromatin with one or more nucleoli characteristic of immature cells.
Abnormal rod-shaped granules called Auer rods


Prognostic Factors

Advancing age is associated with a poorer prognosis,
Patients with t(15;17) have a very good prognosis (approximately 85% cured),

 with t(8;21) and inv(16) a good prognosis (approximately 50% cured

Treatment

Remission induction
    Standard therapy includes a 7-day continuous infusion of cytarabine and a 3-day course of daunorubicin or idarubicin with or without 3 days of etoposide.


Supportive Care

G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF)
Platelet transfusions to maintain a platelet count >20,000/L
RBC transfusions to maintain hemoglobin level >8 g/dL
Prophylactic antibiotics for infection contrl
 Oral nystatin or clotrimazole  to prevent localized candidiasis, acyclovir prophylaxis
Allopurinol – to prevent from tumor lysis syndrome
Consolidation
Patients who achieve complete remission undergo postremission consolidation therapy, including sequential courses of high-dose cytarabine, stem cell transplant (SCT),
Maintenance
prednisolone, vincristine, methotrexate and mercaptopurine

Patients with APL usually receive tretinoin together with anthracycline chemotherapy for remission induction and then consolidation chemotherapy (daunorubicin) followed by maintenance tretinoin, with or without chemotherapy.

Treatment of relapse
Once relapse has occurred, AML is generally curable only by SCT.