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