Acute Myeloid Leukemia

Present by :
Sumarti Fina Martha Wongso
Definition

• Malignant transformation of a myeloid precursor cell ;

usually occurs at a very early stage of myeloid development

All acute leukemias begin BEFORE clinical signs and symptoms occur
As the tumor volume expands, normal functional marrow cells decrease
Characterized by two major features
Ability to proliferate continuously
Due to mutations affecting growth factors
Transcription errors
Arrested development of normal cells
Lacks apoptosis
Etiology
Unknown In majority

Predisposing factors:
• Ionizing radiation exposure
• Previous chemotherapy : alkylating agents
• Occupational chemical exposure : benzene
• Genetic factors: Down’s Syndrome, Bloom’s, Fanconi’s Anemia
• Viral infection ( HTLV-1)
• Immunological : hypogammaglobulinemia
• Acquired hematological condition -Secondary
Epidemiology
• The incidence of AML is approximately 3.5 cases per 100,000 per year.
The median age at diagnosis is 67 years, and there is a slight male
predominance. The frequency of AML increases with age, with
approximately 6% of cases occurring in children and adults younger
than 20 years and more than 50% of cases occurring in patients 65
years of age and older.

• Rare in childhood & incidence increases with age

Clinical findings
General : Onset is abrupt & stormy
(usually present within 3 months)

• CLASSIC TRIAD
• Anemia
• Infection
• Bleeding/easy bruising/petechiae
• Fever
• Shortness of breath
• Fatigue
• Weight loss
• Pallor
• Bone pain & tenderness
Lab Features: Peripheral blood
 WBC count:
 variable at diagnosis
 ( 1-200 x 109/L)
 >20% blasts present
 Auer rods: fused primary granules in myeloblasts
 RBCs
 Decreased
 Hgb < 10g/dL
 Inclusions reflect rbc maturation defects
 Howell-Jolly, Pappenheimer, basophilic
stippling
 nRBCs present
 Platelets
 Decreased
 Hypogranular, giant forms
 Megakaryocyte fragments
Lab Features: MISC.
• BONE MARROW
• Hypercellular
• Decreased fat content
• >20 nonerythroid blasts
• Fibrosis

• MISC
• Hyperuricemic
• Increased LDH
WHO Classification of Acute Myelocytic Leukemias
 FAB Classification of Acute Leukemia
Morphology MPO SBB Specific esterase Nonspecific esterase PAS

M0 Acute myeloblastic >30% blasts Not present Not present Not present Not present Not present
leukemia: mimally No granules
differentiated

M1 Acute myeloblastic >30% blasts Present Present Can be Present Not present Not present
leukemia with no Few granules
maturation +/- Auer rods

M2 Acute myeloblastic >30% blasts Granules Present Present Can be Present Not present Not present
leukemia with common
maturation + Auer rods

M3 Acute promyelocytic >30% blasts Present Present Present Not present Not present
leukemia Prominent granules
++ Auer rods
Faggot cells

M4 Acute >30% blasts Present Present Present Present Not present

myelomonocytic >20%monocytes
leukemia + Auer rods

M4 eo Acute myelomonocytic >30% blasts Present Present Present Present Not present
leukemia >20%monocytes
With eosinophilia >5% abn eos
+ Auer rods

M5 Acute monoblastic >30% blasts>80% Can be Present Can be Present Can be Present Present Not present
leukemia with or monocytes
withour maturation with/without
differentiation

M6 Acute >30% myeloblasts Present: Present: Present: Not Present Present:

erythroleukemia >50% megaloblasts Myeloblasts Myeloblasts Myeloblasts Erythroblasts
+ Auer rods

M7 Acute megakaryocytic >30% Not present Not present Can be Present Not present/Present Not present
leukemia Megakaryoblasts
Cytoplasmic budding
Treatment and Management
• Approach “3 and 7”
• 3 days of 15-30 minute infusion of an anthracycline (idarubicin or
daunorubicin) or anthracenedione (mitoxantrone) combine with
100-200 mg/m2 of cytarabine (arabinosylcystosine; ara-C) as 24 hour
infusion daily for 7 days.

• Idarubicin: 12 mg/m2/d for 3 days

• Daunorubicin: 45-90 mg/m2/d for 3 days
• Mitoxantrone: 12 mg/m2/d for 3 days
Treatment and Management2
Supportive care :
• Anemia – red cell transfusion
• Thrombocytopenia – platelet concentrates
• Infection – broad spectrum IV antibiotics
• Hematopoietic growth factors : GM-CSF, G-CSF

• Metabolic problems :
• Monitoring hepatic / renal / hematologic function;
• Fluid & electrolyte balance, nutrition
• Hyperuricemia- hydration, Allopurinol

• Psychological support
Prognosis of all AMLs and therapy
• Death often occurs from infection and hemorrhage in weeks to
months unless therapy is started
• Median survival without treatment is 5 weeks
• 30% 5-yr survival in younger patients with chemotherapy
• Disease which relapses during treatment or soon after the end of
treatment has a poor prognosis
Thank you . . .