Acute Myeloid Leukemia

Dr Alex Mogere
Consultant physician
defn
• Clonal expansion of myeloid precursor cells with reduced capacity to
differentiate
• There is accumulation of abn blast cells in BM
• There is impaired prdn of normal blood cells
Aetiology
• No single agent/mostly a combination
• Genetic predisposition:
-Downs Syndrome
-fanconi anemia
-Bloom syndrome
-Klinefelter syndrome
-Turner syndrome
-neurofibromatosis
Cont. aetiology
• Environmental factors:
-Chemical agents eg benzene
-Chemotherapeutic agents topoisomerase inhibitors, alkylating agents
-Radiation
-Immunological deficiencies
-smoking
Epidemiology
• Commoner in men than women
• Median age of onset is about 70 yrs
• Commoner in developed world
• Commoner in whites
Clinical presentation
• neutropenia-fever, chills
• Thrombocytopenia-bleeding, bruising
• anemia,-fatigue
• Leucostasis- pulmonary,cns etc presentations
p/e
• Retinal hemorrhages
• Bone tenderness
• Gum hypertrophy
• Pallor, petechial
• Cns manifestations –esp m4,m5
• Extramedullary disease eg sarcoma
• Hepatomegaly
• splenomegaly
Gum hypertrophy
DDX
• Aplastic anemia
• ALL
• MDS
• B-cell lymphoma
• Anemia
• BMF
• CML
• Primary myelofibrosis
• B-cell lymphoma
Lab invxs
• CBC,PBF
• BMA,biopsy,cytogenetics, molecular analysis
• Immunohistochemistry
• HLA typing
• Evaluate myocardium before chemotx
DX
• WHO-20% or more of blast cells on BMA
• Certain cryptogenic abnormalities regardless of blast status
• T(8,21),(q22;q22)
• Inversion 16(P13q22)
• t (16;16) (p13;q22)
• t(15;77)(q22;q12)
WHO classification
leucostasis
• Found predominantly in those with wbc of >100,000
• CNS symptoms- headaches, visual changes etc
• RS-dyspnea, chest pain
• Others-renal insufficiency, MI, priapism
Leucostasis tx
• Adequate hydration
• Leukapheresis
• Induction chemotx or high dose hydroxyurea
• Don’t do blood transfusion—increased blood viscosity
• Monitor for Tumor lysis syndrome or DIC
Tumor lysis syndrome(TLS)
• X-terized by massive release of cellular components following
malignant cells breakdown
• Esp seen in malignancies with high proliferation rates-ALL, BL, AML
• Risk factors –preexisting hyperuricemia, renal insufficiency,
hypovolemia
• Labs- high K+, PO4,UA, low Ca2+, renal insufficiency, metabolic
acidosis
TLS-Clinical presentation
• hyperCa2+- tetany, cramps, hypotension, arrhythmia
• High K+- arrhythmia, paraesthesia, cramps
• High PO4- nausea, vomiting,diaarhoea, seizures,lethargy
• High UA- crystallization of UA in renal tubules,leading to RI
TLS TX
• Aggressive fluids-iv
• Hypouricemic agents: allopurinol(Inhibits XO),
Rasburicase(recombinant urate oxidase,not to be given to Pg, and
G6PD def),
• Dialysis in severe cases
DIC
• Anemia, infections
• Bleeding diathesis
• Migratory thrombophlebitis*(trousseaus syndrome)
• Endocarditis(non bacterial thrombotic/marantic)
• DVT/PE
• LABS –prolonged PTI/INR,PTT, microangiopathic anemia(schistocytes),
• High D-dimer
• Thrombocytopenia
• Low fibrinogen
• High fibrin degradation products
DIC TX
• Supportive
-Platelets
-Cryoppt
-FFP
• TX obvious thrombosis-UFH,lmwh, often resistant to
warfarin,Activated protein C
• Tx underlying malignancy
AML TX: complete remission
• Plt count > 100000
• Neutrophil count > 1000
• BM with \<5% blasts
• Molecular complete remission– using PCR, flow cytometry
Remission induction tx
• Anthracycline (daunorubicin,idarubicin) and cytarabine regimen(3+7
regimen)
• Obtain BM biopsy 7-10/7 after completion of tx
• If remission unachieved repeat induction regime

• Idarubicin: 12mg/m2/dx 3 days(15-20 min infusion)

• Or daunorubicin: 45-90 mg/m2/dx 3 days
• Cytarabine: 100-200mg/m2 x 24hr infusion daily for 7 days
Ct tx
• These regimens require adequate cardiac, hepatic and renal fxn
evaluation
• Favourable risk– high dose cytarabine 3-4 cycles
• Intermediate and adverse risk-stem cell transplant
HSCT(PT <60YRS); NCCN
• HSCT is an option under the following conds
• After induction failure with std-dose or high dose cytarabine
• In significant residual disease without a hypocellular marrow, after a
high dose cytarabine induction
• Post- remission tx in in intermediate/poor risk cytogenetics/and or
molecular abnormalities
Targeted tx
• Gemtuzumab ozogamicin- pts expressingCD33
• IDH1 mutated AML-ivosidenib
• IDH2 muated AML- Enasidenib
APL(AML-M3) TX
• Special subtype of AML
• Pts are on average < 40yrs(median age)
• Mostly present with pancytopenia rather than high WBC
• Most commonly associated with coagulopathy/DIC, fibrinolysis
• Platelet transfusion to maintain platelets to at least 30,000
• Cryoppt if fibrinogen level < 100mg/dl
• 2 histologic types-hypergranular/hypogranular
• t(15;17) or PML/RARA rearrangement respond well to ATRA &
chemotx
CONT .APL TX
• Pts with APL should begin with at least ATRA immediately
• Then stratify according to risk—low risk: wbc < 10x10^9/l

• Low risk: ATRA 45mg/m2/d in 2 divided doses + arsenic trioxide -

0.15mg/kg/d until bone barrow remission
• Other alternatives-ATRA/DAUNORUBICIN/CYTARABINE combination or
ATRA/IDARUBICIN combo
• Consolidation ATRA+arsenic trioxide x 4 weeks out of 8 weeks x 4 cycles,
then ATRA X 2 weeks on, 2 weeks off for 7 cycles
• High risk: ATRA+ chemotx with or w/o arsenic trioxide
THANK YOU!