Acute Myeloid Leukaemia (AML)

Table Of Contents
  1. Acute Myeloid Leukaemia

Acute Myeloid Leukaemia

Acute myeloid leukaemia is an acute leukaemia that involves myeloid cell line precursors. The presence of granules in the cells is a characteristic feature of AML.

The incidence of AML increases with age. It peaks at around 70 years of age.

  • WHO classification of AML (based on clinical manifestation, morphology, immunophenotyping and genetic features)
    • AML with recurrent genetic abnormalities
    • AML with myelodysplasia-related features (Monosomy 5, Monosomy 7 – poor prognosis)
    • Therapy-related AML, e.g. history of alkylating agent use
    • AML, not otherwise specified (Classified further using FAB)
    • Myeloid Sarcoma
    • Myeloid proliferations related to Down Syndrome (Trisomy 21)
  • French-American-British (FAB) classification of AML (based on the lineage affected and level of association)
    • AML with minimal differentiation (AML-M0)
    • AML without maturation (AML-M1)
    • AML with maturation (AML-M2)
    • Acute Promyelocytic Leukemia (AML-M3)
    • Acute Myelomonocytic Leukemia (AML-M4)
    • Acute Monoblastic and Monocytic leukemia (AML-M5)
    • Pure Erythroid Leukemia (AML-M6)
    • Acute Megakaryoblastic Leukemia (AML-M7)
  • Causes
    • Chromosomal abnormalities
      • t(8:12)
      • t(15:17) APL
      • t(16:16) inverted 16
      • Trisomy 21 (Down syndrome)
      • MDS-associated mutations that transform into AML: Monosomy 5, Monosomy 7, and del(5q)
    • Environmental exposure
      • Ionizing radiation
      • Chemotherapeutic agents – alkylating agents
      • Occupational agents – benzene
    • Drugs (therapy-related AML)
      • Alkylating agents
      • Topoisomerase II inhibitors
      • Epipodophyllotoxins
      • Anthracyclines
      • Mitoxantrone
  • Pathogenesis of AML
    • AML involves precursor cells committed to the myeloid line
    • Accumulation of genetic mutations (first and second hit) → clonal proliferation of myeloid precursors and maturation arrest → accumulation of immature blasts in the bone marrow and invasion of organs → bone marrow failure, organomegaly, and myeloid sarcoma
  • Signs and symptoms
    • Recurrent infections and fever due to neutropenia
    • Bleeding due to thrombocytopaenia
    • Symptoms of anaemia
    • Bone pain
    • Lymphadenopathy
    • Hepatosplenomegaly due to extramedullary hematopoiesis
    • Orbital swelling due to myeloid sarcoma
    • Headache
    • Lethargy
    • Mental status changes and focal neurological deficits when there is CNS involvement
  • Differentials
  • Investigations
    • Complete blood count
      • Anemia and thrombocytopenia
      • Decreased, normal or increased WBC
    • Peripheral blood film
      • Myeloblasts present
      • Large nuclei
      • Prominent nucleoli
      • Variable amount of pale blue cytoplasm
      • Auer rods and granules
    • Bone marrow aspirate
      • 20% blasts in the Bone marrow for diagnosis
    • Bone marrow Biopsy to rule out metastases, assess cellularity, and presence of fibrosis (dry tap)
    • Phenotyping using cytochemical stains
      • Myeloperoxidase (MPO) is positive for myeloblasts
      • Nonspecific Esterase (NSE) positive for Monoblasts and monocytes
      • Specific Esterase (CAE) positive for the granulocytic lineage
      • Periodic Acid Schiff positive in erythroblasts and megakaryoblastic lineages (diffuse positivity)
      • Sudan Black Stain positive for granulated blasts
    • Flow cytometry (Immunophenotyping)
      • AML: CD11b, CD34, CD33, CD45, CD64, CD65, CD117, MPO, Lysozyme
      • Pure Erythroid Leukemia (AML-M6): CD71, Glycophorin A positive
      • Acute Megakaryoblastic Leukemia (AML-M7): CD41, CD61 positive
    • Cytogenetics (karyotyping and FISH)
      • Good prognosis: t(8;12), inv(16), t(16:16), t(15;17),
      • Poor prognosis: MDS-associated mutations (Monosomy 5, Monosomy 7, del(5q)), t(11:var) associated with therapy-induced AML
    • Polymerase chain reaction
      • Nucleophosmin mutation (NPM1), CEBPA, FLT3/ITD, c-KIT, WT1, PML-RARA
    • Lumbar Puncture and CSF analysis for all patients with AML + neurological symptoms
    • Serum biochemistries to evaluate for Tumour Lysis Syndrome
  • Treatment
    • Psychological support
    • Nutritional support
    • Reverse isolation during admission
    • Transfusion
    • Broad-spectrum antibiotics, if indicated
    • Immunisation
    • Chemotherapy
      • Standard induction with Idarubicin and Cytarabine (IAC)
      • Intrathecal Cytarabine if there is CNS involvement
      • ATRA and Arsenic trioxide for AML-M3
    • Haematopoietic cell transplant for patients with unfavourable cytogenetics
  • Complications
    • Leukostasis – dyspnea, chest pain, headaches, altered mental status, cranial nerve palsies, and priapism
    • Chemotherapy-related complications
      • ARA-C (Cytarabine) → multiple complications
      • Idarubicine → Dilated cardiomyopathy
    • Tumour lysis syndrome
    • Disseminated intravascular coagulopathy – particularly with AML-M3
    • Complications related to cytopenias

Acute Promyelocytic Leukaemia (APL or AML-M3)

Acute promyelocytic leukaemia (AML-M3) is a rare subtype of AML that is characterised by arrested maturation at the promyelocytic stage, and the classic chromosome translocation t(15:17), which forms the PML-RARA fusion protein. Malignant cells in AML-M3 have granules and Auer-rods.

  • Treatment
    • ATRA (ALL-trans retinoic acid) and arsenic trioxide to induce maturation of immature malignant cells
  • Complications
    • Disseminated Intravascular Coagulation- auer rods activate platelets

Down Syndrome and Acute Megakaryoblastic Leukaemia (AML-M7)

  • Children with Down Syndrome have a 10 to 20 times greater risk of developing AML.
  • The additional chromosome 21 is an important predisposing factor for the development of AML.
  • AML in children with Down Syndrome has a unique biological characteristic that greatly influences therapy and prognosis.

Chloromas (Myeloid Sarcomas)

Myeloid sarcomas are extramedullary deposits of myeloid blasts, leading to destruction or compression of normal tissue.

  • Sites of chloromas
    • Central nervous system
    • Skin
    • Orbit
    • Bone
  • Risk factors for developing chloromas
    • Younger age
    • High WBC at diagnosis
    • t(8:21)
    • AML-M4
    • AML-M5
Reference Intervals ›
Biochemistry
ACTHP: <80 ng/L
ALTP: 5–35 U/L
AlbuminP: 35–50 g/L
AldosteroneP: 100–500 pmol/L
Alk. phosphataseP: 30–130 U/L
α-AmylaseP: 0–180 IU/dL
α-FetoproteinS: <10 kU/L
Angiotensin IIP: 5–35 pmol/L
ADHP: 0.9–4.6 pmol/L
ASTP: 5–35 U/L
BicarbonateP: 24–30 mmol/L
BilirubinP: 3–17 μmol/L
BNPP: <50 ng/L
CRPP: <10 mg/L
CalcitoninP: <0.1 mcg/L
Calcium (ionized)P: 1.0–1.25 mmol/L
Calcium (total)P: 2.12–2.60 mmol/L
ChlorideP: 95–105 mmol/L
CholesterolP: <5.0 mmol/L
VLDLP: 0.128–0.645 mmol/L
LDLP: <2.0 mmol/L
HDLP: 0.9–1.93 mmol/L
Cortisol AMP: 450–700 nmol/L
Cortisol MidnightP: 80–280 nmol/L
CK ♂P: 25–195 U/L
CK ♀P: 25–170 U/L
CreatinineP: 70–100 μmol/L
FerritinP: 12–200 mcg/L
FolateS: 2.1 mcg/L
FSHP: 2–8 U/L ♂; >25 menopause
GGT ♂P: 11–51 U/L
GGT ♀P: 7–33 U/L
Glucose (fasting)P: 3.5–5.5 mmol/L
Growth hormoneP: <20 mu/L
HbA1C (DCCT)B: 4–6%
HbA1C (IFCC)B: 20–42 mmol/mol
Iron ♂S: 14–31 μmol/L
Iron ♀S: 11–30 μmol/L
Lactate (venous)P: 0.6–2.4 mmol/L
Lactate (arterial)P: 0.6–1.8 mmol/L
LDHP: 70–250 U/L
LHP: 3–16 U/L
MagnesiumP: 0.75–1.05 mmol/L
OsmolalityP: 278–305 mosmol/kg
PTHP: 0.8–8.5 pmol/L
PotassiumP: 3.5–5.3 mmol/L
Prolactin ♂P: <450 U/L
Prolactin ♀P: <600 U/L
PSAP: 0–4 mcg/mL
Protein (total)P: 60–80 g/L
Red cell folateB: 0.36–1.44 μmol/L
Renin (erect)P: 2.8–4.5 pmol/mL/h
Renin (recumbent)P: 1.1–2.7 pmol/mL/h
SodiumP: 135–145 mmol/L
TBGP: 7–17 mg/L
TSHP: 0.5–4.2 mU/L
T4P: 70–140 nmol/L
Free T4P: 9–22 pmol/L
TIBCS: 54–75 μmol/L
TriglyceridesP: 0.50–2.3 mmol/L
T3P: 1.2–3.0 nmol/L
Troponin TP: <0.1 mcg/L
Urate ♂P: 210–480 μmol/L
Urate ♀P: 150–390 μmol/L
UreaP: 2.5–6.7 mmol/L
Vitamin B12S: 0.13–0.68 nmol/L
Vitamin DS: 50 nmol/L
Arterial Blood Gases
pH7.35–7.45
PaCO₂4.7–6.0 kPa
PaO₂>10.6 kPa
Base excess±2 mmol/L
Urine
Cortisol (free)<280 nmol/24h
Hydroxyindole acetic acid16–73 μmol/24h
Hydroxymethylmandelic acid16–48 μmol/24h
Metanephrines0.03–0.69 μmol/mmol cr.
Osmolality350–1000 mosmol/kg
17-Oxogenic steroids ♂28–30 μmol/24h
17-Oxogenic steroids ♀21–66 μmol/24h
17-Oxosteroids ♂17–76 μmol/24h
17-Oxosteroids ♀14–59 μmol/24h
Phosphate (inorganic)15–50 mmol/24h
Potassium14–120 mmol/24h
Protein<150 mg/24h
Protein/creatinine ratio<3 mg/mmol
Sodium100–250 mmol/24h
Haematology
WCC4.0–11.0 ×10⁹/L
RBC ♂4.5–6.5 ×10¹²/L
RBC ♀3.9–5.6 ×10¹²/L
Hb ♂130–180 g/L
Hb ♀115–160 g/L
PCV ♂0.4–0.54 L/L
PCV ♀0.37–0.47 L/L
MCV76–96 fL
MCH27–32 pg
MCHC300–360 g/L
RDW11.6–14.6%
Neutrophils2.0–7.5 ×10⁹/L (40–75%)
Lymphocytes1.0–4.5 ×10⁹/L (20–45%)
Eosinophils0.04–0.44 ×10⁹/L (1–6%)
Basophils0–0.10 ×10⁹/L (0–1%)
Monocytes0.2–0.8 ×10⁹/L (2–10%)
Platelets150–400 ×10⁹/L
Reticulocytes0.8–2.0% / 25–100 ×10⁹/L
Prothrombin time10–14 s
APTT35–45 s
Paediatric
Pulse Rate (bpm)
Neonate140–160
Infant <1yr120–140
1–5 years110–130
5–12 years80–120
>12 years70–100
Respiratory Rate (tachypnoea)
0–2 months≥60/min
2–12 months≥50/min
1–5 years≥40/min
>5 years≥30/min
Blood Pressure (mmHg)
Term65/45
1 year75/50
4 years85/60
8 years95/65
10 years100/70
Weight Formulas
3–12 months(a + 9)/2 kg
1–6 years2a + 8 kg
>6 years(7a − 5)/2 kg
Haemoglobin (g/dL)
Term newborn13–20
1 month11–18
2 months10–15
1–2 years10–13
>2 years11–14
MUAC (6 months–5 years)
Obese>17.5 cm
Normal13.5–17.4 cm
At risk12.5–13.4 cm
Moderate malnutrition11.5–12.4 cm
Severe malnutrition<11.5 cm
Developmental Milestones
Social smile1.5 months
Head control4 months
Sits unsupported7 months
Crawls10 months
Stands unsupported10–12 months
Walks12–13 months
Talks18 months
CSF WBC (/mm³)
Term newborn0–25
>2 weeks0–5
Calculator ›

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