Acute Myeloid Leukemia

Acute myeloid leukaemia (AML) is clonal proliferation of myeloid blasts (20% or more in marrow or blood) with impaired normal haematopoiesis.

• Incidence 4 per 100,000 per year; median age 68; commonest acute leukaemia in adults.
• Risk factors: prior chemotherapy or radiotherapy, myelodysplasia, myeloproliferative neoplasms, benzene, smoking, Down syndrome, inherited syndromes.
• Genetic risk (ELN 2022): favourable (t(8;21) RUNX1::RUNX1T1, inv(16) CBFB::MYH11, NPM1 mutation without FLT3 ITD, biallelic CEBPA), intermediate, adverse (complex karyotype, TP53, KMT2A rearrangements, monosomy 7, ASXL1, RUNX1 mutations).
• APL (t(15;17) PML::RARA) is a medical emergency with coagulopathy, but highly curable.
• Complications: infection, bleeding, DIC, leukostasis, tumour lysis, differentiation syndrome.

• Fatigue, pallor, infections, fever, bleeding, bruising, bone pain, gum hypertrophy, skin infiltration (leukaemia cutis), chloroma.
• Leukostasis (WBC over 100 x 10^9/L): dyspnoea, confusion, visual disturbance.
• DIC in APL: haemorrhage, intracranial bleeding.
• Hepatosplenomegaly mild, lymphadenopathy uncommon.

• Full blood count and film (blasts, Auer rods), coagulation (fibrinogen, D dimer), LDH, uric acid, electrolytes, renal and liver tests.
• Bone marrow aspirate: 20% or more blasts, flow cytometry (CD13, CD33, CD34, CD117, MPO), cytogenetics, FISH, molecular panel (FLT3, NPM1, CEBPA, IDH1/2, TP53, KIT, RUNX1, ASXL1).
• Lumbar puncture for monocytic subtypes, high WBC, CNS symptoms.
• HLA typing early, cardiac function (echocardiography), infection screen, pregnancy test.
• Rapid PML::RARA testing and treat APL immediately on suspicion.

Fit patients, non APL

• Induction: cytarabine 100 to 200 mg/m2/day by continuous infusion for 7 days with daunorubicin 60 to 90 mg/m2 days 1 to 3 (7+3); add midostaurin 50 mg twice daily days 8 to 21 for FLT3 mutation (or quizartinib 35.4 mg daily for FLT3 ITD), gemtuzumab ozogamicin 3 mg/m2 for CBF-AML. CPX-351 for therapy related AML or MDS related changes.
• Consolidation: high dose cytarabine 1 to 3 g/m2 twice daily on days 1, 3, 5 for 3 to 4 cycles in favourable risk disease; allogeneic stem cell transplant in first remission for intermediate and adverse risk.
• Maintenance: oral azacitidine 300 mg days 1 to 14 for patients not proceeding to transplant; gilteritinib or sorafenib after transplant for FLT3.

Unfit or older

• Venetoclax 400 mg daily (ramp up over 3 days, dose adjust with azole) with azacitidine 75 mg/m2 days 1 to 7 (or decitabine, low dose cytarabine); median survival about 14 months.
• IDH inhibitors: ivosidenib 500 mg daily (IDH1), enasidenib 100 mg daily (IDH2); gilteritinib 120 mg daily for relapsed FLT3.

APL

• All trans retinoic acid 45 mg/m2/day with arsenic trioxide 0.15 mg/kg/day until remission, then consolidation (cure over 90%); idarubicin added in high risk. Start ATRA on suspicion, transfuse platelets to over 30 to 50 x 10^9/L, fibrinogen over 150 mg/dL.
• Differentiation syndrome: dexamethasone 10 mg twice daily, stop ATRA temporarily.

Supportive

• Hydration, allopurinol or rasburicase 0.2 mg/kg, hydroxyurea 2 to 3 g for leucostasis and leucapheresis.
• Antimicrobial prophylaxis (levofloxacin, posaconazole 300 mg daily, aciclovir), transfusions with irradiated products, central line care.
• Febrile neutropenia: piperacillin tazobactam 4.5 g every 6 hours.
• Minimal residual disease monitoring by PCR or flow.