AML Flashcards
What
More common form of acute leukaemia in adults.
May be primary disease or follow a secondary transformation of a myeloproliferative disease.
Maturational arrest of bone marrow (BM) cells (blood cell precursors) in first stages of development.
Mechanism: activation of abnormal genes through chr. translocations and other genetic abnormalities -> reduced number of normal blood cells. Failure of apoptosis leads to accumulation in various organs, esp liver and spleen.
Genetically heterogeneous disease - can be classified into subgroups based on molecular genetic defect
Most subtypes show >30% blasts of a myeloid lineage in blood, BM or both.
Classification - WHO
1) AML with characteristic genetic abnormalities - ([t(8;21)], inversions in chr 16, [t(15;17)]. Higher rate of remission and better prognosis
2) AML with multilineage dysplasia - prior myelodysplastic syndrome (MDS) or myeloproliferative disease that transforms into AML. More often in elderly patients, worse prognosis.
3) AML and MDS, therapy-related - prior chemo/radiation and subsequently develop AML or MDS. May have specific chr abnormalities, worse prognosis.
4) AML, not otherwise catergorised.
Classification - French-American-British (FAB)
M0 - undifferentiated M1 - without maturation M2 - with granuloctic maturation M3 - acute promyelocytic M4 - granulocytic and monocytic maturation M5 - monocytic M6 - erythroleukaemia M7 - megakaryoblastic
Acute promyelocytic leukaemia M3
associated with [t(15;17)]
Fusion of PML and RAR-alpha genes
Presents younger than other types of AML (25yo)
Auer rods (seen with myeloperoxidase stain)
DIC or thrombocytopenia often at presentation
Good prognosis
Epidemiology/Risk factors
Most common acute leukaemia in adults
Incidence increases with age (median 67yo)
Most cases arise without apparent cause
Conditions that predispose include: MDSs, aplastic anaemia, myelofibrosis, paroxysmal nocturnal haemoglobinurea, polycythaemia rubra vera
Most patients with CML eventually develop a blast phase indistinguishable from AML
Congenital disorders that predispose (usually develop in childhood): Bloom’s syndrome, Down’s syndrome, congenital neutropenia, Fanconi’s anaemia, neurofibromatosis
Benzene exposure (via aplastic anaemia) Chemotherapy (via a myelodysplastic condition - 3-5 years; or 3-6 months, no myelodisplastic condition)
??irradiation - poor studies
Presentation - history
Symptoms may be due to bone marrow failure causing anaemia, neutropenia and thrombocytopenia or due to organ infiltration.
Children/young adults: acute symptoms over days to weeks.
Older people: fatigue over weeks or months; dizziness, SoBOE, angina/MI if CHD
Fever (WCC very high, neuts low), failure to respond to abx.
Bleeding (thrombocytopenia), coagulopathy (DIC), or both. Haemorrhage in lungs, GI and CNS can be fatal.
Fullness in LUQ and early satiety (splenomegaly)
Leukostasis -> respiratory distress and altered mental state (WCC extremely high (>100)). Medical emergency.
Bone pain
Presentation - signs
Pallor
Non-specific signs of infection, pneumonia
Most common sites of infiltration are liver, spleen and gums.
Hepatomegaly and splenomegaly
Gingivitis (swollen, bleeding gums)
Thrombocytopenia -> petechial; DIC may aggravate and cause larger lesions
Infiltration of skin -> leukaemia cutis (uncommon)
Investigations - bloods
FBC - anaemia, thrombocytopenia; WCC may be normal, high or low, sometimes extremely high, neutrophils are depleted and replaced with blast cells.
Clotting - DIC common (esp in M3), with prolonged PT, low levels of fibrinogen and fibrin degredation products present.
LDH: raised
Urate: may be raised due to rapid cell turnover
LFTs, U+Es: baseline before chemo; reduced K+, Ca2+ and Mg2+ in M4 and M5
If fever present, appropriate investigations and management of infection
Investigation - Specialist diagnostic tests
Bone marrow aspiration - DIAGNOSTIC
Must have >20% blasts in peripheral blood to diagnose AML.
If potentially suitable for BMT, HLA type them and family members, and do donor search
Cytochemical stains to classify M1 - M7 and flow cytometry to differentiate M0 and M7
Cytogenetic studies to subgroup - PROGNOSTIC INDICATOR - and differentiate t(15;17) (M3) - treated differently
Children: chromosomal analysis
Investigation - Imaging
ECG - chemo can be cardiotoxic
CXR - pneumonia or heart disease
Multiple-gated acquisition (MUGA) scan - chemo cardiotoxic
Management - criteria for response
Blast clearance in bone marrow to <5% of all nucleated cells
Morphologically normal haematopoiesis
Return of peripheral blood cell counts to normal levels
Management - conservative
Education
MDT
Management is coordinated in specialist centres
Management - chemo
Treatment usually in two phases - induction (to induce remission) and post-remission consolidation (intensification)
Number of different chemo agents used
Management - SCT
Stem cell transplant has significant relapse free and overall survival benefit for intermediate and high risk AML but not low risk in first complete remission
If no family donor, search international registry for HLA-matched unrelated donor
Management - M3 - acute promyelocytic leukaemia (APL)
All-trans retinoic acid (ATRA) and arsenic trioxide (ATO)
Usually in combo with other chemo
Supportive management, esp managing DIC and avoiding invasive procedures as much as possible are important.
