Acute Myeloid Leukaemia Flashcards
Acute myeloid leukaemia
Acute myeloid leukaemia occurs due to the malignant transformation and proliferation of myeloid progenitor cells.
Leukaemia refers to a group of malignancies that arise in the bone marrow. They are relatively rare but together are the 12th most common cancer in the UK, responsible for around 4,700 deaths a year.
There are four main types:
Acute myeloid leukaemia (AML)
Acute lymphoblastic leukaemia (ALL)
Chronic myeloid leukaemia (CML)
Chronic lymphocytic leukaemia (CLL)
Acute myeloid leukaemia
In AML proliferation of abnormal myeloid progenitor cells is seen. It refers to a heterogeneous group of conditions characterised by different genetic mutations.
Chemotherapy forms the mainstay of management in the form of induction and consolidation regimens with stem cell transplantation used in select patients.
Epidemiology of AML
There are approximately 3,200 cases of AML in the UK each year.
AML incidence
Incidence increases with age, becoming much more common in the over-60s with a median age at diagnosis of around 70.
The aetiology of AML is not completely understood.
The majority of patients present without clearly identifiable causative factors. However in some cases factors such as those described below are identified:
Myelodysplastic syndrome: MDS refers to a heterogenous group of blood disorders affecting haematopoiesis. These patients are at increased risk of developing AML, in particular those with high risk features (e.g. excessive blasts).
Congenital disorders: AML is seen more commonly in a number of congenital conditions including Down’s syndrome, congenital neutropaenia and Fanconi anaemia.
Radiation exposure: Is known to result in genetic damage with the rate of leukaemia increased in the survivors of the atomic blasts in Hiroshima and Nagasaki.
Previous administration of chemotherapy: Previous chemotherapy regimens, in particular alkylating agents and topoisomerase-II inhibitors, are associated with increased rates of AML.
Toxins: Exposure to certain toxins (e.g. benzene and organochlorine insecticides) have been shown to increase the risk of AML.
Pathogenesis
AML
AML occurs due to genetic changes in myeloid progenitor cells leading to a proliferating line of immature cells not responsive to normal control mechanisms.
There are complex group of genetic changes that can lead to AML including point mutations, translocations and gene silencing.
The abnormal proliferating cells result in reduced production of normal haematopoietic cell lines with abnormal cells accumulating in the bone marrow. This may be followed by spread and proliferation into other tissues.
AML often presents with signs of marrow failure or tissue infiltration.
Marrow failure
Anaemia:
Fatigue
Breathlessness
Angina
Neutropenia:
Recurrent infections
Thrombocytopenia:
Petechiae
Nose bleeds
Bruising
Tissue infiltration
The involvement and proliferation of lymphoid progenitors in body tissues is often clinically apparent at diagnosis:
Lymphadenopathy
Hepatosplenomegaly
Bone pain
Gum hypertrophy
Violaceous skin deposits
Testicular enlargement
Hepatomegaly and splenomegaly may cause symptoms such as early satiety or reduced appetite in …
Hepatomegaly and splenomegaly may cause symptoms such as early satiety or reduced appetite in leukaemia
Leucostasis
May occur due to large numbers of white cells entering the bloods stream. Organ dysfunction may result due to impairment of flow through small blood vessels. Features include:
Altered mental state
Headache
Breathlessness
Visual changes
… and … is required for formal diagnosis of AML.
Bone marrow aspirate and biopsy is required for formal diagnosis of AML.
What anaemia is common in AML?
A normocytic normochromic anaemia is common as is thrombocytopenia and reduced reticulocyte counts. The majority will have a raised white cell count, though leucopenia is commonly encountered. Circulating myeloblasts are seen in around 95% of patients.
Auur rods - classical finding on blood film in..
Blood smear should be completed in all patients. Auer rods - azurophilic structures seen in myeloid blasts - is the classical finding on peripheral blood film. They are also seen in myelodysplastic syndrome.
AML is defined based on bone marrow findings with a myeloid blast count of > …% (of 500 bone marrow cells).
AML is defined based on bone marrow findings with a myeloid blast count of > 20% (of 500 bone marrow cells).
Initial management - AML
Education and support: Patients (and their families) should be offered education and support for their diagnosis, normally co-ordinated by a specialist nurse.
Supportive care: Patients should be monitored for infections and coagulopathy and treated accordingly.
Cytoreduction: Should be considered in patients with signs of leukostasis and WBC > 100 × 109/L. This is typically achieved with hydroxycarbamide.
CNS involvement: Those with CNS involvement will normally be started on intrathecal chemotherapy (cytarabine).
Tumour lysis syndrome: Should be anticipated, prophylaxis should be given where indicated and appropriate medical services available (HDU/ITU) to offer organ support if significant TLS occurs.
