Acute Myeloid Leukaemia (AML) Flashcards
what is acute myeloid leukaemia (AML)?
a malignant clonal disorder of hematopoietic stem cells characterised by uncontrolled proliferation, accumulation, and impaired differentiation of myeloid precursor cells (e.g. myeloblasts) in the bone marrow, peripheral blood, and sometimes other tissues
what is the pathophysiology of AML?
- arises from the uncontrolled growth of the myeloid cell line in the bone marrow, leads to a proliferation of immature, non-functional white blood cells, known as ‘blasts’
- these blasts disrupt normal haematopoiesis, which can cause pancytopenia
- immature blast cells may enter the bloodstream and infiltrate other organs (e.g. the CNS, liver, and skin)
what are the risk factors for AML?
- pre-existing haematological disorders (e.g. myelodysplastic syndrome (MDS), myeloproliferative disorders (MPD), aplastic anaemia, paroxysmal nocturnal haemoglobinuria (PNH))
- congenital disorders (e.g. down’s syndrome, bloom syndrome)
- environmental exposure (e.g. chemotherapy, radiation, tobacco smoke, benzene)
what are the symptoms of AML?
- may be asymptomatic
- may be present for only days to weeks before diagnosis
- anaemia (e.g. fatigue, weakness, pallor, malaise, palpitations, dyspnoea, tachycardia, and exertional chest pain)
- thrombocytopenia (e.g. mucosal bleeding, easy bruising, petechiae/purpura, epistaxis, bleeding gums, and heavy menstrual bleeding)
- neutropenia (e.g. increased susceptibility to infections)
- leukaemic infiltration (e.g. abdominal discomfort/fullness may be present due to hepatosplenomegaly)
what may the findings on examination be in AML?
- weight loss
- anaemia (e.g. pallor, cardiac flow murmur)
- fever
- thrombocytopenia (e.g. petechiae, dermal bleeding, ecchymoses)
- leukaemic infiltration (e.g. hepatosplenomegaly, lymphadenopathy, swollen gums)
what may less commonly be found on examination of AML in later stages of the disease?
- leukaemia cutis (e.g. infiltration of the skin with leukaemia cells)
- leukostasis (e.g. ARDS, altered mental status)
what are the investigations for AML?
- FBC
- blood film
- LDH
- uric acid
- coagulation
- bone marrow biopsy
- flow cytometry
what might a peripheral blood smear show in AML?
- myeloblasts (e.g. immature cells with large nuclei, usually with prominent nucleoli)
- auer roads (e.g. appear as pink/red rod-like granular structures in the cytoplasm and are myeloperoxidase positive)
what is the difference between bone marrow aspiration and bone marrow trephine biopsy?
- an aspirate is when a syringe of liquid bone marrow is filled
- a trephine is when a 1-2cm piece of core bone marrow is removed in one piece
what analysis is typically performed on the bone marrow of a patient with AML?
- immunophenotyping (e.g. by flow cytometry)
- cytogenetics (e.g. a study of chromosomal structure, location, and function in cells)
- FISH (e.g. a laboratory technique for detecting and locating a specific DNA sequence on a chromosome)
how is flow cytometry used in the diagnosis of AML?
- flow cytometry may be performed with peripheral blood or marrow aspirate
- used to identify circulating myeloblasts by characteristic patterns of surface antigen expression (e.g. CD34, HLA-DR, CD117, CD13, and CD33)
how is acute myeloid leukaemia (AML) classified?
- world health organisation (WHO) classification
- french-american-british (FAB) classification
what are the phases of chemotherapy in the treatment of AML?
- induction
- consolidation
- maintenance
what is the purpose of induction chemotherapy in AML, and how long does it typically last?
- a shorter and more intensive period of treatment that can last from 2-6 weeks
- to clear the blood of leukemic cells (blasts) and to reduce the number of blasts in the bone marrow to a normal level
what is the purpose of consolidation chemotherapy in AML, and when is it given?
- given once a patient has recovered from the induction phase
- the aim of consolidation is to kill the remaining blast cells
- is indicated even if there is no evidence of tumour cells remaining after induction
what is the purpose of maintenance chemotherapy in AML?
- involves administering a low dose of chemotherapy regularly to maintain remission
- can last from months up to 2 years
what are common chemotherapeutic agents used in the treatment of AML?
- cytarabine (cytosine arabinoside – ara-C) (e.g. an anti-metabolite)
- daunorubicin (daunomycin) or idarubicin (e.g. an anthracycline)
- all-trans retinoic acid (ATRA) and arsenic are more commonly used in the treatment of acute promyelocytic leukaemia (APML)
what is a bone marrow transplant in AML, and where do the stem cells typically come from?
- hematopoietic stem cell transplant
- usually allogenic transplants where stem cells come from another person, called a donor
- the donor’s stem cells are given to the patient after the patient has chemotherapy and/or radiation therapy
when is a bone marrow transplant typically indicated in AML patients?
- high cytogenetic risks
- lack of complete remission after first induction treatment
- high initial leukocyte count
what supportive therapies are used in the treatment of AML?
- blood cell transfusions (e.g. platelet transfusions are performed when platelets fall below < 10 × 109/L, red cell transfusions are performed when haemoglobin is < 7 or 8 g/dL)
- oral hygiene (e.g. mycostatin, chlorhexidine mouthwash)
- antimicrobial prophylaxis (e.g. co-trimoxazole, valacyclovir)
- allopurinol (e.g. TLS)
what are the long-term complications of AML?
- DIC (e.g. acute promyelocytic leukaemia (APML))
- leukostasis
- TLS
