ACUTE LEUKAEMIAS Flashcards
What are the two types of acute leukaemia?
Acute myeloid leukaemia (AML)
Acute lymphoid leukaemia (ALL)
What is the underlying mechanism of acute leukaemia?
Failure of normal differentiation of haemopoietic stem cells and progenitors into mature cells leading to accumulation of primitive leukaemic cells within the bone marrow. This ultimately leads to bone marrow failure.
What cells are made from the myeloid progenitors in the bone marrow?
Neutrophils Eosinophils Monocytes Basophils Megakaryocytes Erythrocytes
What cells are made from the lymphoid progenitors in the bone marrow?
Lymphocytes
What do we call the cells that accumulate in the bone marrow in acute myeloid leukaemia?
Myeloblasts
What do we call the cells that accumulate in the bone marrow in acute lymphoid leukaemia?
Lymphoblasts
How do people with acute leukaemia present?
Symptoms of anaemia (shortness of breath, lethargy, pallor)
Symptoms of thrombocytopenia (bleeding and bruising)
Symptoms of neutropenia (susceptible to infection, neutropenic sepsis)
Bone pain
Headache
Leukostasis syndrome - causing symptoms of stroke or respiratory disease
What are the inherited risk factors for acute leukaemia?
Down’s syndrome
Fanconi’s anaemia - DNA repair mutation
Bloom’s syndrome - DNA helicase mutation
Klinefelter’s synrome - XXY males
Wiskott-Aldrich syndrome - eczema-thrombocytopenia-immunodeficiency syndrome
Ataxia telangiectasia - neurodegenerative leading to poor coordination and dilated blood vessels. Repair of DNA also affected
Osteogenesis imperfecta - brittle bone disease (blue sclera)
Neurofibromatosis type 1 - benign neurofibromas
What will the WCC count of someone with acute leukaemia show?
Can be very low - due to bone marrow failure
Can be high - due to spill over from bone marrow of myeloblasts or lymphoblasts
What type of bleeding and bruising is associated with acute leukaemia?
Associated with thrombocytopenia so platelets not clotting factors
Bruising of the mucous membrane - so inside mouth
Bleeding also from mucous membrane - so melena
But also generalised bleeding - from venopuncture, menorrhagia
What age group does acute myeloid leukaemia most often affect?
Middle aged to elderly
What age group does acute lymphoid leukaemia most often affect?
Children - most common cancer in children
What are the common sites of infiltration of acute lymphoid leukaemia?
Meninges Liver Spleen Mediastinum Testes
What are the common sites of infiltration of acute myeloid leukaemia?
Skin
Gum
What are the mandatory investigations for someone with suspected acute leukaemia?
FBC Coagulation U+Es LFTs Bone marrow aspirate or trephine biopsy
Once the diagnosis of acute leukaemia has been made, what further investigations are needed to aid with further distinction of the disease and hence treatment options?
Immunophenotyping - discern between AML and ALL
Cytogenetic and molecular studies
Lumbar puncture in patients with ALL - looking for meningeal infiltration
Chest x-ray - particularly in T cell ALL
What are the chromosomal abnormalities associated with acute myeloid leukaemia that hold a relatively good prognosis with chemotherapy?
t(8;21)
Inv(16)
t(15;17)
What are the chromosomal abnormalities associated with acute myeloid leukaemia that hold a relatively poor prognosis even with chemotherapy?
t(9;22)
What drug should be given in anticipation of chemotherapy treatment for acute leukaemia?
Allopurinol
What is the initial aim of treatment for acute leukaemia?
Complete remission (>5% of leukaemic blast within bone marrow)
What are some of the possible immediate side effects of chemotherapy used in the treatment of acute leukaemias?
Alopecia Nausea and vomiting Mucositis Hepatic dysfunction Further haematological toxicity Peripheral and CNS neuropathy
What are some of the later side effects of chemotherapy used in the treatment of acute leukaemias?
Infertility Cardiomyopathy Pulmonary fibrosis Secondary malignancies Growth failure Cognitive dysfunction
What are the chemotherapeutic agents used in the treatment of acute myeloid leukaemia?
Anthracyclines - daunorubicin and idarubicin
Cytosine arabinoside
Etoposide
How many cycles of chemotherapy does it usually take to achieve complete remission in adults patient with acute myeloid leukaemia?
Achieved in 70-80% of cases after one or two cycles
Once complete remission has been achieved in an adult with acute myeloid leukaemia, how many more cycles of chemotherapy will they undergo?
Another two
Which group of leukaemia patients would be given all-trans-retinoic acid, in combination with anthracylcines?
Acute promyelocytic leukaemia (APL), a sub group of AML
Other than chemotherapy, what other treatment options are there for patients diagnosed with acute myeloid leukaemia?
Stem cell transplantation from a HLA identical sibling
What are the three main differences between the treatment strategy for acute lymphoid leukaemia versus acute myeloid leukaemia?
- ALL treatment directed at treating or preventing seeding in the CNS
- Additional drugs in ALL including vincristine and L-asparaginase, and imatinib which is highly active in Philadelphia-positive ALL
- Maintenance treatment in ALL is up to two years with oral drugs such as methotrexate.
What are the three forms of treatment used in acute lymphoid leukaemia in order to prevent seeding of blasts in the CNS?
- Intrathecal administration of chemotherapy agents
- Systemic administration of high dose methotrexate
- Cranial radiotherapy
