acute leukaemia Flashcards
define acute leukaemia
accumulation of early myeloid or lymphoid precursors in the bone marrow, blood and other tissues.
3 most likely causes of acute leukaemia
somatic mutation in early progenitor cells.
terminal event in a pre–existing blood disorder e.g. myeloproliferative disease.
chemotherapy.
what are the 2 main subgroups of acute leukaemia
acute myeloid leukaemia
acute lymphoblastic leukaemia.
Histological appearance of AML
blast cells in the peripheral blood
high white cell count, large immature cells with nuclei still present
high nucleus to cytoplasmic ratio and contains granules.
Histological appearance of ALL
blast cells in the peripheral blood- smaller and rounder than in AML
smaller cytoplasm than AML
what are the most common clinical presentations of acute myeloid leukaemia
- bone marrow failure
- anaemia
- infections (staphylococcus aureus, perianal, oral candida)
- bruising and haemorrhage.
- DIC
- lymph gland swelling (groin, axilla, cervical)
- hepatomegaly.
- gum hypertrophy
what are the most common clinical features of acute lymphoblastic leukaemia
Oral candida.
diagnosis of leukaemia.
morphology cytochemistry flow cytometry- immunological markers cytogenetics- FISH for genetic leukaemia's molecular techniques- PCR for mutations
What are the 2 types of classifications of AML
FAB-morphologically based on what is seen.
WHO- classification is risk adapted.
what immunological markers are used to determine leukaemia
monoclonal antibodies determination
Immunofluorescence (in particular FACS- fluorescence activated cell sorting).
how does flourochrome-coupled antibody labelling work.
- Cell surface covered with antigens
- Antibody with flurochrome attaches,
- Cells streamed into a single line, pass laser beam which shines beam,
- They absorb light and then give of a specific wavelength to the colour they are.
which genetic abnormality has a good prognosis in AML
t(8;21) and t(15:17)
which genetic abnormality has bad prognosis in AML
monosomy 7
what are the different types of chromosomal abnormalities in ALL
high hyperdiploidy
hyperdiploidy
pseudodiploidy
hypodiploidy
what define high hyperdiploidy
> 50 chromosomes.
what are the 2 types of chromosomal abnormalities in ALL
structural and numerical.
what factors result in poor prognosis for ALL
age WBC count Males- ALL develops in the testes. cytogenetic abnormalities poor response to treatment T-ALL and null ALL
how are molecular abnormalities monitor in acute leukaemia
e.g. where are the results obtained from
bone marrow and peripheral blood.
What is the molecular pathology of AML (what causes AML)
abnormal cell proliferation
block in differentiation
Tumour suppression
Management of AML
• Induction treatment to obtain remission, then consolidation with further courses of combination chemotherapy
younger patient- bone marrow transplant.
management of ALL
All patients receive induction chemotherapy, intensive consolidation chemotherapy and prophylaxis of meningeal leukaemia with intrathecal methotrexate and cranial irradiation
Chemotherapy and bone marrow transplant
how is bone marrow obtained
Siblings-25% chance of full HLA match.
Cord blood transplant= collected at birth.
Donor list.
what is Peripheral Blood Stem Cell Transplantation
Bone marrow cells are forced into peripheral blood
what condition is will a patients undergoing chemotherapy develop
neutropenia
define neutropenic fever
pyrexia in the presence of a neutrophil count of less than 1.0 x 109/l
what are patients who develop neutropenia at risk of
neutropenic sepsis- developing overwhelming gram negative or gram positive infection
how is neutropenic sepsis managed in order to reduce the risk of infection
immediate administration of broad spectrum IV antibiotics (often Tazocin and Gentamicin
how can neutropenic sepsis be prevented
protective isolation
prophylactic antibiotics
use of granulocyte colony stimulating
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