Acute Leukaemia Flashcards
Who do ALL and AML usually occur in?
ALL: young
AML: elderly
What triad does bone marrow failure present as?
Anaemia
Thrombocytopoenia
Neutropoenia
Summarise aetiology of acute leukaemia
Acute uncontrolled proliferation of immature blast cells
This interfered with development and function of healthy WBC/RBC/platelets
- loss of ability to differentiate > stuck in blast stage, don’t function
- uncontrollable division > crowding out of healthy cells
What kinds of abnormalities trigger AML?
Chromosome abnormality (recurrent) Or Molecular changes (with apparently normal chromosomes)
What types of chromosome abnormalities occur in AML?
Duplication (usually trisomy, e.g. 21) Loss Translocation (e.g. APML - t(15,17)) Inversion Deletion
What are RF to get AML?
Familial
Irradiation
Anticancer drugs
Cigarette smoking
What does leukaemia development require for AML?
At least 2 hits
What are type 1 and type 2 abnormalities in AML?
- Type 1 abnormality: promote proliferation and survival (anti-apoptosis)
- Type 2 abnormality: blocks differentiation, leading to accumulation of blast cells
What mutations can occur. on the core binding factor?
TRANSLOCATION: t(8,21)
fuses RUNX1 with RUNZ1T1
Causes AML
INVERSION of Chr 16
fuses CBF beta to MYH11
What is the translocation of APML?
t(15,17)
What occurs in APML?
Excess of abnormal promyelocytes
What abnormal genes can t(15,17) form?
Type 1: FLT2-ITD
Type 2: PML-RARA
What structures are abnormal within promyelocytes in APML?
AUER RODS
How can you differentiate AML from ALL
Cytological:
- AML: Auer rods, fine speckled granules
Cytochemistry: (all +ve for AML, -ve for ALL)
- myeloperoxidase
- Sudan black
- non-specific esterase
Immunophenotyping
- flow cytometry
- immunohistochemistry
- immunocytochemistry
What clinical presentations occur following local infiltration?
splenomeg
hepatomeg
gum infiltration
lymphadenopathy
How can you diagnose AML?
Blood film (Auer rods, granules) Immunophenotyping Bone Marrow aspirate Cytogenetic studies Molecular studying
What is treatment of AML
Supportive care (RBC, platelets, FFP/cryoprecipitate, antibiotics, long line, allopurinol)
Chemotherapy
Transplanted molecular therapy
transplantation
Why is combination chemo always used in AML?
Different MOAs
Synergy
Non-overlapping toxicity
What are important clinical features of ALL?
- Bone marrow failure triad
- Local infiltration (lymphadenopathy, thymic enlargement, splenomegaly, hepatomegaly, testes/CNS/kidney invasion, bone pain)
What are the 2 possible sources of ALL?
T cells
B cells
What type of ALL can you treat with TK inhibitors?
Philadelphia chromosome
t(9,22)
Name one TKinhibitor?
Imatinib
What are specific therapies for ALL?
Systemic chemo
CNS directed therapy
molecular targeted tx
transplantation
How long do you give systemic chemo for in ALL?
2-3 years
How does chemo change for boys compared girls in ALL?
Give boys chemo for longer
Because the testes are a site of accumulation for lymphoblasts
Why do you give CNS directed therapy in ALL?
To prevent development of long term CNS disease
What is prognosis for ALL like depending on age group?
VERY GOOD if CHILDREN
BAD if ADULT
