Ha - Acute Leukaemia Flashcards
3 year old girl has splenomegaly, lymphadenopathy, low platelets, high WCC. Most likely diagnosis?
ALL
define acute leukaemia
neoplastic condition characterised by rapid onset, high mortality if untreated, blast cells and bone marrow failure
3 types of bone marrow failure and the sx they manifest
anaemia - pallor, SoB, fatigue
neutropenia - infections
thrombocytopaenia - bleeding
name monocyte cells
neutrophils
eosinophils
which cell gives rise to AML
multipotent myeloid stem cell or pluripotent stem cell
which cell gives rise to ALL
common lymphoid stem cell
what cell type is dominant in acute leukaemias
BLAST CELLS
granules on a cell indicate what
myeloid cell
age trend in AML
increased with age, except blip in first year of life
median age of AML
65-70
how does age affect prognosis of AML q
prognosis worse with icnreasing age
what % of adults cured of AML
40%
what causes AML
abberations in chromosome count / structure –> eg translocations, trisomy
which type of acute leukaemia gets abnormal regulation of genes
ALL
which leukaemia has creation of new genes involved
ALL and AML
is chromosomal duplication common in AML
yes
which chromosomes are most likely to be duplicated to cause AML
8 and 21
is chromosome loss / deletion common in AML
yes
which chromosomes are deleted / lost in AML
5 and 7
how does chromosome deletion / duplication cause AML
deletion - loss of TSG
duplication - more oncogenes
what type of molecular abnormalities can be seen in normal chromosomes in acute leukaemia
point mutations
loss of TSG
partial duplication
cryptic deletion
describe the cell development process that leads to AML formation
block in maturation of myelocyte cells so blast cells accumulate
why do people get AML
familial / syndromic predisposition
irridation
anti cancer drugs
smoker
unknown !
how many molecular insults are needed to cause leukaemia
at least 2
what are type 1 abnormalities in AML
promote proliferation and survival
what are type 2 abnormalities in AML
block differentiation (which normally preceeds apoptosis)
for which specific type of AML is the mechanism understood and a cure available to patients
t(15;17)
complication of t(15;17) AML
DIC
what genes are fused in t(15;17) AML
PML and RARA
is transcription factor disturbance enough to cause AML
no - need further genetic hit
what cells have auer rods
myeloid cells
what confirms AML vs ALL
immunophenotyping
which stains are positive in AML but negative in ALL
myeloperoxidase
sudan black
non specific esterase
how does immunophenotyping work
AB recognises specific antigen. AB is then flagged with a immunoflurescent dye to recognise it
Sx of AML
anaemia, neutropenia, thrombocytopaenia
hepatosplenomegaly
lymphadenopathy / gum infiltration
which type of AML has gum infiltration
acute monocytic leukaemia
which type of AML gets CNS disease (eye palsy etc) more commonly than others
acute monocytic
also ALL
what can bleeding in AML lead to
DIC
what eye signs can be seen due to AML and why
papilloedema / retinal haemorrhages due to hyper-viscosity of blood
how is AML diagnosed
blood film - diagnostic usually
what is seen on blood film to diagnose AML
blasts / auer rods
leukaemia Sx. No abnormal cells on film. What do you do?
bone marrow aspirate
leukaemia Sx. No abnormal cells on film. likely dx?
aleukaemic leukaemia - blasts confined to bone marrow so cant see on film
why are cytogenetoc / molecular studies done on AML pts?
prognostic value
selective tx targets
which gene patterns convey the best prognosis of AML
t(15;17)
t(8;21)
inv(16) or t(16;16)
which gene patterns convey the worst prognosis of AML
-5, del 5
-7, 3q-
complex
supportive care Tx of AML
red cells
platelets
FFP
Abx
long line
allopurinol
mx of AML
supportive care
chemo
targeted molecular therapy
transplant
describe chemo regime of AML
cell cycle specific drugs
4-5 courses over 6 months
- remission induction x2
- consolidation x2 or 3
give some examples of molecular therapies for acute promyelocytic leukaemia
all trans retinoic acid (ATRA)
arsenic trioxide
molecular therapies for acute Ph+ leukaemia
tyrosine kinase inhibitors
antibody tx for AML
gemtuzumab
ozogamicin
what determines prognosis of AML
pt charactristics
morphology / immunophenotyping
response to tx
