Acute leukaemia Flashcards by RK Splendid

auer rods are present in which leukaemia?

what other feature in the cell might you see?

AML

fine speckled granules

How well did you know this?

Not at all

Perfectly

what is a feauture of aeur rods?

peroxidase positive

How well did you know this?

Not at all

Perfectly

leukaemia of myeloBlasts and monoBlasts are?

AML

How well did you know this?

Not at all

Perfectly

leukaemia of lymphoBlasts are?

ALL

How well did you know this?

Not at all

Perfectly

list some symptoms of acute leukaemia and why they occur?

Bone marrow infiltration = pancytopaenia =

Anemia - fatigue
neutropaenia - Infections
thrombocytopaenia - mucosal bleeding

Multi-organ mets =

Hepatosplenomegaly
Headaches
Testicular enlargement
Bone pain eg tenderness over sternum !!
Generalised Lymphadenopathy - painless (as it is not an infection)

How well did you know this?

Not at all

Perfectly

How does ALL present?

Headaches
Testicular enlargement
Skin

How well did you know this?

Not at all

Perfectly

What diagnostic tests are conducted for acute leukamias?

Peripheral blood

Bone marrow biopsy + stain

How well did you know this?

Not at all

Perfectly

what would be the findings from ivx of ALL?

Peripheral blood:
Lymphoblasts - agranular, little cytoplasm, large nucleus to cytoplasm ratio
MCV - normo or macrocytic anaemia
Platelets low
WCC low or v high

Bone marrow:
Hypercellular balsts > 20%

How well did you know this?

Not at all

Perfectly

What would be the findings from ivx of AML?

Peripheral blood:
Myeloblasts - Aeur rods, granular
Monoblasts

MCV - normo or macrocytic anaemia
Platelets low
WCC low or v high

Bone marrow:
Hypercellular balsts > 20%

How well did you know this?

Not at all

Perfectly

what is the basic outline of treatment in acutee leukaemia’s?

youtube

Induction phase -
- eg to induce remission. give the following
A - High dose chemo
B - Myeloid growth factors (as chemo causes
pancytopaenia = inc infections due to neutropenia)
C - RBC, Platelets - if pancytopenia
Consolidation phase
- used in remission, to prolong remission

DNA microarrays - predict prognosis
CNS prophylaxis - intrathecal - in ALL

How well did you know this?

Not at all

Perfectly

what is the most common cancer in kids?

ALL

How well did you know this?

Not at all

Perfectly

Kids with down syndrome are predisposed to which cancer?

ALL

How well did you know this?

Not at all

Perfectly

epidemiology of ALL?

mostly young kids but bimodal so older patients too

How well did you know this?

Not at all

Perfectly

what aree the subtypes of ALL

WHO:

Pre-B : kids
Mature B
Pre-T: adults

lecture: B&T

How well did you know this?

Not at all

Perfectly

with immunophenotyping, what would you find with ALL?

B & Pre-B ALL:
B cell antigens - CD20, 19, CD10

T cell:
CD3+ (can be 3-8)

How well did you know this?

Not at all

Perfectly

Which translocations. might you find in B& Pre-B ALL?

prognosis? mnemonic?

Pre-B:
t9:22 -> philadelphia chromosome BCR ABL

t12:21 -> mirror, minor (kids), minor damage (good prognosis)

Mature B:
burkitts leukameia so t(8:14)

How well did you know this?

Not at all

Perfectly

which factors are indicative of poor prognosis in ALL?

Age > 60
WCC > 100,000
Mature B and pre-T
Philadelphia chromosome t9:22 (NOTE: in CML, this has good prognosis)
t4:11

An individual aged 40-60 comes in with sx of leukaemia, which is it. most likely to be?

Myeloid lineage so AML, APML or CML

lecture : median age for AML 65-70

An individual aged 60+ comes in with sx of leukaemia, which is it. most likely to be?

CLL

AML can bee associated with which genetic abnormalities?

Kleinfelters
Downs syndrome
Turner’s

List some important subclasses of AML

Based on myeloblast differentiation:

M2 - Myeloblastic with maturation - t(8:21) - most common

M3 - APML Acute promyeolocytic leukaemia - t(15:17) ->
associated with DIC.
good prognosis, unless they develop DIC

M5 - Monocytic AML

what do auer rods look like?

needle shaped crystals

what would immunohistochemistry show for

ALL
AML

ALL: Tdt+ PAS+

AML: Tdt- Myeloperoxidase+ (remember auer rods have these)

list possible mechanisms for developmeent of acute myeloid leukaemias. give examples

Chromosomal duplication
- > chrom 8,21
- > more proto-oncogenes
Chromosomal deletion
- > chrom 5/5q, 7/7q
- > less tumour suppressor genes
- > loss of DNA repair systems
Molecular abnormalities in patients with apparently normal chromosomes:
FLT3 - mutated in AML ‘Partial duplication’

list risk factors for leukaemia?

``` Familial or constitutional predisposition Irradiation Anticancer drugs - chemotherapy etc Cigarette smoking Unknown ```

what are type 1 and 2 abnormalities in forming of leukaemia ?

Type 1 abnormalities - promote proliferation & survival (anti-apoptosis) Type 2 abnormalities block differentiation and maturation (by blocking transcription factor function) this means we have blasts floating around

what is core binding factor leukaemia?

core binding factor is a transcription factor it is altered when some translocations occur eg t(8:21) inv16 or t16:16 causing leukaemia somehow

what genes are involved in t15:17 in APML?

PML gene chromosome 15: RARA gene chromosome 17: there is the classical and thee variant type of this condition Rara - retinoic acid receptor alpha PML - promyelocytic leukaemia gene

what are the local characteristics of monocytic AML/Acute monocytic leukaemia - M5?

Skin infiltration, gum infiltration -swelling & organomegaly remember mouth is 5 letters - M5

how does CNS disease infiltrate present in AML?

Cranial nerrve palsy retinal exudate & haemorrhage etc

how could bone marrow failure present in severe and life threatening situations?

septic shock renal failure DIC

how is AML treated? lecture

Chemo targetted molecular therapy transplant - if poor prognosis supportive care: RBC, Platelets, Antibiotics, Allopurinol, fluid + electrolyte balance FFP if DIC

in the treatment of APML, give examples of Molecularly targeted therapy?

1. All-trans-retinoic acid (ATRA) - vit A -> remember in APML its the PML-Rara fusion gene Rara: retinoic acid receptor alpha 2. A2O3

is lymphadenopathy more common in ALL/AML?

ALL

ALL in general has poor prognosis? true/false

false - depends on cytogenetic subtype

what are the Leukaemogenic mechanisms in ALL?

``` 1. Proto-oncogene dysregulation: chromosomal translocation causes: Fusion genes Wrong gene promoter Dysregulation by proximity to T-cell receptor (TCR) or immunoglobulin heavy chain loci ``` 2. Unknown – hyperdiploidy

the presence of hyperdiploidy in ALL has what prognosis ?

good one

Why does cytogenetic/molecular genetic category matter in ALL?

Ph-positive need imatinib

How is ALL treated?

same general principles as AML + CNS-directed therapy/prophylaxis -intrathecal Freeze sperm in bank the targeted molecular therapy is 1. imatinib - Tyrosine kinase inhibitor: Ph+ 2. Rituximab CD20+ ``` remission induction (prednisolone + vincristine) -> consolidation (Methotrexate + cyclophosphamide)+ CNS rx (intrathecal methotrexate + radiation) -> intensification -> maintenance (methotrexate + 6MP) ``` stem cell transplant lalst resort

compared to thee rest of AML, when does the block in cell maturation occur in APML?

later

what does t(15:17) lead to?

arrested differentiation of the promyelocytes abnormal retinoic acid metabolism (hence use of ATRA in rx)

what should the normal % of blasts be in: 1. the bone marrow 2. periphery

Bone marrow - 5% Periphery - 0%