Acute Leukaemia

Question 1

define acute leukaemia

Answer 1

neoplastic proliferation of lymphoid precursors (myeloid or lymphoid)

rapid onset

immature (blast cells high nuclear cytoplasmic ratio, diffuse chromatin pattern and nuclei )

bone marrow failure (infilitration and replcament of normal cells)

anaemia: fatigue breathlessness pallor
neutropenia: recurrant infection
thrombocytopenia: bleeding epistaxis bruising

Question 2

aml epidemiology

Answer 2

risk increases iwth age

worse prognosis

40% are adults

AML has abberation in chromsome/structure

Question 3

translocation t(15;17)

Answer 3

breakpoint in chromsome 15 and 17 translocation , distal parts of chromsome join to wrong ends

seen in acute promyelocytic leukaemia

also t(8;21)

Question 4

chromosonal duplication in AML

Answer 4

+8 and trisomy 21 AML and ALL predisposition, extra copies of proto-oncogenes

Question 5

chromsomal loss or deletion in AML

Answer 5

hotspots : 5/5q and 7/7q

possible loss of tumour supressor genes

one copy may reduce haemopoiesis or dna repair

can be partial or total

Question 6

genetic mutation in acute leukaemia

Answer 6

NPM1, CEBPA point mutation good prognosis

partial duplicaiton of FTL3 (BAD PROGNOSIS)

Question 7

risk factors for aml

Answer 7

familial /constitutional predisposition

irradiation

anticancer drugs (may damage precursor cells)

cigarette smoking

Question 8

Leukaemogensis type 1 and type 2 in AML

Answer 8

requires 2 hits to be pathogenic

type 1 promote proliferation and survival

type 2 block differentiation followed by apoptosis

Question 9

core binding factor

Answer 9

transcription factor master of haematopoiesis binds corepressors

seen in t(8:21) and inv(16)

Question 10

patient presents with haemorrhage cerebral or sudden onset of bruising/bleeding, which leukaemia?

Answer 10

acute promyelocytic leukaemia t(15;17), required early diagnosis

block is further down pathway abnormal promyelocytes

cogulation abnormality DIC and hyperactive fibrionolysis

hypergranular auer rods are present on blood film

variant form bilobed nuclei

Question 11

AML OR ALL

Answer 11

cytological features: blast cells auer roads cytoplasmic granules joined together to make crystal

cytochemistry myeloperoxidase stains brown

sudan black B identifies myeloid

non specific esterase myeloid

Immunophenotyping: antigens on cell surface

flow cytometry, immunophenotyping. express Tdt (ALL) immature cell

AML : MPO

Question 12

clinical features of AML

Answer 12

Bone marrow failure (anaemia neutropenia thromboycytopenia)

splenomegaly hepatomegaly

gum infiltration (if monocytic ) overgrowth of gums

lymphadenopathy

skin (superficial infection)

CNS (monocytic) cranial nerve palsy

may present with septic shock

pin point petechiae

DIC - can present with peripheral vascular obstruction

Hypervisocity if wbc very high retinal haemorrhage/exudates

Question 13

diagnosis of AML

Answer 13

blood film

auer rods or granules

aleukaemic leukaemia -> do a bone marrow aspirate

immunophenotyping

cytogenetic studies all patients prognostic factor and to select treatment (apml direct treatment affect)

Question 14

which aml has good prognosis

Answer 14

t(8:21) and inv(16) core binding

t15:17 apml

Question 15

treatment of aml

Answer 15

supportive care, red cell platlet ffp if DIC

antibiotics , long line central port

allopurinol from dying cells uraemic acid

chemotherapy combination therapy at least 2 drugs, synergistic , non overlapping toxicity

Question 16

treatment of apml

Answer 16

A drug called all-trans retinoic acid (ATRA)

promyeloycytes mature so are no longer leukaemia cells

arsenic trioxide has a similar effect

has good prognosis

Question 17

ALL clinical features (how is it different to AML)

Answer 17

similar to AML bone marrow failure etc. however lymphadenopathy more common (thymic enlargment)

also bone pain in long bones more common

Question 18

ALL genetic prognosis mutations

Answer 18

hyperdiploidy t12:21 t1:19 good

hypodiploidy t4;11 - poor

t9;22 philadelphia chromsome - improved with tyrosine kinase inhibitors ( bcr-abl1 fusion gene)

(feature of chronic myeloid leukaemia but also a feature of all in older/adults )

Question 19

what is the importance of immunophenotyping in ALL?

Answer 19

aml vs all treated differently

t-lineage (15%) b lineage 85% ALL treated differently

other invesitgations : blood count/film bone marrow aspirate immunophenotyping (cytogenic always), blood grouping lft electrolytes

philidelphia +ve need imatinib

Question 20

what additional therapy is needed for ALL vs AML?

Answer 20

systemic + CNS directed as it migrates into CSF

give drugs into CSF or those which cross BBB

treat longer for boys (+1yr) as testes is often affected