Malignant haem

Question 1

how are normal mature cells identified

Answer 1

morphology

cell surface antigens (e.g. glycophorin A = red cells)

enzyme expression (e.g. myeloperoxidase = neutrophils)

Question 2

how are proginators/stem cells identified

Answer 2

cell surface antigens - immunophenotyping e.g. CD34

cell culture assays

Question 3

what happens in malignant haemopoiessi

Answer 3

increased numbers of dysfunctional cells and may have loss of the normal haemopoietic reserve

one or more of:
increased prolif
lack of differentiartion
lack of maturation
lack of apoptosis

Question 4

what happens to the cells in acute leukemia

Answer 4

abnormal proliferation - large number of similar looking cells
lack of maturation

Question 5

causes of haematological malignancies

Answer 5

genetic

enviro

somatic mutations in regulatory genes: driver V passenger mutations [noise]

multiple mutations or can be one single catastrophic event

recurrent cryogenic abnormalities -> contributory rather than the cause of the cancer

Question 6

difference between passenger and driver mutations

Answer 6

driver - confer growth advantage, positively selected during the evolution of the cancer

passenger - do not confer growth advantage, happened to be present in an ancestor of the cancer cell when it acquired on of its driver

Question 7

what is the concordant rate with twins in ALL

Answer 7

10-15%

Question 8

how many people over the age of 65 for driver mutations that are associated with haematological malignancies

Answer 8

around 10%

Question 9

how can the genetic defect be found in ALL

Answer 9

by investigating the guthrie card

Question 10

normal haemopoiesis

malignant haemopoeisis

Answer 10

polyclonal

monoclonal

Question 11

classification of haematological malig

Answer 11

acute/chronic presentation - depends on type and stage of defect

anatomical site: -medullary/extramedullary
-leukaemia (blood)/lymphoma

lineage:

• myeloid
• lymphoid

Question 12

types of lymphomas

Answer 12

high grade - aggressive histology: large primitive cells and clinically aggressive

low grade - generally less aggressive

Question 13

what is odd about chronic lymphocytic leukaemia

Answer 13

involves not just blood/bone marrow but lymph nodes

Question 14

myeloma is what

Answer 14

plasma cell malignancy of the bone marrow

Question 15

what are acute leukaemia

Answer 15

rapidly progressive clonal malignancy of the marrow/blood with maturation defects

excess of blasts >20% in either peripheral blood or bone marrow

decrease/loss of normal haemopoietic reserve

Question 16

types of acute leukaemia

Answer 16

actual myeloid leu

acute lymphoblastic leu

Question 17

what is ALL

Answer 17

malignant disease of lymphocytes

Question 18

who is ALL common in

Answer 18

most common childhood cancer

Question 19

presentation of ALL

Answer 19

marrow failure - anaemia, infection, bleeding
leukaemia effects - high ECC, nervous system effects, lymph nodes sometimes causing venous obstruction [SVC obstruction]
bone pain - v severe

Question 20

acute myeloid leu more common in who

presentation

Answer 20

elderly >60
de novo or secondary
presentation similar to aLL -> doesn’t involve CNS

Question 21

what other ways can some subgroups of AML present

Answer 21

DIC

Gum infiltration

Question 22

investigations for acute leu

Answer 22

blood count and film - low hb, white cells may be high, low platelets, low neutrophils
film - Auer rods in acute myeloid leukaemia

coag screen

bone marrow aspirate

Question 23

bone marrow aspirate

Answer 23

morphology - mononuclear, high nuclear: cytoplasmic ration, very metabolically active

immunophenotype if no auer rods can be seen - CD33 is seen on myeloid cells not lymphoid cells, CD34

cytogenetics - help w dx and prognostic significance

trephine (piece of bone) - better assessment of cells if aspirate sub optimal

Question 24

why is immunophenotyping required or a definitive dx

Answer 24

cells from AML and ALL look alike

treatment for both are different

Question 25

treatment for acute leukaemia

Answer 25

multi agent chemo

Question 26

treatment for ALL

Answer 26

lasts for 2-3 years

Question 27

treatment for AML

Answer 27

normally intensive

prolonged hospitalisation

Question 28

hickman line

Answer 28

chemo generally given through a hickman line

goes through the subclavian vein

Question 29

problems of marrow suppression due to treatment

Answer 29

anaemia

neutropenia = infections - gran neg can cause fulminant life threatening sepsis in neutropenic px

thrombocytopenia - bleeding: purpura, petechiae

Question 30

complications of treatment

Answer 30

n+v
hair loss
liver/renal dysfunction 
tumour lysis dysfunction - during first course of treatment 
infection 

late effects - loss of fertility, cardiomyopathy with anthracycline

Question 31

management of infections due to treatment

Answer 31

bacterial: empirical treatment w broad spec ab as soon as neutropenic fever

fungal - if prolonged neutropenia and persisting fever unresponsive to anti bacterial agents

protozoal

Question 32

outcome of treatment

Answer 32

most go into remission
but depending on the can relapse
some will die to treatment related toxicity

Question 33

childhood outcomes of treatment

Answer 33

childhood ALL >85% cure rates
Adult ALL 30-40%
Adult ALL <60 50%
Adult AML >60 <10%

Question 34

what can be given that may be curative after initial therapy or at relapse

Answer 34

allogeneic stem cell transplantation

Question 35

what type of acute leu is assoc with DIC

how is this treated

Answer 35

acute peomyelocytic leuk

vitamin and arsenic to treat