Concepts in malignant haematology

Question 1

what are the key actions of normal haemopoiesis

Answer 1

self-renewal (stem cells) 
proliferation 
differentiation 
maturation 
apoptosis

Question 2

what are the non-lymphoid cells

Answer 2

erythrocytes
platelets
granulocytes
macrophages

Question 3

how do you identify normal non-lymphoid cells

Answer 3

Morphology

cell surface antigens (glycophorin A = red cells)

enzyme expression (myeloperoxidase = neutrophils)

Question 4

how do you identify normal progenitors/ stem cells

Answer 4

cell surface antigens (immunophenotyping)

cell culture assays

Question 5

what happens in malignant haemopoiesis

Answer 5

increased numbers of abnormal and dysfunctional cells

loss of normal activity

due to:

• increased proliferation
• lack of differentiation
• lack of maturation
• lack of apoptosis

Question 6

what is acute leukaemia

Answer 6

proliferation of abnormal progenitors with a block in differentiation/maturation

acute because cells proliferate quickly

Question 7

what is the difference between acute myeloid leukemia and acute lymphoblastic leukaemia

Answer 7

in acute myeloid leukemia the myeloid progenitor cells rapidly proliferate

in acute lymphoblastic leukemia the lymphoid progenitors rapidly proliferate

Question 8

what is chronic myeloid leukemia

Answer 8

proliferation in abnormal myeloid progenitor cells

no block to differentiation/maturation (so normal mature cells are also produced)

therefore happens slower

Question 9

causes of haematological malignancy

Answer 9

Genetic
Epigenetic
environmental interaction

‘two hit hypothesis’

mutations in regulatory genes (driver mutations and passenger mutations)

Question 10

what do ‘driver’ mutations in haemopoesis do

Answer 10

select ‘clones’

(a population of cells derived from one single parent cell which has a mutation shared by all the cells )

and causes them to divide more

Question 11

what are the differences in normal and malignant haemopoeisis clones

Answer 11

normal haemopoeisis - ‘polyclonal’

malignant haemopoeisis - ‘monoclonal’

Question 12

what are the two types of haematological malignancy based on anatomical site involved

Answer 12

leukaemia - blood

lymphoma - lymph noid involvement with lymphoid malignancy

myeloma - plasma cell malignancy in marrow

Question 13

what are histological features of aggressive leukemia/lymphoma

Answer 13

large cells with high nuclear-cytoplasmic ratio
prominent nucleoli
rapid proliferation

Question 14

what is acute leukaemia

Answer 14

progressive clonal malignancy with maturation defects

‘blasts’ > 20% in either peripheral blood or bone marrow

loss of normal haemopoietic reserve

Question 15

what are the two types of acute leukaemia

Answer 15

Acute myeloid Leukaemia (AML)

Acute lymphoblastic Leukaemia (ALL)

Question 16

what is acute lymphoblastic leukaemia (ALL)

Answer 16

malignant disease of primitive lymphoid cells (lymphoblasts)

most common childhood cancer

Question 17

how does acute lymphoblastic leukaemia present

Answer 17

symptoms of marrow failure (anaemia, infections, bleeding)

Leukaemia effects - high count with obstruction of circulation, involvement of areas outside the marrow and blood (extra medullary)

bone pain

Question 18

what is acute myeloid leukaemia

Answer 18

malignant disease of primitive myeloid cells (myeloblasts)

Question 19

who gets acute myeloid leukaemia and how does it present

Answer 19

elderly (>60)

similar presentation to acute lymphoblastic leukaemia (marrow failure)

subgroups have characteristic presentation

Question 20

what investigations are done for acute leukaemia

Answer 20

Blood count and film

Coagulation screen

Question 21

what does the blood film look like in acute leukaemia (important)

Answer 21

Reduction in normal cells

Presence of abnormal cells (blasts with high nuclear:cytoplasmic ratio)

Question 22

what is seen on blood film in acute myeloid leukaemia

Answer 22

Auer Rod

> 20% blasts

Question 23

what investigation is required to definitely distinguish between acute myeloid leukaemia and acute lymphoblastic leukaemia

Answer 23

Immunophenotyping

shows the lineage associated proteins on the cells

Question 24

what are the curative treatments for acute lymphoblastic leukaemia

Answer 24

Multi-agent chemotherapy

can last up to 2-3 heats
different phases of treatment of varying intensity

targeted treatments in certain subsets

Question 25

what are the curative treatments of acute myeloid leukaemia

Answer 25

normally intensive multi-agent chemotherapy

2-4 cycles of chemo over 5-10 days (with 2-4 weeks recovery)

prolonged hospitalisation

targeted treatments in subsets

Question 26

what problems occur with bone marrow suppression

Answer 26

Anaemia

Neutropenia
-infections
gram-ve bacteria can cause life-threatening sepsis in neutropenic patients

Thrombocytopenia
-bleeding, purport, petechiae

Question 27

complications of chemotherapy for leukaemia

Answer 27

Nausea & vomiting 
hair loss 
liver, renal dysfunction 
tumour lysis syndrome 
infections (bacterial are common, sometimes fungal occurs) 
infertility 
cardiomyopathy 

others

Question 28

what is ‘remission’ of acute leukaemia

Answer 28

<5% marrow blasts with recovery of normal haemopoiesis

many patients see relapse

some patients die from treatment related toxicity

Question 29

cure rates for acute leukaemia

Answer 29

childhood ALL 85-90%
adult ALL 30-40%
Adult AML <60 40-50%
Adult AML >60 10% or less

Question 30

what leukaemia subtype is associated with disseminated intravascular coagulation

Answer 30

Acute promyelocytic leukaemia

sub type of acute myeloid leukaemia