Concepts in malignant haematology Flashcards
what are the key actions of normal haemopoiesis
self-renewal (stem cells) proliferation differentiation maturation apoptosis
what are the non-lymphoid cells
erythrocytes
platelets
granulocytes
macrophages
how do you identify normal non-lymphoid cells
Morphology
cell surface antigens (glycophorin A = red cells)
enzyme expression (myeloperoxidase = neutrophils)
how do you identify normal progenitors/ stem cells
cell surface antigens (immunophenotyping)
cell culture assays
what happens in malignant haemopoiesis
increased numbers of abnormal and dysfunctional cells
loss of normal activity
due to:
- increased proliferation
- lack of differentiation
- lack of maturation
- lack of apoptosis
what is acute leukaemia
proliferation of abnormal progenitors with a block in differentiation/maturation
acute because cells proliferate quickly
what is the difference between acute myeloid leukemia and acute lymphoblastic leukaemia
in acute myeloid leukemia the myeloid progenitor cells rapidly proliferate
in acute lymphoblastic leukemia the lymphoid progenitors rapidly proliferate
what is chronic myeloid leukemia
proliferation in abnormal myeloid progenitor cells
no block to differentiation/maturation (so normal mature cells are also produced)
therefore happens slower
causes of haematological malignancy
Genetic
Epigenetic
environmental interaction
‘two hit hypothesis’
mutations in regulatory genes (driver mutations and passenger mutations)
what do ‘driver’ mutations in haemopoesis do
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
what are the differences in normal and malignant haemopoeisis clones
normal haemopoeisis - ‘polyclonal’
malignant haemopoeisis - ‘monoclonal’
what are the two types of haematological malignancy based on anatomical site involved
leukaemia - blood
lymphoma - lymph noid involvement with lymphoid malignancy
myeloma - plasma cell malignancy in marrow
what are histological features of aggressive leukemia/lymphoma
large cells with high nuclear-cytoplasmic ratio
prominent nucleoli
rapid proliferation
what is acute leukaemia
progressive clonal malignancy with maturation defects
‘blasts’ > 20% in either peripheral blood or bone marrow
loss of normal haemopoietic reserve
what are the two types of acute leukaemia
Acute myeloid Leukaemia (AML)
Acute lymphoblastic Leukaemia (ALL)
what is acute lymphoblastic leukaemia (ALL)
malignant disease of primitive lymphoid cells (lymphoblasts)
most common childhood cancer
how does acute lymphoblastic leukaemia present
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
what is acute myeloid leukaemia
malignant disease of primitive myeloid cells (myeloblasts)
who gets acute myeloid leukaemia and how does it present
elderly (>60)
similar presentation to acute lymphoblastic leukaemia (marrow failure)
subgroups have characteristic presentation
what investigations are done for acute leukaemia
Blood count and film
Coagulation screen
what does the blood film look like in acute leukaemia (important)
Reduction in normal cells
Presence of abnormal cells (blasts with high nuclear:cytoplasmic ratio)
what is seen on blood film in acute myeloid leukaemia
Auer Rod
> 20% blasts
what investigation is required to definitely distinguish between acute myeloid leukaemia and acute lymphoblastic leukaemia
Immunophenotyping
shows the lineage associated proteins on the cells
what are the curative treatments for acute lymphoblastic leukaemia
Multi-agent chemotherapy
can last up to 2-3 heats
different phases of treatment of varying intensity
targeted treatments in certain subsets
what are the curative treatments of acute myeloid leukaemia
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
what problems occur with bone marrow suppression
Anaemia
Neutropenia
-infections
gram-ve bacteria can cause life-threatening sepsis in neutropenic patients
Thrombocytopenia
-bleeding, purport, petechiae
complications of chemotherapy for leukaemia
Nausea & vomiting hair loss liver, renal dysfunction tumour lysis syndrome infections (bacterial are common, sometimes fungal occurs) infertility cardiomyopathy
others
what is ‘remission’ of acute leukaemia
<5% marrow blasts with recovery of normal haemopoiesis
many patients see relapse
some patients die from treatment related toxicity
cure rates for acute leukaemia
childhood ALL 85-90%
adult ALL 30-40%
Adult AML <60 40-50%
Adult AML >60 10% or less
what leukaemia subtype is associated with disseminated intravascular coagulation
Acute promyelocytic leukaemia
sub type of acute myeloid leukaemia
