Concepts in malignant haematology and acute leukaemia Flashcards
What are the kinetics of normal haemopoeisis
Self renewal Proliferation Differentiation/lineage commitment Maturation Apoptosis
How can you identify normal mature non-lymphoid cells
Morphology eg blood film
cell surface antigens
enzyme expression
how can you identify normal progenitors/stem cells
cell surface antigens through immunophenotyping
cell culture assays
define malignant haemopoeisis
increased numbers of abnormal or dysfunctional cells
ie loss of normal haemopoeisis
what are the abnormalities in haemopoeitic kinetics that lead to malignancy
increased proliferation
decreased: differentiation, maturation, apoptosis
what is the pathophysiology behind acute leukaemia
proliferation of abnormal progenitors with a block in differentiation/maturation
eg common myeloid progenitors proliferate but do not differentiate
in chronic leukaemia, there is proliferation of abnormal progenitors with/without blocking of differentiation
without
what are ‘clones’
population of cells derived from a single parent cell
Driver mutations can select ‘clones’
true or false
true
why can genetic markers be detected in clones
because the parent cell has a genetic marker (chromosomal abnormality, driver mutation …) that is shared by the daughter cells
clones can diversify but still contain a similar genetic backbone
Normal haemopoeisis is polycloncal/monoclonal
Malignant haemopoeisis is polycloncal/monoclonal
normal = polyclonal malignant = monoclonal
what is the difference between driver and passenger mutations
driver mutations confer a growth advantage on cells selected during cancer evolution
passenger cells dont, they just happen to be there
how can you classify haematological malignancies
based on:
lineage
developmental stage
anatomical site
How can haematological malignancies be classified according to lineage
myeloid
lymphoid
How can haematological malignancies be classified according to developmental stage
example:
Pro B stage –> acute lymphoblastic leukaemia
B cell stage –> chronic lymphoblastic leukaemia
Plasma cell stage –> myeloma
How can haematological malignancies be classified according to anatomical site
blood involvement = leukaemia
lymph node involvement with lymphoid malignancy = lymphoma
CLL only involves blood, true or false
false
CLL can involve blood and lymph nodes
which are more aggressive?
Acute leukaemias + high grade lymphomas OR
chronic leukaemias + low grade lymphomas
Acute leukaemias + high grade lymphomas
what are histological features of aggression
large cells
high N:C ratio
prominent nucleoli
rapid proliferation
which presents with bone marrow failure, acute or chronic leukaemia
acute
define myeloma
neoplastic disease of plasma cells in the bone marrow
define lymphoma
neoplastic disorder of mature lymphocytes in lymphoid tissues
define acute leukaemia
neoplastic disorder of immature ‘blasts’ in bone marrow
what are the subtypes of acute leukaemia
acute lymphoblastic leukaemia (ALL) - lymphoid lineage
acute myeloid leukaemia (AML) - myeloid lineage
define chronic leukaemia
neoplastic disorder of mature white blood cells in bone marrow
what are the subtypes of chronic leukaemia
chronic lymphoblastic leukaemia (CLL) - lymphoid lineage
chronic myeloid leukaemia (CML) - myeloid lineage
what are myeloproliferative disorders
group of neoplastic disorders involving bone marrow cells that produce RBC, platelets and fibroblasts
what are the subtypes of myeloproliferative disorders
Polycythaemia Rubra Vera - ^ RBC
Essential Thrombocythaemia - ^ platelets
Myelofibrosis
define myelodysplasia
pre cancerous disease of bone marrow where dysplastic cells may produce abnormal or inadequate blood cells
describe acute leukaemia
rapidly progressing clonal malignancy of bone marrow/blood with maturation defects
there is an excess of ‘blasts’ >=20%
what is ALL
acute lymphoblastic leukaemia
malignant disease of lymphoblasts (primitive lymphoid cells)
what is the most common childhood cancer
ALL
what are features of ALL
marrow failure: anaemia, thrombocytopaenia, leukopaenia
extramedullary involvement eg testis, CNS
bone pain
what is AML
acute myeloid leukaemia
malignancy of myeloblasts (primitive myeloid cells)
features of AML
disease of the elderly
marrow failure
may be de novo or secondary
what are Auer rods and in which condition are they seen
rod shaped cytoplasmic aggregates of granules
AML
what investigations can be done for leukaemia
FBC Blood film Coagulation screen Bone marrow analysis: - morphology - immunophenotyping with flow cytometry - genetics - trephine
what is needed to make a definitive diagnosis of leukaemia
immunophenotyping with flow cytometry
it can differentiate between AML and ALL
what is the main treatment option for leukaemia
multi agent chemotherapy
how long can treatment last in ALL
up to 2-3 years
describe treatment in AML
intensive, prolonged hospitalisation
2-4 cycles of chemo
what is a Hickman line, what is it used for
central venous catheter CVC
used to administer chemotherapy
what are consequences of bone marrow suppression
Anaemia (reduced erythropoeisis)
Bleeding, bruising, petechiae from thrombocytopaenia
INFECTION from neutropaenia
which type of bacteria can lead to fulminant life threatening sepsis in neutropaenic patients
Gram -ve bacteria
what are other side effects of chemo
N+V hair loss liver/renal dysfunction tumour lysis syndrome infertility cardiomyopathy
what kind of infections are patients prone to with chemo
bacterial - give broad spectrum antibiotics if neutropaenic fever
fungal - if unresponsive to antibiotics
protozoal eg PJP
what is the outcome for patients after chemo
many go into remission
many relapse
some die from treatment related toxicity
