haematological malignancies + leukaemia Flashcards
what is malignant haemopoiesis usually characterised by?
increased number of abnormal + dysfunctional cells, loss of normal activity, due to 1 or more of -
- increased proliferation (in the absence of a stimulus)
- lack of differentiation/maturation
- lack of apoptosis
haemopoiesis - acute leukaemias/marrow based malignancies
immune functions - certain lymphomas
what causes haematological malignancies?
genetic, epigenetic, environmental interaction
ACQUIRED somatic mutations in regulatory genes
- driver mutations vs passenger mutations
usually multiple “hits”
driver mutations
driver mutations can select “clones”
clone = popultation of cells derived from a single parent cell
- this parent cells has a genetic marker (driver mutation or chromosomal change) that is shared by the daughter cells
- clones can diversify but contain a similar genetic “backbone”
normal haemopoiesis = polyclonal
malignant haemopoesis = monoclonal
genetic journey toward a cancer phenotype
driver mutations -> confer growth advantage on the cells + are selected during the evolution of the cancer
passenger mutations -> DO NOT confer growth advantage, but happened to be present in an ancestor of the cancer cell when it acquired one of its drivers
type of haematological malignancies
- based on lineage - myeloid vs lymphoid
- based on developmental stage (precursor) within lineage
- more relevant in lymphoid (myeloid affect more primitive progenitor or stem cell compartments)
—more primitive B cell progenitors -> ALL
—more mature B cell lymphocyte pool -> CLL
—more mature, plasma cells -> myeloma - based on anatomical site involved
- blood -> leukaemia
- lymph node -> lymphoma
(CLL can involve both)
(myeloma = plasma cell malignancy in marrow)
signs of histological aggression
- large cells with high nuclear-cytoplasmic ratio
- prominent nuclieoli
- rapid proliferation
age of leukaemia presentation
ALL CeLLmates have CoMmon AMbitions
o <5 + over 45 -> Acute Lymphoblastic Leukaemia
o Over 55 -> Chronic Lymphocytic Leukaemia
o Over 65 -> Chronic Myeloid leukaemia
o Over 75 -> Acute Myeloid leukaemia
why can leukaemia cause a pancytopenia?
the excessive production of a single type of cell can lead to suppression of other cell lines causing underproduction of other cell types
–> pancytopenia
common presentation to all leukaemias
fatigue, fever, failure to thrive (kids)
pallor - anaemia
petechiae + abnormal bruising - thrombocytopenia
infections - neutropenia
abnormal bleeding
lymphadenopathy
hepatosplenomegaly
acute leukaemia
rapidly progressing clonal malignancy of marrow/blood with maturation defects
- defined as an excess of “blasts” (>=20%) in either peripheral blood or bone marrow
- decrease/loss of normal haemopoeitic reserve
acute leukaemia investigations
blood count/film
- pancytopenia
- WCC elevated on blood film
- presence of blasts, agressive histological features
coagulation screen
bone marrow aspirate
- morphology - monotonous (same look) population
- immunophenotype (by flow cytometry) - to work out lineage, definitive diagnosis !!
complications of chemo
N+V, hairloss
liver, renal dysfunction
tumour lysis syndrome - during first coure of treatment
infections
problems with marrow suppression - anaemia, neutropenia, thrombocytopenia
late effects
- loss of fertility
- cardiomyopathy with anthracyclines
acute lymphoblastic leukaemia (ALL)
malignant disease of primitive lymphoid cells (lymphoblasts)
- usually b lymphocytes
- excessive proliferation, they replace others -> pancytopenia
commonest childhood cancer - peaks 2-4yrs + adults over 45
assoc with downs syndrome
acute lymphoblastic leukaemia (ALL) presentation
marrow failure - anaemia, infections, bleeding
high count with obstruction of circulation
**involvement of areas outside the marrow + blood (extra-medullary) - CNS, testis
blood film -> blast cells
acute myeloid leukaemia
more common in elderly (>60yrs)
may be “de novo” or secondary
presentation similar to ALL (marrow failure)
sub groups of AML presentation
- coagulation defect -> DIC in acute promyelocytic leukaemia
- gum infiltration (in other types)
can be secondary to myeloproliferative disorder - polycythaemia ruby vera, myelofibrosis
