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
acute myeloid leukaemia blood film findings
high proportion of blast cells
can have cytoplasmic inclusions (rods) -> Auer rods
general management of acute leukaemias
multiagent chemo
- hickman line - top of boob, go up under collarbone + into heart
allogenic stem cell transplantation in some, after chemo
chronic lymphocytic leukaemia (CLL)
chronic proliferation of a single type of well differrentiated lymphocyte, usually B lymphocytes
- often asymptomatic
can cause warm autoimmune haemolytic anaemia
can transform into high-grade lymphoma -> Richter’s transformation
chronic lymphocytic leukaemia presentation
often non - picked up on incidental finding of lymphocytosis
weight loss
bleeding, infections
lymphadenopathy more marked than chronic myeloid leukaemia
chronic lymphocytic leukaemia blood findings
count
- lymphocytosis
- anaemia - due to bone marrow replacement or autoimmune haemolytic anaemia (AIHA)
- thrombocytopenia
films
smear / smudge cells occur during the process of preparing the blood film where aged or fragile white blood cells rupture
key investigation in chronic lymphocytic leukaemia
immunophenotyping
smudges on blood film
chronic lymphocytic leukaemia
- involves blood AND lymph nodes
- confirmed by immunophenotyping
- rapidly progressive lymphadenopathy/splenomegaly
asymptomatic -> watch + wait
