Haematological malignancies Flashcards
AML OVERVIEW
i) which group is it the most common acute leukaemia in?
ii) what can it be a result of?
iii) what cells will be seen on blood film? what feature may they have?
i) adults
ii) result of transformation from a myeloproliferative disorder eg PCV or MF
AML FEATURES
i) name two ways a patient may present? how is it diagnosed? how is it confirmed?
ii) name five clinical features that may be seen
iii) name four techniques that are used in diagnosis
i) px with pancytopenia or leucostatsis (vasc obstruction with WC plug) if high WCC
Dx by pres of blasts on blood film
confirmed by BM biopsy
ii) anaemia, infections, DIC, ulcers, infiltration, bruising
iii) morphology, immunophenotyping, cytogenetic, molecular (FLT3, DNMT3A)
AML MX
i) what is the overall cure rate? what does prognosis depend on?
ii) what treatment is given? what tx is potentially curative?
iii) name three poor prognostic features
i) overall cure <30%
prognosis dep on cytogenetics and gene mutations
ii) intensive chemo DA 3+10 regimen
allogeneic SCT are potentially curative
iii) >60yrs, >20% blasts after first course of chemo, cytogenetics (deletion of chr 5 or 7)
ALL overview
i) who is it the most common cancer in? what is peak age? what syndrome can it be associated with?
ii) where is the malignant change? what does it cause? how does this lead to pancytopenia?
iii) what translocation may be seen?
iv) what does the blood film show
v) what is the cure rate? which rearrangement is often seen in adults with ALL?
i) most common cancer in children aged 2-4yrs - also assoc with downs syndrome
ii) malignant change in in a lymphocyte precursor > causes an acute proliferation of a single type of lympho (usually B lympho)
excess prolif > replace all other cell types in the BM leading to pancytopenia
iii) may see T 9;22 - philadelphia chromosome
iv) blood film shows blast cells
v) cure rate is >90%
worse prognosis in adults with BCR-ABL rearrnagement
ALL DX AND MX
i) how may it present in children? (3) what is seen on blood film? (2)
ii) which type is more common with better prognosis? which type is usually assoc with a mediastinal mass due to LNs?
iii) name four techniques used to dx
iv) how long is chemo given for? what are the three phases of tx? what is monitored to determine optimal tx?
v) name three long term problems survivors may have?
i) failure to thrive, lymphadenopathy and anaemia
see lymphocytosis and blasts on blood film
ii) B cell is more common with better prog and T cell is usually assoc with mediastinal mass
iii) BM biopsy, flow cyto, cytogenetics, molecular analysis
iv) chemo for 2 years - induction, consolidation, maintenance
monitor minimal residual disease to det optimal tx
v) infertility, endocrine, psychological, secondary cancers
CHRONIC MYELOID LEUKAEMIA OVERVIEW
i) what happens in the three phases of disease - chronic/accelerated/blast phase
ii) which cytogenetic change is charac of CML? which translocation is this? what abnormal fusion protein does it produce
i) chronic phase - can last up to 5 years and is often asymp, pts dx incidentally with raised WCC
accelerated phase - abnormal blast cells make up high prop of cells in BM/blood (10-20%) - pt becomes more symptomatic, dev anaemia/thrombocytopenia and may be immunocomp
blast phase - abnormal blasts take up a high proportion of blast cells and blood (>30%) see severe pancytopenia - often fatal
ii) see philadelphia chromo - 9;22 transloc
BCR-ABL fusion
CML MX
i) which cells are too high? what can this cause? what organ is enlarged?
ii) how is it treated? how does this work?
i) too many granulocytes (high WCC) which can cause leucostasis
massive splenomegaly
ii) tx with imatinib (gleevec) - inhibits ATP pocket in BCR-ABL > substrate cant bind and tumour cell cant proliferate
CHRONIC LYMPHOCYTIC LEUKAEMIA OVERVIEW
i) what happens? which cells are usually involved?
ii) over which age are patients usually? how may it present? (3) what type of haemolytic anaemia can it cause?
iii) what can it transform into? what is this called?
iv) what does blood film show? why does htis happen
i) chronic proliferation of a single type of well differentiated lymphocyte (usually B lymphos)
ii) pts usually >55yrs
often asymp but can px with infections, anaemia, bleeding and weight loss
can cause wam AI haemolytic anaemia
iii) can transform into high grade lymphoma (richters transformation)
iv) blood film shows smear or smudge cells - occurs during process of prep blood film where aged or fragile WVC rupture and leave a smudge on the film
CLL
i) what lymphocyte levels are seen? which two other organs are enlarged?
ii) which two technques are used to dx? what staging system is used?
iii) what is mx det by? what mutation status can also det prognosis?
i) high lymphocyte count >10
see splenomegaly and lymphadenopathy
ii) morphology and immunophenotyping
staging using binet staging system
iii) mx det by p53 mutant or 17p deletion
prognosis also det by IgVH status
CLL MX
i) when is tx indicated?
ii) what is first line if p53 WT?
iii) what is given if p53 is mutated, deleted or there is progression? give three examples?
iv) what can be given if CLL is complicated with AIHA or Immune thrombocytopenia
i) tx if BM failure (cytopenia)
ii) p53 WT - chemo immuno FCR (fludarabine, cyclo, rituxmab)
iii) p53 mut - use targeted therapy
ibrutinib (oral BTK inhibitor), venetoclax (BCL2 inhibitor), idealisib (PI3K inhibitor)
iv) tx with steroids
MYELOMA OVERVIEW
i) what cells are implicated? what is produced? what is the most common Ig found? what is this AKA
ii) what is MGUS? how is it usually found?
iii) what is SMM? which type of SMM has an excess of IgM?
iv) what can be found in urine of patients with myeloma? what is it?
i) implicates plasma cells (B lymphos) > mut causes rapid and uncontrollable multiplication and produce one type of antibody (Ig)
most produce IgG = monoclonal paraprotein (single antibody prod by all cancerous plas cells)
ii) MGUS = excess of a single type of antibody/ab prod without other features of myeloma (often incidental finding)
iii) SMM us progression from MGUS with higher levels in antibodies (pre malignant)
waldenstroms macroglobilinaemia is SMM with excess IgM
iv) bence jones protein found in urine = subunit of antibody called light chain
MYELOMA PATHOPHYS
i) why do patients become anaemic?
ii) name three reasons why patients develop renal disease
iii) how is plasma viscosity affected in myeloma? why? name four problems this may cause
iv) name four risk factors
v) what are the two main types of antibody found? which has a better prognosis? what are 15% of these?
i) BM infiltration of plasma cells > supressed dev of other blood cells
ii) high levels of Ig that block flow through tubules, hypercalc impairs renal func, dehydration, medication eg bisphos can impair kidney func
iii) increased plasma viscosity due to high levels of Ig in blood > easy bruising, bleeding, reduced/loss sight, purple extremities (purplish palmar erythema), heart failure
iv) older age, male, black african, FH, obesity
v) IgG and IgA (IgG has better prognosis) 15% are light chain only (kappa and lambda)
MYELOMA BONE DISEASE
I) which type of bone cells are inc and which are decreased in bone disease? what does this result in? what is this caused by in relation to plasma cells?
ii) name three common places for myeloma bone disease to occur
iii) what are the resulting thin areas of bone called? what does this lead to?
iv) how is calcium implicated?
v) which type of tumours can manifest in the bone?
i) increased osteoclast activity abd decreased osteoblast activity = more bone resorption than construction
caused by cytokines released from plasma cells and stromal cells when in contact with plasma cells (IL-1)
ii) skull, spine, long bones, ribs
iii) thin areas = osteolytic lesions > leads to pathological fractures
iv) increased osteoclast activity causes lots of calcium to resorbed from bone into the blood > hypercalcaemia
v) dev of plasmocytomas > occ in bones and replace normal tissue
MYELOMA INVESTIGATIONS
i) in which situation should myeloma be considered?
ii) name four bloods that should be done? name two other special tests that can be done
iii) which tests should all be done when myeloma is suspected? (BLIP) what test is necessary to confirm?
iv) name three imaging tests that may be done to assess for bone lesions? mame three signs seen on xray?
v) what measure is useful in dx and monitoring disease? what is seen?
vi) what is the freelite test? what does it detect?
i) anyone over 60 with persistent bone pain (back pain) or unexplained fractures
ii) FBC (low WCC), calcium (raised, ESR (raised), plasma viscosity (raised)
also do serum protein electrophoresis and urine bence jones protein test
iii) Bence jones prot (urine electro), Light chain assay, Immunoglobs, Protein electrophoresis of serum
BM biopsy to confirm
iv) whole body MRI, CT or skeletal survey (xray of whole skeleton)
X ray - punched out lesions, lytic lesions, raindrop skull (caused by punch out lesions through skull > raindrops splashing on surface)
v) paraprotein (monoclonal Ig) > ident by serum protein electrophoresis - sep proteins by electrical charge > see M band
vi) freelite test aka serum free light chain assay > det bence jones protein in serum
measures kappa and lambda light chain (ratio is key)
MYELOMA MANAGEMENT
i) what is the aim of tx?
ii) what is first line tx? (3) what may also be done?
iii) what do all patients require when on chemo?
iv) how can myeloma bone disease be managed medically? name three other things that can be done
v) name four complications of myeloma/treatments
i) aim is to control disease
ii) chemo - borezomid, thalidomide, dex
can also do SCT
iii) all pts req VTE prophylaxis with aspirin or LMWH
iv) use bishphos to supress osteoclast activity
RT to improve bone pain
orhtopaedic sx to stablise bones
cement augmentation > inject cement into verebral fractures or lesions to improve stability
v) infection, pain, renal fail, anaemia, hyperaclc, periph neuropathy, sp cord compress, hyperviscosity
