MedEd Haem 1 Flashcards
name myeloid cells
RBCs
mast cells
basophils / neutrophils / eosinophils
platelets
PC of acute leukaemias
anaemia
thrombocytopaenia
neutropenia
(pancytopaenia)
bone pain
fever
which type of leukaemia has splenomegaly
chronic > acute
PC of chronic leukaemias
lymphadenopathy
splenomegaly
why does chronic leukaemia not have same Sx as acute
chronic is slower proliferation of malignant cells
less burden of disease in BM in chronic
what is the leukaemia emergency
leukostasis
what is leukostasis
EMERGENCY
high WCC –> increased viscosity of blood –> end organ damage
PC of leukostasis
retinopathy
pulmonary infiltrates
bleeding
thrombosis
Tx of leukostasis
leukaphoresis
chemo
steroids
which type of leukaemia is leukostasis common / uncommon
AML common
then ALL / CML
CLL unusual
in what type of leukaemia can pts be asymptomatic
CLL
classical Hx of ALL
2-5 y/o child
hepatosplenomegaly
bone pain / limp
fevers
what % of pts have CNS disease in ALL
10%
what sign is rare but very specific to ALL in boys
testicular swelling
how do adults present with ALL
similar to AML
lymphadenopathy
BTs and results of ALL
FBC
thrombocytopaenia
anaemia
high WCC but low neutrophils
film - blasts in peripheral blood
can circulating blast cells be normal
NO - indicates leukaemia or a few other conditions
features of blast cells on blood film
high nucelus:cytoplasm ratio
larger than RBCs (normal lymphocytes are same size as RBCs)
what cell shape is indicative of ALL vs AML
‘hand mirror’/’table tennis bat’ shaped
how is ALL Dx
BM biopsy
flow cytometry
(hard to tell AML from ALL on blood film)
what markers are typically present in ALL flow cytometry and what do they indicate
TdT+ / CD34+ (immature cell marker)
CD19 (B cell marker)
CD3 (T cell marker)
what genetic mutation causes ALL in 20-30% of adults
BCR-ABL1 t(9;22)
(also causes CML)
Tx of ALL
chemo
transplant of BM
RFs for AML
incidence increasing with age
previous history of myelodysplastic syndrome / chemo
BTs and results of AML
FBC - anaemia, thrombocytopaenia, high WCC, low neutrophils
film - high blasts
normal or high INR
blood film of AML
auer rods (stick in the lymphocytes)
what % of AML has auer rods
20-30%
flow cytometry markers present in AML
MPO CD34
CD13 / 33 / 117
(xs detail but may come up)
Tx of AML
chemo - shorter duration than ALL
PC of APML (acute promyelocytic leukaemia)
DIC - inc intracranial bleeding
good prognosis after induction
Tx of APML
ATRA (vitamin A)
all trans retinoic acid
which of these is most concerning for acute leukaemia?
neutrophils 12
10cm splenomegaly
microcytic anaemia
blast cells on blood film
cervical lymphadenopathy
blast cells on blood film
what are myeloproliferative neoplasms (MPNs)
increased production of myeloid lineage
what can cause a high platelet count (in order of most common)
acute infection
chronic inflammatiom
malignancy (5-10%)
essential thrombocytopaenia
polycythaemia rubra vera
what is ET
platelet count >450 consistently with no other cause
complications of ET
thrombotic events arterial / venous
small risk transformation to myelofibrosis / AML
what mutations are present in ET
JAK2 55%
CALR / MPL in most other pts
Tx of ET
aspirin - reduce stroke risk
hydroxycarbamide - lower platelets
what is PCV
polycthaemia rubra vera
overproduction of RBCs
Hct levels of PCV in men / women
men >0.52
women >0.48
complications of PCV
high risk thrombotic events eg stroke
Budd Chiari (hepatic vein thrombosis)
risk of transformation to MF / AML
what mutation do 95% of PCV pts have
JAK2
TX of PCV
aspirin - reduce stroke risk
venesection - lower Hct
hydroxycarbamide - lower plts
causes of high HCt
PCRV
altitude
chronic hypoxia - severe COPD / cyantoic heart disease / OSA
erythropoeitin secreting renal cancers
what is myelofibrosis
clonal proliferation of stem cells in BM. also overproduction of cytokines that cause fibrosis of BM –> reduced production of all cell lineages.
complications of myelofibrosis
risk of transformation to AML
what conditions can develop into myelofibrosis
ET
PCV
mutations causing myelofibrosis
JAK2 50%
CALR
2 buzzwords for myelofibrosis
‘dry tap’ on BM aspirate
‘tear drop poikilocytes’ on blood film
Tx of myelofibrosis
stem cell transplant
ruloxitinib - JAK inhibitor
name 4 myeloproliferative neoplasms
essential thrombocytopaenia
polycythaemia vera
myelofibrosis
CML
typical history of CML
35-55 y/o
LUQ pain with splenomegaly
asymptomatic if in chronic phase
FLAWS OR acute leukaemia Sx if in blast phase (10%)
3 key causes of splenogemaly
CML
myelofibrosis
leishmaniasis
BTs of CML and results
FBC - anaemia, high WCC, normal or high platelet count, neutrophillia, may have elevated basophils, low monocyte count
film - precursor cells (maybe)
other causes of high basophil count
worry about CML !! not much other causes
causes of high WCC with which cell in particular would be raised in each
acute bacterial infection - neutrophils high
acute viral infection - lymphocytes high
fungal / parasitic infection - eosinophils high
TB / endocarditis / inflammation - high monocytes
another cause of increase precursor cells on film
severe acute infections
elevated basophil and eosinophils
CML !!
blood film features of CML
left shift (more precursors)
leukocytosis
eosinophils
basophilia
hypoblasted megakaryocytes
how is CML Dx
almost all with philadelphia chromosome (BCR - ABL1 t(9;22)) using FISH
phases of CML
chronic 85-90%
accelerated (recently removed from classification but increasing number of blasts in BM)
blast phase - >20% blasts in BM, PC like acute leukaemia
Tx of CML
tyrosine kinase inhibitors (eg imatinib)
survival of CML
> 90% 10 year survival
PC of CLL
asymptomatic
high WCC
>50 y/o M>F
some have small lymphadenopathy / splenomegaly
some present with ITP / haemolytic anaemia
BTs of CLL and results
FBC - normal Hb, high WCC usually >100, normal plts, normal neutrophils, high lymphocyte count
what does anaemia at presentation in CLL indicate
more aggressive disease or haemolytic anaemia
blood film of CLL
smear / smudge cells - BUZZWORD
lymphocytosis
Dx of CLL
flow cytometry
- immunophenotyping for clonal population of cells
- same cell markers eg kappa/lamba light chains
what disease has same pathology as CLL but different distribution
small lymphocytic lymphoma
- blood / marrow vs lymph nodes
how is CLL staged and how does this determine Tx
Binet staging
- A = no cytopaenia, <3 areas of lymphoid involvement
- B = no cytopaenia, 3+ areas of lymphoid involvement
- C = cytopaenia
A = watch and wait
B = consider Tx
C = Tx
what aggressive condition can CLL transform into
Richters syndrome
Tx of CLL and what does it depend on
if IGHV mutated = rituximab + chemo eg FCR
if TP53 mutated = BTK inhibitors eg ibrutinib
can use venetoclax (BCL2 inhibitor)
causes of pancytopaenia
b12 / folate deficiency
medications - co-trimoxazole / linezolid
cancer - acute leukaemia, BM mets
aplastic anaemia - eg due to sepsis / AID / parvovirus b19
myelodysplastic syndromes
myelofibrosis
what blast % would diagnose acute leukaemia
> 20%
what is myelodysplastic syndrome
dysplatic changes (abnormal cells) in 1 or more myeloid cell lines (erythroid, megakaryocytes, granulocytes)
PC of myelodysplastic syndrome
asymptomatic
incidental cytopaenia
what can myelodysplastic syndrome progress to
AML
characterise the anaemia in MDS
macrocytic anaemia
normal b12 / folate levels
blood film of MDS - buzzwords
pseudo-pelger anomaly
bilobed neutrophils
ring sideroblasts
4 prognostic factors for MDS
number /extent of cytopaenias
BM blast % (>20 = AML)
cytogenetic changes
specific mutations eg TP53 (poor)
what % of MDS progress to AML
30%
how is risk of progression to AML from MDS assessed
IPSS-R / IPSS-M
Tx of MDS
higher risk - chemo
younger pts - stem cell transplant
contrast age peak of HL and NHL
HL = young
NHL = increases with age
contrast lymph node involvement in HL and NHL
HL = mediastinum mainly. painful on drinking alcohol
NHL = anywhere
contrast course and prognosis of HL and NHL
HL = aggressive but mostly curable
NHL = variable course and prognosis
roughly how are lymphomas categorised
HL or NHL
of NHL - B cell or T cell
(just 4 types of HL)
of B cell - subtypes eg Burkitts / mantle cell / follicular / DLBCL
(T cell is basically just ATLL)
most common subtypes of lymphomas
NHL > HL
B cell > T cell
which types of lymphomas are low grade
follicular B cell
which types of lymphomas are high grade
diffuse large b cell lymphoma
burkitt’s (++++ high grade)
staging of lymphoma
Ann-Arbour
1 = one nodal group
2 = 2+ nodal groups all same side of diaphgram
3 = 2+ nodal groups on both side of diaphragm
4 = infiltration of another organ that isn’t LN
A = no B Sx present
B = B Sx present
age peaks of HL
bimodal
mainly <30 but also peak in 70s
PC of HL
B Sx with lymphadenopathy (mediastinal, worse after alcohol)
Dx feature of HL on blood film
reed - sternburg cells (BUZZWORD)
- large cell with 2+ nucleus
- may only see 1 per LN, still diagnostic
most common type of HL
nodular sclerosing
what is HL associated with
EBV
Tx of HL
ABVD chemo + radio
stem cell transplant if Tx fails
prognosis of HL
good chance of cure
age peak of NHL
unimodal
75-85
most common subtype of NHL
b cell > t cell
PC of NHL
B Sx or lymphadenopathy
most common indolent NHL
follicular
name another indolent NHL that is similar to CLL but with disease in nodes
small lymphocytic lymphoma
how do indolent NHL present
very large lymphadenopathy
risk of indolent lymphoma
transformation to high grade
what is seen on lymph node biopsy of follicular lymphoma
large number of centroblasts
Tx of follicular lymphoma
watchful waiting unless high burden of disease
cause of follicular lymphoma
t(14;18) causing fusion of BCL2 gene
how does the course of indolent lymphomas vary from high grade
indolent - often have relapsing remitting
high grade - more aggressive but once cured, they won’t come back
most common high grade lymphoma
diffuse large b cell
PC of diffuse large b cell lymphoma + one association
lymphadenopathy, B Sx +/- BM involvement
can be associated with EBV
risk of Tx of diffuse large b cell lymphoma
tumour lysis syndrome
name another high grade lymphoma
mantle cell (may have leukaemic phase)
cause of mantle cell lymphoma
t(11;14) –> overexpression of cyclin d1
Tx of mantle cell lymphoma
chemo
blood film of mantle cell lymphoma
cleft in mantle cell - nucleus looks like a heart
tx of diffuse large b cell
R-CHOP (rituximab-CHOP) chemo
name the most common very high grade lymphoma
burkitts
PC of burkitts
very fast growing lump in lymph nodes of neck / abdo
risk of tx with burkitts
tumour lysis syndrome ++
histology buzzword of burkitts
starry sky apperance
(bright white pearly vacuoles in blue cells)
associations of burkitts
EBV / HIV
t(8;14)
who gets burkitts
younger adults
2 examples of T cell lymphoma with a common feature of each
ATLL (adult t cell lymphoma) - flower cells on blood film
cutaneous T cell lymphoma - rare, PC = weird rashes
who gets ATLL
ppl from far east
tumour lysis syndrome results
high creatinine / urea
high K
high PO43
high uric acid
low Ca
Tx of tumour lysis syndrome
rasburicase
renal replacement therapy
medication to prevent tumour lysis sydrome
allopurinol
rasburicase if high risk
how does rasburicase work in TLS
depletes uric acid levels
what is multiple myeloma
clonal population of plasma cells which proliferate and produce monoclonal Ig light chains
diagnostic finding of multiple myeloma in blood / urine (buzzwords)
blood = paraprotein
urine = bence jones protein
describe the progression to myeloma
MGUS –> MM
MGUS –> smouldering myelome –> MM
diagnosis criteria of myeloma
clonal BM plasma cells >10% in marrow or plasmacytoma
PLUS
end organ damage - indicated by 1+ of CRABS:
Calcium >2.75
Renal - creatinine >177 / creatinine clearance <40ml/min
Anaemia - Hb <100
Bone lesions - lytic lesions
SLIM - >60% plasma cells in BM / light chain ratio >100, MRI lesions
what is smouldering myeloma
aka asymptomatic myeloma
serum monoclonal protein (IgG or IgA) >30g/L OR bence jones protein
AND / OR
clonal BM plasma cells 10-60% in marrow
+ NO end organ damage !!
progression of smouldering myeloma
most will progress to myeloma if untreated
no point treating them tho unless they become myeloma
what does MGUS stand for
monoclonal gammopathy of unknown significance
features of MGUS
serum monoclonal protein <30g/L
plasma cells <10% in BM
no end organ damage
no evidence of another disorder
what % of MGUS progress to myeloma every year
1-2%
who gets MGUS
very common in elderly
what % of SM progress to myeloma every year
10%
paraprotein level of MGUS / SM / MM
MGUS <30
SM >30
MM = ANY but usually >30
plasma cell % in BM of of MGUS / SM / MM
MGUS <10%
SM 10-60%
MM >10%
which type of myeloma is the only to have CRAB Sx (end organ damage) and MRI lesions
MM
free light chain ratio of of MGUS / SM / MM
MGUS <100
SM <100
MM >100
what rare condition is similar to myeloma but with a few key differences
waldenstrom’s macroglobulinaemia
key differences between waldenstrom’s macroglobulinaemia and myeloma
in waldenstroms:
- paraprotein is always IgM
- present with lymphadenopathy (similar to follicular lymphoma) and not CRAB Sx
- abnormality in lymphoplasmatoid cells as well as plasma cells
- high risk of hyperviscosity syndrome
blood film features of myeloma
rouleaux - stacking of RBCs
plasma cells in peripheral blood
Mx of MGUS
annual blood test
Mx of smouldering myeloma
3 monthly review to detect progression to myeloma
Tx of myeloma inc older / younger / baseline tx
autologous stem cell transplant - esp in younger ppl
chemo - older ppl
initial tx - proteasome inhibitors, dexamethasone, thalidomide
Ix for a well man with paraprotein >10
refer to haematology !
imaging to look for bone lesions
BM biopsy
55M PC fatigue.
BTs - Anaemia
serum electrophoresis = IgG kappa paraprotein 37.
BM aspirate = clonal population of plasma cells, 15% of marrow cells
Dx?
multiple myeloma
- if paraprotein >30, then it can only be SM or MM.
- Presence of anaemia (CRAB Sx) = only MM.
55M 2/52 fatigue and easy bruising.
BTs - high WCC, anaemia, low plts.
blood film - blasts, 27% blasts in BM
flow cytometry - clonal population of cells CD34+, CD19+, TdT+
cytogenetic analysis - t(9;22)
Dx?
ALL
- >20% blasts in BM = acute leukaemia.
- CD19+ = B cell marker. TdT = B cell pre-cursor marker
- t(9;22) is CML or ALL
25M drenching night sweats.
BTs - normal ish
LN biopsy - multinucleated cell, very large.
Dx?
HL
- multinucleated cell = reed sternburg cell
50F splenomegaly.
high WCC
blood film = left shifted granulocytes.
FISH = BCR-ABL1 fusion gene
Dx?
CML
- splenogemaly = CML or myelofibrosis or leishmaniasis
- high WCC = more likely CML or myelofibrosis
- left shift = favours CML
- BCR-ABL1 = diagnostic of CML
