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Chronic Leukaemia - Coggle Diagram
Chronic Leukaemia
Chronic lymphocytic
mature b cell neoplasm
clonal proliferation
progressive accumulation of functionally incompetent lymphocytes
monoclonal b cell pop.
single light chain
kappa
lambda
markers
B cell lineage
CD20
usually weak expression
CD23
CD19
CD5
IgHC
mutated
good prognosis
unmutated
poor prognosis
epidemiology
most common leuk. of adults in western
incidence ^ with age
90% over 50yrs
males more
family/genetics
5-10%
Clinical presentation
variable
generally low grade+indolent
asymptomatic
25-50%
fatigue
recurring inf.
lymphadenopathy
85%
splenomegaly
30-50%
hepatomegaly
10-20%
weight loss
loss of appetite
early satiety
petechiae
night sweats
autoimmune complications
AIHA
ITP
Can undergo high grade transformation
Diffuse Large B cell lymphoma
Richter transformation
aggressive
Classic Hodgkin's lymphoma
DX
FBC
^WCC
b lymphocytes >5,000
monoclonal lymphocytosis >3 mths
+/- anaemia
mature lymphocytes
round nuclei
condensed chromatin
scant cytoplasm
broken during prep
smudge cells
Immunophenotyping
Flow cytometry on blood
markers
LN biopsy
Flow cytometry
IHC
Molecular testing
prognosis
clinical course
IGHV mutation status
CD38/ZAP-70 expression
adverse prognostic factors
FISH
+12
shorter survival time
del(13q)
favourable
del(17p)
del(11q)
aggressive
TP53
BM analysis
aspirate
Cell morphology
lymphocytes >30%
flow cytometry
not required for dx
done before treatment
prognosis
trephine biopsy
Clinical course
asymptomatic
bulky LN's
marrow failure
anaemia/thrombocytopenia
richter transformation
Prognosis
indolent not curable
median survival: 10yrs
richter transformation
Rai+ Binet staging systems
extent of disease
presence of cytopenias
Indications for treatment
constitutional symptoms
fever
night sweats
fatigue
weight loss
massive splenomegaly/lymphadenopathy
progressive marrow failure
cytopenias
AIHA/ITP
progressive lymphocytosis
increase>50% in ALC in <2mths or
LDT < 6mths
Treatment
watch and wait unless indicated
Alkylating agents
cyclophsophamide
chlorambucil
bendamustine
purine analogues
fludarabine
pentostatin
Mab's
rituximab
anti-CD20
alemtuzumab
anti-CD52
small molecular inh.
BTK inh.
ibrutinib
PI-3K inh.
duvelisib
Bcl-2 inh.
venetoclax
Allogeneic SCT
younger/high risk patients
Immunosuppression
autoimmune complications
Splenectomy
refractory ITP
haemolysis
combination therapies
FCR
BR
FR
PCR
R-CHOP
Chronic myeloid
clonal proliferation of granulocytic cell lineage
no loss of capacity to differentiate
abnormal pluripotent SC's
arise from t(9;22) translocation
BCR-ABL1 fusion gene
activated oncogene
Chr.22 - philadelphia chr.
constitutively active
proliferation
survival advantage
median age: 50-70
slight male predominance
PATHOGENESIS
translocation in PHSC
proliferates
initial chronic phase
massive expansion
additional mutations
progression to blast phase
66% myeloid cells
33% lymphoid cells
displacement of normal haematopoiesis
chronic-accelerated-blast phase
Clinical Presentation
chronic indolent phase
few symptoms
20-40% asymp. at dx
fatigue
weight loss
low grade fever
sweating
splenomegaly
abd fullness
LUQ abd. pain
hepatomegaly
accelerated/blast phase
impaired marrow function
anaemia
non-functioning white cell blasts
inf.
thrombocytopenia
bleeding
petechiae/ecchymoses
basophilia
bone pain
DX
FBC
^WBC
50,000-200,000
granulocytosis with left shift
immature granulocytes
bands
metamyelocytes
myelocytes
thrombocytosis
becomes thrombocytopenia
+/- anaemia
peripheral smear
immature granulocytes at different stages of maturation
BM analysis
cell morphology
hypercellular
myeloid cell expansion
aspirate
cytogenetics
Ph chr.
karyotype
FISH
PCR
BCR-ABL1 fusion
Immunophenotyping
flow cytometry
bm aspirate
blast lineage determination
accelerated/blast phase
IHC
trephine
assess for increased and/or clustered blasts
Confirm t(9;22) / BCR-ABL fusion
minimal residual disease monitoring
RT-PCR
MMR= 3 log decrease from baseline
ABL1 kinase domain mutation analysis
mutations that decrease TKI effectiveness
Treatment
Imatinib
inh. BCR-ABL
resistance can develop
2nd gen. TKI
nilotinib
dasatinib
bosutinib
3rd gen
ponatinib
asciminib
targets myristoyl pocket
adults in chronic phase
previously treated with 2/more TKI's
new 3rd/4th gen
olverembatinib
vodobatinib
PF-114
Omacetaxine
protein translation inh.
blocks protein synthesis
chronic/accelerated phase
resistant/intolerant to 2/more TKI's
Approach
1st line
imatinib
nilotinib
dasatinib
monitor response
rising transcript level
disease progression
ABL1 kinase domain mutation analysis
change of TKI
T315I mutation
ponatinib
asciminib
failure of TKI's
2nd/3rd therapy
allogeneic SCT
curative
risky
General
mature/more differentiated cells
bone marrow exam
aspirate
cell morphology
enumeration of marrow cellular elements
trephine biopsy
cell morphology
fibrosis
marrow architecture
vasculature
infections
infiltrative disorders
Histopathology
cellularity
hyper
hypo
normal
presence of trilinear maturation?
myeloid:erythroid ratio
normal=3-4:1
abnormalities of haematopoietic elements
iron stores
ringed sideroblasts?
fibrosis
vascular abnormalities
bone
presence of infiltrate
Immunophenotyping
Flow cyt.
aspirate
IHC
trephine
Cytogenetics
karyotype
FISH
aspirate
Further tests
PCR
NGS