Cancer - Haematology Flashcards
name the myeloid malignancies
acute myeloid leukaemia
chronic myeloproliferative neoplasms
name the lymphoid malignancies
acute lymphoblastic leukaemia
chronic lymphocytic leukaemia
lymphoma
symptoms of bone marrow failure
anaemia
thrombocytopaenia
neutropenia
(pancytopenia)
symptoms of disease involvement in heam malignancies
lumps
organomegaly
any site
systemic symptoms in heam amlignancy
unintentional weight loss
drenching night sweats
fevers
pruritis
what blood tests do you do when ivnestigating a heam malignancy?
FBC, U+Es, LFT, CRP, Ca2+
heamtinics, retics, blood film
LDH, urate, B2M, PV+
If +/- SFLC
PB immunophenotyping
what imaging would be done when investigating haem malignancy?
CT scan
PET scan (lymphoma/myeloma)
MRI spine/pelvis (myeloma)
invasive investigations to be done when investigatings haem malignancy?
tissue biopsy
BM aspirate and trephine
name the chronic myeloproliferative neoplasms?
red cells: polycythaemia
platelets: thrombocythaemia
white: CML (leukaemia)
myeloid cells: primary myelofibrosis
what is acute lymphoblastic leukaemia?
malignancy of the lymphoid cells affecting B or T cells with uncontrolled proliferation of immature blast cells
clincial features in a pt with ALL?
anaemia: lethargy, pallor, dyspnoea, syncope
neutropenia: frequent, severe, opportunistic infections
thrombocytopenia: bruising, petechiae
- bone pain
- lymphadenopathy
- splenomegaly
- hepatomegaly
- fever (present in 50%)
- testicular pain
- CNS involvment (CN palsies, meningism)
Ix to do in a pt with suspected ALL?
blood film: characteristic blast cells
FBC: WCC count usually high
CXR and CT: mediastinum and abdo lymphadenopathy
bone marrow: hypercellular with >20% leukaemic blasts
LP to assess CNS involvement
supportive Mx of ALL + AML ?
- blood/platelet transfusion
- IV fluids
- allopurinol: prevent tumour lysis syndrome
- prophylactic abx (high risk of neutropenic sepsis)
- insert port system/hickman line
Tx of ALL?
inducing remission: vincristine, prednis, l-asparaginase + daunorubicin (ALL violent ppl love drugs)
CNS prophylaxis: intra-thecal/ IV methotrex
miantenance: prolonged chemo agents for 2 years
marrow transplant: match related and once in 1st remission = best option
what is remission defined as in ALL?
no evidence of leukaemia in blood, normal recoverign blood count and <5% blasts in normal regeneratign marrow
classic presentation of ALL?
- 80% of childhood leukamia
- peak incidence around 2-5yo, 75% of cases below age 6
- boys>girls
- associated with downs
poor prognosis factors for ALL?
- less than 2 or older than 10
- WBC >20
- T or B cell surface markers
- non caucasion
- male
- philadelphia chromosome
what are blast cells?
early heamopoietic cells (immature) that accumulate in the bone marrow in leukaemia
what age is AML most common in?
median onset at 65 years (most common form of acute leukaemia in adults)
what are the clinical features of AML?
- bone marrow failure
- neutropenia: infections
- bleeding, bruising, petechiae (from thrombocytopenia + DIC)
- anaemia: fatigue, pallor, syncope
- gum hypertrophy + infiltration
- skin involvement + CNS disease
Tx in AML?
5 cycles of chemo given in 1 wk blocks to induce remission (Daunorubicin and cytarabine)
marrow transplant (for refractory or relapsing disease):
methotrexate given to prevent rejection
what are teh 3 phases of CML and how do they present?
chronic: last 5 yrs, asymptomatic, pts have high WCC
accelerated: occurs when blast cells take up 10-20% of marrow, become asymptomatic -> anaemia, thrombocytopaenia, immune compromised
blast phase: 30% of cells are blast cells causing pancytopaenia, often fatal
peak age of CML?
age 50-60
more common in males
characteristic feature of CML in karotyping?
translocation between chromosomes 9 and 22: presence of philadelphia chromosome (present in >80% CML cases)
clinical features of CML?
(chronic and insidious)
- weight loss, anorexia, night sweats
- splenomegaly
- anaemia: pallor, dyspnoea, tachy, tiredness
- thrombocytopaenia: bleeding, bruising
- gout features due to hyperuricaemia
Ix to diagnose CML?
- fbc: wcc massively increased
- raised neutrophils, monocytes, basophils, eosinophils
- low hb
- u+es: high urate levels
- raised b12
- bone marro biopsy - hypercellular
- cytogenic analysis
Mx of CML?
imatinib (tyrosine kinase inhibitor) = 1st line
other: hydroxyurea, interferon-alpha, allogenic bone marrow transplant
what are the genetic mutations that lead to myeloproliferative disorders
PV -> JAK2
essential thrombocythaemia -> JAK2, CALR, MPL
primary myelofibrosis -> JAK2, CALR, MPL
clinical features of polycythaemia vera?
result from hyperviscosity, hypervolaemia, hypermetabolism or thrombosis:
- headaches, dyspnoea, blurred vision, night sweats, pruritus
- plethoric apperance, ruddy cyanosis, conjuctival suffusion
- splenomegaly
- gout
- heamorrhage or thrombosis
what blood findings wld you see in polycythaemia vera?
raised heamoglobin
marrow biopsy
genetic testing - looks for JAK2 mutation
Tx for polycythaemia vera?
- venesection
- aspirin
- chemotherapy
what is essential thrombocythaemia?
raised platelet count due to megakaryocyte proliferation
clinical features of essential thrombycythaemia
thrombosis and haemorrhage
however most picked up on routine blood tests
how is a diagnosis of essential thrombocythaemia made?
- platelet count >450
- presence of acquired mutation (JAK2, CALR)
- no other myeloid malignancy, PV, primary myelofibrosis, chronic myeloid leukaemia, or myelodysplastic syndrome
- no reactive cause + normal iron stores
- bone marrow trephine histology shows increased megakaryocytes
diagnosis: 1-3 or 1 + 3-5
treatment for essential thrombocythaemia?
aspirin in low risk (<40yo)
hydroxycarbamide in high risk (>60yo, thrombosis risk high, platelet count >1500)
what is primary myelofibrosis?
proliferation of cell line leads to fibrosis of bone marrow - marrow replaced by scar tissue as a response to cytokines
haematopoesis then occurs in spleen = splenomegaly
clinical features of primary myelofibrosis?
anaemia symptoms
splenomegaly with abdo discomfort, pain w/ portal HTN
weight loss, anorexia, fever, night sweats
bleeding
bone pain
gout
diagnosis of primary myelofibrosis?
fbc - anaemia, WCC and platelet initially high
blood film shows tear drop RBC
trephine biopsy shows fibrotic hypercellular marrow
JAK2 mutation present in 55%, CALR in 25%
high serum urate
what is the chance for each myeloproliferative disorder to develop into AML?
PV and ET = 5%
Primary myelofibrosis = 10-20%
Tx of primary myelofibrosis?
allogenic stem cell transplant (in young patients)
chemotherapy - hydroxycarbamide
supporitve e.g. blood transfusion + folic acid
what is the key diagnostic blast cell % to diagnose AML?
> 20%
what are myelodysplastic syndromes?
disorders characterised by increaseing bone marrow failure associated with dysplastic changes (prolfieration and apoptosis of haemopoeitic stem cells = hypercellular bone marrows and pancytopenia in peripherl blood)
clincial features of myelodysplastic disorders?
evolution slow and nromally picked up by chance
- anaemic symptoms (pallor, fatigue etc)
- infections
- bruising, bleeding
(spleen not enlarged)
heamatological features of myelodysplastic sydnromes?
- pancytopenia in peripheral blood
- hypercellular bone marrow w/ small number of dysplastic cells
what is chronic lymphocytic leukaemia (CLL)?
b cell lymphoma characterised by progressive accumulation of malignant clone of functionally incompetent B cells
clinical features of CLL?
mean age of diagnosis = 72 years
male>female
most common form of leukaemia seen in adults
80% diagnosed from routine blood tests
painless lymphadenopathy - most common sign
anaemia features
hepatosplenomegaly
repeated infections
what Ix are done to diagnose CLL?
fbc - lymphocytosis, low hb, anaemia in later stages, low neutrophils, low plt
blood film - smudge cells/smear cells
flow cytometry, karotype, immunohistochemistry
bone marrow cytology and histology - high % of small mature lymphocytes
genetics
lymph node biopsy
what is the difference between a bone marrow aspirate, trephine biopsy and bone marrow biopsy?
bone marrow aspirate - involved taking liquid sample from cell cytology
trephine biopsy - involves taking core sample of bone marrow (provides info on cells and structures)
bone marrow biopsy - taken from iliac crest using specialist needle
Mx for CLL?
if asymptomatic: observe and monitor
if symptomatic:
chemo - fludarabine + rituximab +/- cyclophosphomide
steroids - help autoimmune heamolysis
radio - helps lymphadenopathy and splenomegaly
stem cell transplant
supportive - transfusion, prophylaxis abx, human ig
what is hodgkins lymphoma?
malignant proliferation of lymphocytes characterised by presence of Reed Sternberg cells
main distinguishing feature ebtween hodgkins and non hodgkins?
histology presence of reed sternberg cells in hodgkins
clinical features of hodgkins?
lymphadenopathy - cervical (most common), axillary, inguinal
splenomegaly or hepatomegaly
nigth sweats, weight loss, fever (b symptoms)
alcohol induced pain in nodes
pruritus
what are the different subtypes of hodgkins lymphoma?
nodular sclerosing (70%)
mixed cellularity
lymphocyte rich (5%)
lymphocyte depleted (v rare)
risk factors for hodgkins lymphoma?
- EBV
- immunodeficiency: drugs, HIV, transplants
- autoimmune disease - sarcoid, RA
Ix need to diagnose hodgkins lymphoma?
fbc (pancytopenia), blood film, ESR, LFT, LDH (raised), urate (raised), calcium
CXR
PET/CT abdo/thorax/pelvis
lymph node excision biopsy (diagnostic!)
Mx of hodgkins lymphoma?
stages IA-IIA: radiotherapy (to localised large nodes) + short courses of chemo
stages IIA-IVB: longer course of chemo
chemo used:
- adriamycin
- bleomycin
- vinblastine
- dacarbazine
stem cell transplant used in relapse
how is hodgkins lymphoma staged?
ann arbor staging
I: confined to single region of nodes
II: two regions, same side of diaphragm
III: two or more regions across the diaphragm
IV: spread beyond nodes e.g. liver and bone marrow (spleen doesnt count)
each stage is either A or B:
A: no systemic symptoms other than pruritus
B: B symptoms listed above
complications of chemotherapy?
- myelosupression
- nausea
- alopecia
- infection
- non hodgkin lymphoma
- infertility
complications of radiotherapy?
risk of secondary malignancy - breast, lung, melanoma, sarcoma, thyroid
IHD, hypothyroid, lung fibrosis
What is non hodgkins lymphoma?
cancer of the lymphatic system affecting B cells or T cells
how can NHK lymphoma be classified?
B cells or T cells (low grade or high grade)
is hodgkins or non hodgkins lymphoma more popular?
non hodgkins
risk factors for non hodgkins lymphoma?
- age
- hx of EBV
- fam hx
- hx of chemo or radio
- HIV
- autoimmune disease - SLE, sjogrens, coeliac disease
clinical features of non hodgkins lymphoma?
painless lymphadenopathy - non tender, rubbery and asymmetrical over 2cm
gastric: dyspepsia, dysphagia, weight loss, abdo pain
small bowel: diarrhoea, vomit, abdo pain, weight loss
skin: mucosis fungoides
oropharynx: waldeyers ring lymphoma causes sore throat and obstructed breathing
bone, CNS and lung are other potential extra nodal sites
general features: fever, night sweats, weigth loss, pancytopenia
Ix for non hodgkins lymphoma?
fbc
u+e
lft
esr
bone profile
LDH
uric acid
HIV, hep B, hep C
imaging: cxr, CT neck, chest, abdo, pelvis
pet CT
MRI pelvis
testicular USS - identify testicular lymphoma
bone scan
biopsy - excision biopsy of affected lymph nodes or tissue
needle core biopsy (if unfit for excision biopsy)
additional: bone marrow aspirate an biopsy, LP (if suspected CNS), fluorescence in situ hybridisation
staging used in non hodgkins lymphoma?
ann arbor
Mx of non hodgkins lymphoma?
low grade: symptomless then none, radiotherapy in localised, chlorambucil in diffuse
retaining remission: rituxumab or interferon gamma
high grade: R-CHOP regime !!!
Rituximab
Cyclophosphamide
Hydroxydaunorubicin
vincristine (Oncovin)
Prednisolone
what is myeloma?
myeloma is a cancer of the plasma cells (type of B lymphocyte that produce antibodies)
what is the peak incidence of myeloma?
50-70s
more common in males
2nd most common haem malignancy
clinical features of myeloma?
CRABBI
c: calcium (hypercalcaemia symptoms: stones, groans, bones, psych moans)
r: renal failure
a: anaemia (syncope, pallor, fatigue)
b: bone lesions (pain/tender bones)
b: bleeding (thrombocytopenia)
i: infection
what Ix are done to diagnose myeloma?
plasma viscosity/ESR, serum calcium, FBC offered to anyone >60yo with unexplained bone pain or fracture
if any of those are skewed then order:
urgent serum electrophoresis, serum-free light chain assay, and Bence-Jones protein urine assessment
what is the criteria to diagnose myeloma?
symptomatic myeloma is defined by:
> 10% clonal bone marrow plasma cells in biopsy
+ one of:
monoclonal protein within serum or in urine (electrophoresis)
evidence of end organ damage (e.g. hypercalcaemia, renal insuffiency anaemia)
PET scan: lytic bone lesions or fractures
what supportive Mx is used in myeloma?
- analgesia (avoid NSAIDs)
- bisphosphonates due to fracture risk (give in hypercalcaemia)
- orthopaedic procedures
- transfusions and EPO (for anaemia)
- hydration and possible dialysis for renal
- abx - to prevent infections
- DOAC - VTE prophylaxis
- radiotherapy - improve bone pain
Mx for symptomatic myeloma?
induction therapy in those suitable for autologous stem cell transplantation (chemo):
bortezomib and dexamethasone
induction therapy in those unsuitable (chemo):
thalidomide + alkylating agent + dexamethasone
induction = 12 to 18 months
how is relapse of myeloma treated?
bortezomib monotherapy 1st line
some may be able to repeat autologous stem cell transplant, but case/case basis
what is MGUS?
monoclonal gammopathy of undetermined significance
excess of single type of antibody or antibody component without any other features of myeloma
often incidental finding in otherwise health
common causes of lymphadenopathy?
infections
autoimmune disease
malignanices
drug reaction s
functions of the spleen?
- removal of old or damaged WBC, RBC and platelets
- prevention of infection
causes of hyposplenism?
sickle cell anaemia
alcoholic liver disease
essential thrombocythaemia
hodgkins + non hodgkins + CLL
bone marrow transplantation
IBD + coeliac
operative splenectomy (in trauma)
Mx of hyposplenism?
- immunisations
- abx prophylaxis (phenoxymethylpenicillin or macrolideS)
causes of splenomegaly?
infections (e.g. malaria, EBV, endocarditis)
portal HTN from liver cirrhosis
leukamias and lymphomas
haemolytic anaemias
sickle cell disease
SLE, RA
what is leukostasis?
excess WBC in the blood leading to microvascular obstruction and ischameia
what are the tests done on bone marrow aspirate to help diagnose?
- morphology of the aspirate (looking at cells)
- flow cytometry/immunophenotyping (looks at markers on cells e.g. to see if myeloid or lymphoid)
- cytogenetics (e.g. BCR-ABL test to look for ph chromosome)
- molecular analysis
name some causes of pancytopenia?
meds!!! e.g. methotrexate
myelodysplastic syndromes
AML, ALL
severe folate and B12 deficiency
what is a normal amount of blast cells in a bone marrow aspirate?
<5% blast cells
