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Y4 medicine > Cancer - Haematology > Flashcards

Cancer - Haematology Flashcards

1
Q

name the myeloid malignancies

A

acute myeloid leukaemia
chronic myeloproliferative neoplasms

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2
Q

name the lymphoid malignancies

A

acute lymphoblastic leukaemia
chronic lymphocytic leukaemia
lymphoma

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3
Q

symptoms of bone marrow failure

A

anaemia
thrombocytopaenia
neutropenia

(pancytopenia)

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4
Q

symptoms of disease involvement in heam malignancies

A

lumps
organomegaly
any site

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5
Q

systemic symptoms in heam amlignancy

A

unintentional weight loss
drenching night sweats
fevers
pruritis

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6
Q

what blood tests do you do when ivnestigating a heam malignancy?

A

FBC, U+Es, LFT, CRP, Ca2+
heamtinics, retics, blood film
LDH, urate, B2M, PV+
If +/- SFLC
PB immunophenotyping

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7
Q

what imaging would be done when investigating haem malignancy?

A

CT scan
PET scan (lymphoma/myeloma)
MRI spine/pelvis (myeloma)

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8
Q

invasive investigations to be done when investigatings haem malignancy?

A

tissue biopsy
BM aspirate and trephine

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9
Q

name the chronic myeloproliferative neoplasms?

A

red cells: polycythaemia

platelets: thrombocythaemia

white: CML (leukaemia)

myeloid cells: primary myelofibrosis

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10
Q

what is acute lymphoblastic leukaemia?

A

malignancy of the lymphoid cells affecting B or T cells with uncontrolled proliferation of immature blast cells

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11
Q

clincial features in a pt with ALL?

A

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)
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12
Q

Ix to do in a pt with suspected ALL?

A

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

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13
Q

supportive Mx of ALL + AML ?

A
  • blood/platelet transfusion
  • IV fluids
  • allopurinol: prevent tumour lysis syndrome
  • prophylactic abx (high risk of neutropenic sepsis)
  • insert port system/hickman line
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14
Q

Tx of ALL?

A

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

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15
Q

what is remission defined as in ALL?

A

no evidence of leukaemia in blood, normal recoverign blood count and <5% blasts in normal regeneratign marrow

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16
Q

classic presentation of ALL?

A
  • 80% of childhood leukamia
  • peak incidence around 2-5yo, 75% of cases below age 6
  • boys>girls
  • associated with downs
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17
Q

poor prognosis factors for ALL?

A
  • less than 2 or older than 10
  • WBC >20
  • T or B cell surface markers
  • non caucasion
  • male
  • philadelphia chromosome
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18
Q

what are blast cells?

A

early heamopoietic cells (immature) that accumulate in the bone marrow in leukaemia

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19
Q

what age is AML most common in?

A

median onset at 65 years (most common form of acute leukaemia in adults)

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20
Q

what are the clinical features of AML?

A
  • bone marrow failure
  • neutropenia: infections
  • bleeding, bruising, petechiae (from thrombocytopenia + DIC)
  • anaemia: fatigue, pallor, syncope
  • gum hypertrophy + infiltration
  • skin involvement + CNS disease
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21
Q

Tx in AML?

A

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

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22
Q

what are teh 3 phases of CML and how do they present?

A

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

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23
Q

peak age of CML?

A

age 50-60
more common in males

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24
Q

characteristic feature of CML in karotyping?

A

translocation between chromosomes 9 and 22: presence of philadelphia chromosome (present in >80% CML cases)

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25
Q

clinical features of CML?

A

(chronic and insidious)

  • weight loss, anorexia, night sweats
  • splenomegaly
  • anaemia: pallor, dyspnoea, tachy, tiredness
  • thrombocytopaenia: bleeding, bruising
  • gout features due to hyperuricaemia
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26
Q

Ix to diagnose CML?

A
  • fbc: wcc massively increased
  • raised neutrophils, monocytes, basophils, eosinophils
  • low hb
  • u+es: high urate levels
  • raised b12
  • bone marro biopsy - hypercellular
  • cytogenic analysis
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27
Q

Mx of CML?

A

imatinib (tyrosine kinase inhibitor) = 1st line

other: hydroxyurea, interferon-alpha, allogenic bone marrow transplant

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28
Q

what are the genetic mutations that lead to myeloproliferative disorders

A

PV -> JAK2
essential thrombocythaemia -> JAK2, CALR, MPL
primary myelofibrosis -> JAK2, CALR, MPL

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29
Q

clinical features of polycythaemia vera?

A

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
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30
Q

what blood findings wld you see in polycythaemia vera?

A

raised heamoglobin
marrow biopsy
genetic testing - looks for JAK2 mutation

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31
Q

Tx for polycythaemia vera?

A
  1. venesection
  2. aspirin
  3. chemotherapy
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32
Q

what is essential thrombocythaemia?

A

raised platelet count due to megakaryocyte proliferation

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33
Q

clinical features of essential thrombycythaemia

A

thrombosis and haemorrhage
however most picked up on routine blood tests

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34
Q

how is a diagnosis of essential thrombocythaemia made?

A
  1. platelet count >450
  2. presence of acquired mutation (JAK2, CALR)
  3. no other myeloid malignancy, PV, primary myelofibrosis, chronic myeloid leukaemia, or myelodysplastic syndrome
  4. no reactive cause + normal iron stores
  5. bone marrow trephine histology shows increased megakaryocytes

diagnosis: 1-3 or 1 + 3-5

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35
Q

treatment for essential thrombocythaemia?

A

aspirin in low risk (<40yo)
hydroxycarbamide in high risk (>60yo, thrombosis risk high, platelet count >1500)

36
Q

what is primary myelofibrosis?

A

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

37
Q

clinical features of primary myelofibrosis?

A

anaemia symptoms
splenomegaly with abdo discomfort, pain w/ portal HTN
weight loss, anorexia, fever, night sweats
bleeding
bone pain
gout

38
Q

diagnosis of primary myelofibrosis?

A

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

39
Q

what is the chance for each myeloproliferative disorder to develop into AML?

A

PV and ET = 5%
Primary myelofibrosis = 10-20%

40
Q

Tx of primary myelofibrosis?

A

allogenic stem cell transplant (in young patients)
chemotherapy - hydroxycarbamide
supporitve e.g. blood transfusion + folic acid

41
Q

what is the key diagnostic blast cell % to diagnose AML?

A

> 20%

42
Q

what are myelodysplastic syndromes?

A

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)

43
Q

clincial features of myelodysplastic disorders?

A

evolution slow and nromally picked up by chance

  • anaemic symptoms (pallor, fatigue etc)
  • infections
  • bruising, bleeding

(spleen not enlarged)

44
Q

heamatological features of myelodysplastic sydnromes?

A
  • pancytopenia in peripheral blood
  • hypercellular bone marrow w/ small number of dysplastic cells
45
Q

what is chronic lymphocytic leukaemia (CLL)?

A

b cell lymphoma characterised by progressive accumulation of malignant clone of functionally incompetent B cells

46
Q

clinical features of CLL?

A

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

47
Q

what Ix are done to diagnose CLL?

A

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

48
Q

what is the difference between a bone marrow aspirate, trephine biopsy and bone marrow biopsy?

A

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

49
Q

Mx for CLL?

A

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

50
Q

what is hodgkins lymphoma?

A

malignant proliferation of lymphocytes characterised by presence of Reed Sternberg cells

51
Q

main distinguishing feature ebtween hodgkins and non hodgkins?

A

histology presence of reed sternberg cells in hodgkins

52
Q

clinical features of hodgkins?

A

lymphadenopathy - cervical (most common), axillary, inguinal
splenomegaly or hepatomegaly
nigth sweats, weight loss, fever (b symptoms)
alcohol induced pain in nodes
pruritus

53
Q

what are the different subtypes of hodgkins lymphoma?

A

nodular sclerosing (70%)
mixed cellularity
lymphocyte rich (5%)
lymphocyte depleted (v rare)

54
Q

risk factors for hodgkins lymphoma?

A
  • EBV
  • immunodeficiency: drugs, HIV, transplants
  • autoimmune disease - sarcoid, RA
55
Q

Ix need to diagnose hodgkins lymphoma?

A

fbc (pancytopenia), blood film, ESR, LFT, LDH (raised), urate (raised), calcium
CXR
PET/CT abdo/thorax/pelvis
lymph node excision biopsy (diagnostic!)

56
Q

Mx of hodgkins lymphoma?

A

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

57
Q

how is hodgkins lymphoma staged?

A

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

58
Q

complications of chemotherapy?

A
  • myelosupression
  • nausea
  • alopecia
  • infection
  • non hodgkin lymphoma
  • infertility
59
Q

complications of radiotherapy?

A

risk of secondary malignancy - breast, lung, melanoma, sarcoma, thyroid
IHD, hypothyroid, lung fibrosis

60
Q

What is non hodgkins lymphoma?

A

cancer of the lymphatic system affecting B cells or T cells

61
Q

how can NHK lymphoma be classified?

A

B cells or T cells (low grade or high grade)

62
Q

is hodgkins or non hodgkins lymphoma more popular?

A

non hodgkins

63
Q

risk factors for non hodgkins lymphoma?

A
  • age
  • hx of EBV
  • fam hx
  • hx of chemo or radio
  • HIV
  • autoimmune disease - SLE, sjogrens, coeliac disease
64
Q

clinical features of non hodgkins lymphoma?

A

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

65
Q

Ix for non hodgkins lymphoma?

A

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

66
Q

staging used in non hodgkins lymphoma?

A

ann arbor

67
Q

Mx of non hodgkins lymphoma?

A

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

68
Q

what is myeloma?

A

myeloma is a cancer of the plasma cells (type of B lymphocyte that produce antibodies)

69
Q

what is the peak incidence of myeloma?

A

50-70s
more common in males
2nd most common haem malignancy

70
Q

clinical features of myeloma?

A

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

71
Q

what Ix are done to diagnose myeloma?

A

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

72
Q

what is the criteria to diagnose myeloma?

A

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

73
Q

what supportive Mx is used in myeloma?

A
  • 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
74
Q

Mx for symptomatic myeloma?

A

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

75
Q

how is relapse of myeloma treated?

A

bortezomib monotherapy 1st line
some may be able to repeat autologous stem cell transplant, but case/case basis

76
Q

what is MGUS?

A

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

77
Q

common causes of lymphadenopathy?

A

infections
autoimmune disease
malignanices
drug reaction s

78
Q

functions of the spleen?

A
  • removal of old or damaged WBC, RBC and platelets
  • prevention of infection
79
Q

causes of hyposplenism?

A

sickle cell anaemia
alcoholic liver disease
essential thrombocythaemia
hodgkins + non hodgkins + CLL
bone marrow transplantation
IBD + coeliac
operative splenectomy (in trauma)

80
Q

Mx of hyposplenism?

A
  1. immunisations
  2. abx prophylaxis (phenoxymethylpenicillin or macrolideS)
81
Q

causes of splenomegaly?

A

infections (e.g. malaria, EBV, endocarditis)
portal HTN from liver cirrhosis
leukamias and lymphomas
haemolytic anaemias
sickle cell disease
SLE, RA

82
Q

what is leukostasis?

A

excess WBC in the blood leading to microvascular obstruction and ischameia

83
Q

what are the tests done on bone marrow aspirate to help diagnose?

A
  • 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
84
Q

name some causes of pancytopenia?

A

meds!!! e.g. methotrexate
myelodysplastic syndromes
AML, ALL
severe folate and B12 deficiency

85
Q

what is a normal amount of blast cells in a bone marrow aspirate?

A

<5% blast cells

Y4 medicine (17 decks)

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