Haematological malignancy Flashcards

1
Q

What is the pathophysiology of ALL?

A

Proliferation of malignant precursor lymphoid cells in the bone marrow. Either B (most common) or T cells.
The proliferating malignant cells replace normal lines = normal suppressed = anaemia, thrombocytopenia and neutropenia.
Most common in children, 2-4 years.

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2
Q

What is the Philadelphia chromosome?

A

t(9;22) - associated w a poor prognosis
BCR gene and ABL gene swap (BCR-ABL) = increases tyrosine kinase = tells the cells to keep on proliferating = cancer, particularly in CML

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3
Q

What are the different groups of CF associated w ALL?

A

Marrow failure
Tissue infiltration
Leucostasis

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4
Q

What are the CF of marrow failure?

A

Anaemia - fatigue, SOB, angina, palor
Neutropenia - recurrent infections, sore throat, fever
Thombocytopenia - petechiae, nose bleeds, bruising

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5
Q

What are the CF of tissue infiltration?

A

Lymphadenopathy and hepatosplenomegaly - common at diagnosis
Bone pain
Mediastinal mass - could cause SVCO
Testicular enlargement

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6
Q

What is leucostasis?

A

Increased WCC in blood = thicker blood/impaired flow through small vessels: alt mental state, headache, breathlessness, visual changes
Also called meningeal syndrome - headache, N+V, blurred vision and diplopia - fundoscopy = papilloedema

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7
Q

What are the blood ix into ALL?

A

FBC - anaemia, thrombocytopenia, leucocytosis and neutropenia
U+E and LFTs - hypercalcaemia from paraneoplastic sydnrome, also baseline to check func before begin treatment
Coag screen and D dimer - assess for DIC
Uric acid and LDH - non specific markers of tumour burden
BBV screen ?
Blood film - blast cells

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8
Q

What is the imaging into ALL?

A

CXR - may have mediastinal mass
CT chest, AP - lymphadenopathy and organ involve, lytic lesions, enlarged thymus in T ALL
CT/MRI head - if pt sx indicate neuro involve

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9
Q

What is the diagnostic test in ALL?

A

Bone marrow aspiration and biopsy:
- Staining
- Review cell morphology
- Immumophenotyping
- Cytogenetics
- Flow cytometry

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10
Q

What are some additional ix into ALL?

A
  • Blood film - blast cells
  • Pleural tap
  • LP - if concerned about CNS involve (but can promote spread of tumour cells into CNS)
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11
Q

What factors are associated w poorer prognosis in ALL?

A

(in adult pt):
- Increasing age
- Performance status >1
- High WCC - >30 B cell and >100 T cell
- Philadelphia chromosome
- CNS involvement

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12
Q

What is the classification of ALL?

A

Morphological
Immunological - surface markers
Cytogenic - chromosomal analysis, used for prognostic assessment

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13
Q

What is the supportive management of ALL and AML?

A

Blood <80g/l/platelet <10/l transfusion or<20 if bleed/septic
IV fluids, electrolyte replacement + allopurinol - prevent tumour lysis syndrome
Port system or Hickman line inserted
Infection prevention - prophylactic abx, anti virals and anti fungals
Anti emetics - ondansetron and they possible addition of dex, treat before N happens
Fertility treatment eg. freeze sperm/eggs
Macmillan nurse

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14
Q

What is the definitive management of ALL?

A

Chemo:
- Complex multi drug chemo, have multiple rounds and may take years
- Induce remission - vincristine, preg, L-asparaginase, daunorubicin
- Possible stem cell transplant
- CNS prophylaxis - IT/IV mtx
- Maintenance - prolonged chemo agents for 2 years eg. vincristine, dex, mtx

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15
Q

What is the pathophysiological of AML?

A

Genetic changes in myeloid precursor cells = proliferating immature cells that don’t respond to normal control mechanisms.
Results in reduced normal haemopoiesis.

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16
Q

What are some RF of AML?

A
  • Myelodysplastic syndrome - blood disorders that affect haemopoiesis
  • Down’s syndrome and other congenital disorders
  • Radiation exposure
  • Prev chemo
  • Increasing age ~70 years
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17
Q

What are the CF of AML?

A

Marrow failure
Leucostasis
Tissue infiltration:
- Lymphadenopathy and hepatosplenomegaly
- Bone pain
- Gum hypertrophy
- Violaceous skin deposits
- Testicular enlargement

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18
Q

What are the blood ix into AML?

A

FBC - anaemia, thrombocytopenia, reduced reticulocyte, raised WCC
U+E - important when ruling out tumour lysis
Coag screen to rule out DIC
LDH - raised = high cell turnover
BBV screen
Blood film - Auer rods in myeloid blasts = pathognomonic

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19
Q

What are the other ix into AML?

A
  • BM aspirate and trephine biopsy - >20% blast count, then cytogenetics, cytometry, immunophenotyping
  • LP
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20
Q

What is the definitive treatment of AML?

A

Chemo - 5 cycles given in 1 week blocks = daunorubicin, cytarabine, given in blocks to allow blood count to recover in between, takes ~4-6 w
Marrow transplant - eradicate abnormal cells first then repopulate w donor marrow, give immunosuppression to prevent rejection, poor prognosis or relapse

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21
Q

What are the poor prognostic factors of AML?

A

> 60
20% blasts after 1st round of chemo
Poor performance status/comorbidities
Prev haematological disorders/dysplasia
Prev chemo/RT

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22
Q

What is chronic lymphocytic leukaemia?

A

Abnormal cloncal expansion of B cells that resemble mature lymphocytes = widespread lymphadenopathy and secondary immune def and cytopenias

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23
Q

What is the timeline of CLL?

A

Some pt are asymptomatic for many years
Others may get rapidly progressive disease that is symptomatic - progressive lymphadenopathy, hepatosplenomegaly

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24
Q

What are the CF of CLL?

A

Lymphadenopathy !!
Sx - weight loss, fever, anorexia, night sweats, lethargy
Signs - lymphadenopathy, hepatomegaly, splenomegaly
Features due to complications - autoimmune haemolytic anaemia (pale, SOB, fatigue), ITP (petechiae, bruise, bleed), recurrent infections

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25
Q

What are ix into CLL?

A

FBC - raised lymphocytes, low Hb then haemolysis, low neutrophils and low platelets = BM failure
Blood film - smudge cells, smear cells !!!!!! most important
Flow cytometry, immunohistochemistry, cytogenetics
LN biopsy

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26
Q

What are the different types of BM biopsy?

A

Marrow aspirate - liquid sample for cytology
Trephine biopsy - core sample
BM biopsy

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27
Q

What is the staging of CLL?

A

Binet:
Stage A <3 lymphoid sites - >10yr
Stage B >3 lymphoid sites >8yr
Stage C = anaemia and thrombocytopenia ~6.5yr
Rai staging:
Stage 0 - lymphocytosis
Stage I-II - lymphocytosis + lymphadenopathy + organomegaly
Stage III-IV - lymphocytosis + anaemia or thrombocytopenia + organomegaly + lymphadenopathy

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28
Q

What are some prognosis factors?

A
  • Lymphocyte doubling time, the faster the worse the prognosis
  • Genetic abnormalities = TP53, trisomy 21
  • B2M
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29
Q

What is the management of CLL?

A
  • Watch and wait for asymptomatic pt w/o poor prognostic factors
  • Pharmacotherapy
  • Allogenic stem cell transplant - chemo to destroy BM then replace w donor haemopoietic stem cells
  • Supportive care
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30
Q

What are indications for treatment of CLL?

A
  • BM failure
  • Massive, progressive or symptomatic splenomegaly/lymphadenopathy/lymphocytosis
  • Autoimmune complications not responsive to steroids eg. ITP
  • Disease related sx
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31
Q

What pharmacotherapy things can be used for CLL?

A

Chemo - chlorambucil, fludarabine, bendamustine
Small molecule inhib - ibrutinib (tyrosine kinase inhib), idelalisib, venetoclax
Monoclonal ab - rituximab
Steroids in vv frail pt

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32
Q

What is Richter transformation?

A

CLL to aggressive lymphoma, ~5-8 month survival

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33
Q

What genetic abnormality is found in CML?

A

Ph chromosome
BCR-ABL blood test for disease response, should be reducing

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34
Q

What is chronic myeloid leukaemia?

A

Clonal myeloproliferative neoplasm w abnormal expansion of cells of myeloid lineage, most commonly granulocyte

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35
Q

What are the phases of CML?

A

Chronic - ~5 years, asymptomatic or non specific sx
Accelerated - abnormal blast cells take up ~20% of BM, symptomatic
Blast - 30% of BM is blast cells, causes pancytopenia, often fatal

36
Q

What are the CF of CML?

A
  • Asymptomatic and picked up on routine bloods
  • Splenomegaly - early satiety, abdo pain !!!!! biggest one
  • Fatigue
  • Weight loss
  • Night sweats
  • Sx of anaemia, thrombocytopenia, leucostasis
  • Bone pain
  • Lymphadenopathy
37
Q

What are the blood ix into CML?

A

FBC - high WCC, anaemia, thrombocytosis
Blood film - immature and mature myeloid cells
LDH, urate and K = markers of cell turnover

38
Q

What are the other ix into CML?

A

BM aspirate +/- trephine = review % of blasts etc

39
Q

What is the management of CML?

A

Tyrosine kinase inhib !!
Intensive chemo for pt w blastic transformation
Allogenic stem cell transplant - chronic phase pt who have failed other options or adv disease, not used as much as lots of different TKI to try first

40
Q

What are some TKIs?

A

Imatinib - favourite ?
Dasatinib
Nilotinib

41
Q

What are the myeloid cells?

A

Megakaryocytes/thrombocytes
Erythrocytes
Eosinophil, basophil, neutrophil, monocyte

42
Q

What are the lymphoid cells?

A

Lymphocytes - B or T

43
Q

What is trephine biopsy?

A

bone marrow core biopsy

44
Q

What is remission defined as for AML?

A

<5% blasts w/o Auer rods

45
Q

Hodgkin lymphoma vs non Hodgkin lymphoma?

A

Hodgkin - Reed Sternberg cells
Non Hodgkin - no Reed Sternberg cells, lots of subtypes, most common type of lymphoma

46
Q

What are the CF of HL?

A

Gradual lymphadenopathy
B sx
Mediastinal mass - can be incidental or SOB, coug, SVCO
Pruritis
Hepatosplenomegaly
Malaise and fatigue

47
Q

What are the ix into HL and NHL?

A

Excision biopsy of affected LN - whole incision or core (not FNA!!)
Bloods - FBC, U+E, LFT, bone, LDH, uric acid, ESR, BBV
Imaging - CXR, CT neck thorax AP w contrast, MRI brain if suspect CNS, PET once you have confirmation of cancer type

48
Q

What staging system is used for HL and NHL?

A

Ann Arbor
1 - localised LN
2 - 2+ LN on same side of diaphragm
3 - 2+ LN on either side of diaphragm, inc splenomegaly?
4 - widespread disease, extra nodal involvement
a - no b sx
b - b sx

49
Q

What is the most common regimen for HL treatment?

A

ABVD
A - doxorubicin
Bleomycin
Vinblastine
Dacarbazine
Commonly use w RT as well

50
Q

What are the rules for blood transfusion in HL?

A

If have HL or have ever had HL need irradiated red cells and platelets for life - reduce risk of transfusion associated graft vs host disease ?

51
Q

What is the prognosis of HL?

A

75% + pt cured, prognosis ~90% 5 years

52
Q

What are the RF of HL?

A

HIV, EBV, RA, sarcoidosis, FH

53
Q

What are the CF of non Hodgkin lymphoma?

A

Lymphadenopathy !!
Fever
Night sweats
Weight loss
Pruritis
Hepatosplenomegaly
Can present w oncological emergency

54
Q

What is the common chemo regimen to treat NHL?

A

Only treat once a patient isn’t well or has high grade cancer, otherwise active surveillance
R-CHOP
Rituximab - attacks CD20 = B cell
Cyclophosphamide
Doxorubicin
Vincristine
Pred

55
Q

What is the most common type of NHL?

A

Diffuse large B cell lymphoma - rapidly enlarging mass commonly in neck, abdo or mediastinum, high grade
Follicular lymphoma - most common low grade, 20% transform to DLCL

56
Q

What are some other types of NHL?

A

B cell low grade - follicular and MALT lymphoma, associated w H.pylori
B cell high grade - Burkitt (children), DLBCL

57
Q

What are the RF of NHL?

A

HIV, EBC, H.pylori, Coeliac’s, Hep B or C, FH

58
Q

What is paraprotein?

A

If high = myeloma
Plasma cells make one of 5 types of ab = A G M D and E. In myeloma 1 type will be very high, most of the time its G.
The single type of Ab produced by all the cancerous plasma cells is a monoclonal paraprotein.

59
Q

What is multiple myeloma?

A

Malignant disorder of plasma cells, they are a type of B lymphocyte that produces Ab. Cancer in a specific type of plasma cell results in large quantities of a single type of ab produced.
Multiple = when myeloma affects multiple areas of the body

60
Q

What is MGUS?

A

Monoclonal gammopathy of undetermined significance = too much of a single type of ab w/o features of myeloma/cancer
May progress to myeloma but don’t know

61
Q

What is smouldering myeloma?

A

Progression of MGUS w higher levels of ab, is premalignant.
More likely to progress to myeloma than MGUS

62
Q

What are the CF of multiple myeloma?

A

Features related to infiltration of plasma cells and ab secretion:
- Bone disease eg. lytic lesions, clonal prolif in bone marrow
- Impaired renal func
- Anaemia - BM infilitration
- Hypercalcaemia - bone demineralisation
- Recurrent infection - suppression of normal plasma cell func
CRAB

63
Q

What does CRAB stand for?

A

Calcium levels high
Renal impairment
Anaemia
Bone disease

64
Q

What specific syndromes can multiple myeloma present with?

A

Hyperviscosity syndrome - high paraprotein levels eg. IgA or IgG = blurred vision, headaches, mucosal bleed, SOB = urgent plasma exchange needed
Spinal cord compression - 5% of pt get

65
Q

When should you suspect myeloma?

A

> 60 years with…
Unexplained bone pain and pathological fractures - feel sternum and spine esp for tenderness
Fatigue
Hypercalcaemia sx
Weight loss
Sx of MSCC
Sx of hyperviscosity
Recurrent infections

66
Q

What are the tests for myeloma?

A

Bloods - FBC, Ca, ESR, plasma viscosity
BLIP!
Bence Jones protein via urine electrophoresis - however don’t really care anymore
Light chain assay (serum) - Kappa Lambda
Immunoglobulins
Protein electrophoresis - don’t really care
Bone marrow biopsy
Whole body 1. MRI 2. CT 3. skeletal survey BUT normally do PET scan

67
Q

What are the XR signs of myeloma?

A

Punched out lesions
Lytic lesions
Raindrop skull - many lytic lesions

68
Q

MGUS vs smouldering vs myeloma

A

MGUS - paraprotein low, BM plasma cells <10%, no organ damage
Smouldering - paraprotein normal, BM plasma cell >10%, no organ damage
Myeloma - paraprotein ++, BM plasma cell >10%, organ damage

69
Q

What is the management of myeloma?

A

Control the disease- relapses and remitted, can’t really cure?
1. Chemo - bortezomib, thalidomide, dex
2. Stem cell transplant - from self, not allogenic
VTE prophylaxis

70
Q

How do you manage myeloma bone disease?

A

Bisphosphonates
RT
Orthopaedic surgery to stabilise fractures

71
Q

What is myelodysplastic syndrome?

A

Myeloid BM cells don’t mature properly and so don’t produce normal blood cells.
More common in >60 and pt who have prev had chemo or RT.
Increased risk of transforming to AML

72
Q

What is the presentation of myelodysplastic syndrome?

A

Asymptomatic and incidentally diagnosed on FBC or have sx:
- Anaemia sx
- Neutropenia sx
- Thrombocytopenia sx

73
Q

What is the management of myelodysplastic syndromes?

A

Watch and wait
Blood transfusions when severely anaemic
Chemo ?
Stem cell transplant ?

74
Q

What are the types of myeloproliferative neoplasms/disorders?

A
  1. Primary myelofibrosis
  2. Polycythaemia vera
  3. Essential thrombocythaemia
75
Q

What is primary myelofibrosis?

A

Proliferation of haematopoietic stem cells
Causes fibrosis of BM
Teardrop RBC on film poikilocytosis

76
Q

What is polycythaemia vera?

A

Proliferation of erythroid cell line
Raised Hb

77
Q

What is essential thrombocythaemia?

A

Proliferation of megakaryocytic cell line
>600 plt

78
Q

What is the worry associated w myeloproliferative disorders and what mutations are associated w them?

A

Can transform to AML
Mutations - JAK2, (MPL, CALR ??)

79
Q

What is the presentation of myeloproliferative disorders?

A

Asymptomatic
Systemic sx - fatigue, weight loss, night sweats, fever
Splenomegaly
Anaemia (except polycythaemia) and thrombocytopenia
Thrombosis - rairsed WBC and platelets
Portal HTN

80
Q

What are the signs o/e that will make you suspect polycythaemia vera?

A
  1. Conjunctival plethroa
  2. Ruddy complexion
  3. Splenomegaly
81
Q

What is the management of primary myelofibrosis?

A

Allogenic stem cell transplant - can be curative
Chemo - not curative but slow progression and improve sx
Supportive management

82
Q

What is the management of polycythaemia vera?

A

1st line = therapeutic venesection
Aspirin used to prevent VTE
Chemo

83
Q

What is the management of essential thrombocythaemia?

A

Aspirin to prevent VTE
Chemo

84
Q

What tests do you do on BM biopsy?

A

Flow cytometry and immunophenotyping - tell you what type of cell the blast is eg. B or T cell, neutrophil or lymphocyte
Morphology - liquid slide = like a film, can see the cells
Cytogenetics eg. Ph chromosome

85
Q

How can you differentiate all the leukaemias?

A

Acute - just blast cells
Chronic - have blast cells and other stages of immature cells

86
Q

What are poor prognostic factors in lymphoma?

A

HL - raised ESR
NHL - raised LDH