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Year 3 - Haematology (DP) > Haematopoiesis, White Cells + Their Disorders > Flashcards

Haematopoiesis, White Cells + Their Disorders Flashcards

1
Q

How can mature blood cells be identified?

A

Morphology
Cell surface antigens
Enzyme expression

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2
Q

How can progenitors and stem cells be identified?

A

Cell surface antigens
Cell culture assays
Animal models

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3
Q

What cell surface antigen is present on RBCs?

A

Glycophorin A

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4
Q

What enzyme is expressed in Neutrophils?

A

Myeloperoxidase

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5
Q

What happens in malignant haematopoiesis?

A

One or more of the following:

  • Increased proliferation
  • Lack of differentiation
  • Lack of maturation
  • Lack of apoptosis
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6
Q

What are ‘driver mutations’?

A

Confer growth advantage

Positively selected during cell evolution

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7
Q

What are ‘passenger mutations’?

A

No growth advantage

Present in ancestor when it acquired its driver

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8
Q

What is a clone?

A

A population of cells derived from a single parent cell

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9
Q

What is the clonality of normal haematopoiesis?

A

Polyclonal

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10
Q

What is the clonality of malignant haematopoiesis?

A

Monoclonal

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11
Q

What are the features of a ‘high-grade’ lymphoma?

A 
Aggressive histology (large primitive cells)
Aggressive clinical features
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12
Q

What is a myeloma?

A

Plasma cell malignancy in marrow

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13
Q

What is an acute leukaemia defined as?

A

Rapidly progressive clonal malignancy of marrow/blood with maturation defect(s)
Excess of ‘blasts’ (>=20%) in either:
- Peripheral blood
- Bone marrow
Decrease/Loss of normal haematopoietic reserve

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14
Q

What are the classifications of acute lymphoblastic leukaemia?

A

Precursor B cell
Precursor T cell
B cell:
- Burkitt’s lymphoma/leukaemia

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15
Q

Why causes acute lymphoblastic leukaemia to present?

A 
Marrow failure:
- Anaemia
- Infections
- Bleeding
Bone pain
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16
Q

What are the leukaemic effects in ALL?

A

High WCC
Involvement of extramedullary areas
Venous obstruction (due to LNs)

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17
Q

Who is acute myelogenous leukaemia more common in?

A

Elderly (>60)

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18
Q

What chromosomal translocation is seen in acute promyelocytic leukaemia?

A

t(15;17)

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19
Q

How can acute promyelocytic leukaemia present?

A

DIC

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20
Q

How does AML present?

A 
Similar to ALL (marrow failure)
Gum infiltration (in some subgroups)
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21
Q

What does a blood count and film show in acute leukaemia?

A

Reduction in normal cells
Presence of abnormal cells
Cells with high nuclear:cytoplasmic ratio

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22
Q

What are Auer rods and what are they seen in?

A

Red-staining ‘needles’ in cytoplasm of myeloblasts

Seen in AML

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23
Q

How can a definitive diagnosis of acute leukaemia be made?

A

Bone marrow for immunophenotyping:

- Expression of lineage-associated proteins

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24
Q

What is a trephine and when is it useful?

A

Piece of bone

When bone marrow aspirate is sub-optimal

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25
Q

How long can chemotherapy in ALL last?

A

2-3 years

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26
Q

What are the phases of chemotherapy in ALL?

A
  1. Induction
  2. Consolidation
  3. Maintenance
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27
Q

What is a typical cycle of chemotherapy in AML?

A

5-10 days of chemo following by 2-4 weeks of recovery

Total 2-4 cycles

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28
Q

What are the problems related to marrow suppression?

A

Anaemia
Neutropaenia
Thrombocytopaenia

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29
Q

What bacteria tend to cause infections in marrow suppression due to neutropaenia?

A

Gram negative bacteria:

- Fulminant, life-threatening sepsis

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30
Q

What does thrombocytopaenia result in?

A

Bleeding:

  • Purpura
  • Petechiae (platelets <20x10^9)
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31
Q

What is tumour lysis syndrome?

A

Metabolic abnormality that results when a lot of tumour cells are killed off at once (normally during the first cycle of treatment), releasing their contents into the blood stream

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32
Q

How does tumour lysis syndrome present?

A

Symptoms/signs related to:

  • Hyperkalaemia
  • Hyperphosphataemia
  • Hypocalcaemia
  • Hyperuricaemia
  • High blood urea nitrogen
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33
Q

When should a fungal infection (during leukaemia treatment) be suspected?

A

Prolonged neutopaenia

Persisting fever unresponsive to ABx

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34
Q

When is protozoal (eg. PJP) infection more relevant?

A

ALL therapy

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35
Q

What are the long term complications of leukaemia therapy?

A

Loss of fertility

Cardiomyopathy (with anthracyclines)

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36
Q

What is the cure rate in childhood ALL?

A

> 85-90%

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37
Q

When can an allogenic stem cell transplant be used in leukaemia?

A

After initial therapy

At relapse

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38
Q

What is blinatumomab?

A

Bi-specific T cell enhancer

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39
Q

What are the differentials for night sweats?

A

Lymphoma
Infection
Menopause

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40
Q

What are the differentials for weight loss?

A

Lymphoma
Other malignancy
Infections

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41
Q

What are the symptoms of lymphoma?

A 
A 'lump'
General symptoms
Itch without a rash
Alcohol-induced pain
Fatigue
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42
Q

How does a ‘lump’ feel in lymphoma?

A 
Non-tender
Rubbery-Soft
Smooth
No skin inflammation
Not tethered
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43
Q

How useful is a CT in lymphoma?

A

Not useful

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44
Q

What CD number is seen in follicular NHL?

A

CD20+ cells

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45
Q

What CD number is seen in Hodgkin’s Lymphoma?

A

CD30+ Reed Sternberg Cells

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46
Q

In what patients is immunophenotyping useful?

A

Leukaemia
Lymphomas involving marrow:
- eg. Burkitt’s Lymphoma

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47
Q

What genetic change is seen in follicular NHL?

A

t(14;18)

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48
Q

What genetic change is seen in mantle cell NHL?

A

t(11;14)

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49
Q

What drug does activated B cell type NHL respond well to?

A

Ibrutinib

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50
Q

What is the most common group of lymphomas?

A

B-cell NHL

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51
Q 
What do the following indicate:
- Short stature
- Skin pigment abnormalities (inc. cafe au lait)
- Radial ray abnormalities
- Hypogenitalia
- Endocrinopathies
How is it inherited?
A

Fanconi’s anaemia

Autosomal recessive

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52
Q

How do inherited marrow failure syndromes arise?

A

Unable to correct inter-strand crosslinks resulting in DNA damage

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53
Q

What FBC changes are seen in inherited marrow failure syndromes?

A

Macrocytosis
Followed by:
- Thrombocytopaenia
- Then neutropaenia

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54
Q

What is the median age of onset of haematological abnormalities in inherited marrow failure syndromes?

A

7 years

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55
Q

What is the pathophysiology behind aplastic anaemia?

A 
Autoreactive T cells produce IFN-gamma and TNF-alpha against:
- LT-HSCs
- MPPs
- CMPs
Results in reduced production of:
- RBCs
- Platelets
- Granulocytes
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56
Q

What are the features of myelodysplastic syndrome?

A

Dysplasia
Hypercellular marrow
Increased apoptosis of progenitor and mature cells

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57
Q

What can myelodysplastic syndrome evolve into?

A

AML

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58
Q

What drugs can induce secondary bone marrow failure (aplasia)?

A

Chemotherapy
Chloramphenicol
Alcohol

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59
Q

What can cause hypersplenism?

A 
Splenic congestion:
- Portal hypertension
- CCF
Systemic diseases:
- RA (Felty's)
Haematological diseases:
- Splenic lymphoma
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60
Q

Apart from drugs, what other causes are there of secondary bone marrow failure?

A

B12/Folate deficiency
Infiltration
Miscellaneous

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61
Q

What is the cellularity of bone marrow in aplastic anaemia?

A

Hypocellular

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62
Q

What are some causes of hypercellular bone marrow in regards to pancytopaenia?

A

MDS
B12/Folate deficiency (eg. Megaloblastic anaemia)
Hypersplenism
(Malignant infiltration - Only gives a hypercellular appearance)

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63
Q

What are the possible variants of the heavy chains in immunoglobulins?

A 
mew
alpha
delta
gamma
epsilon
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64
Q

What are the possible variants of the light chains in immunoglobulins?

A

kappa

lambda

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65
Q

What is the part at the end of both the heavy chains and light chains in immunoglobulins?

A

Variable region

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66
Q

What part of the immunoglobulin does an antigen bind to?

A

The antigen binding site in the Fab region of the Ab

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67
Q

What part of the immunoglobulin forms the tail and binds to cell receptors?

A

Fc region

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68
Q

What immunoglobulins are typically monomers?

A

IgD
IgE
IgG

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69
Q

What immunoglobulin is a dimer?

A

IgA

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70
Q

What immunoglobulin is a pentamer?

A

IgM

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71
Q

Where is the Ig variable element generated from?

A

V-D-J region recombination early in development

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72
Q

What cells are removed during B-cell development?

A

Self-reactive

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73
Q

When happens to B cells in the periphery?

A

Follicle germinal centre of LN:

  • Identify Ag and improve fit or
  • Be deleted
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74
Q

What happens to a B cell after it is processed in the LN?

A

Return to marrow as a plasma cell
OR
Circulate as a memory cell

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75
Q

How does a plasma cell nucleus appear? Why?

A

Eccentric ‘clock-face’ nucleus on H+E stain:

- Open chromatin synthesising mRNA

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76
Q

How does a plasma cell appear?

A

Plentiful blue cytoplasm (laden with protein)

Pale perinuclear area (golgi)

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77
Q

What is a paraprotein?

A

Abnormal, monoclonal IG fragments or IG light chains

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78
Q

What is a paraprotein a marker of?

A

Underlying clonal B-cell disorder

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79
Q

From anode (+) to cathode (-), how do the following separated serum proteins appear?

  • Beta
  • Alpha-1
  • Alpha-2
  • Albumin
  • Gamma
A 
Albumin
Alpha-1
Alpha-2
Beta
Gamma
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80
Q

What is the main component of the Alpha-1 band/zone in serum electrophoresis?

A

Alpha-1 antitrypsin

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81
Q

What are the main components of the Alpha-2 band/zone in serum electrophoresis?

A

Alpha-2 macroglobulin
Caeruloplasmin
Haptoglobin

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82
Q

What are the main components of the Beta band/zone in serum electrophoresis?

A

Transferrin
Low density lipoprotein
C3

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83
Q

What are the main components of the Gamma band/zone in serum electrophoresis?

A

Immunoglobulins

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84
Q

What do the groupings of serum electrophoresis indicate?

A

Their mobility (not their functioning)

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85
Q

What is the purpose of serum immunofixation?

A

To classify the abnormal protein band

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86
Q

What is Bence-Jones protein?

A

Unusual protein precipitate found on warming urine which re-dissolves when heated

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87
Q

What were Bence-Jones proteins later identified as?

A

Ig light chains

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88
Q

How are Bence-Jones proteins detected?

A

Urine electrophoresis

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89
Q

What happens when immunoglobulins are made by plasma cells?

A

More light chains made than heavy chains:

- Free light chains secreted into plasma

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90
Q

How many free light chains are secreted into the plasma per day?

A

0.5g/day

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91
Q

What free light chains are monomeric?

A

kappa

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92
Q

What free light chains are dimeric?

A

lambda

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93
Q

What can cause an increased amount of free light chains?

A

Polyclonal increase in plasma cells (infection)

Monoclonal increase in plasma cells (myeloma)

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94
Q

What direct tumour cell effects can myeloma cause?

A 
Bone lesions
Increased calcium
Bone pain
Replace normal bone marrow:
- Marrow failure
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95
Q

What are the paraprotein mediated effects in myeloma?

A

Renal failure
Immune suppression
Hyperviscosity
Amyloid

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96
Q

What is the most common paraprotein produced in myeloma?

A

IgG

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97
Q

What is the least common paraprotein produced in myeloma?

A

IgE

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98
Q

When myeloma cells activate the RANKL receptors on bone marrow stromal cells what happens?

A

IL-6 is produced

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99
Q

When IL-6 is produced, what is produced and what cells are affected?

A

IL-6 levels are increased substantially
TGF-beta levels are increased
Osteoblasts are suppressed
Osteoclasts are activated

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100
Q

What happens when osteoclasts are activated in myeloma?

A

Hyeprcalcaemia

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101
Q

What bone lesions are seen in myeloma?

A

Lytic:

- Plain radiographs may show ‘punched-out’ lesions

102
Q

What can bone lesions in myeloma result in?

A

Wedge compression spinal fractures

103
Q

How much paraprotein can the PCT in the kidney reabsorb and catabolise per day?

A

10-30g

104
Q

What happens, in regard to paraproteins, if the PCT is damaged or overwhelmed?

A

Paraproteins enter the Loop of Henle

105
Q

What is produced when paraproteins enter the ascending limb of the Loop of Henle?

A

Tamm-Horsfall protein:

  • Combines with paraproteins
  • Insoluble casts which block nephron
106
Q

How can cast nephropathy in myeloma be reversed?

A

Steroids

Chemotherapy

107
Q

What is the median age at diagnosis of myeloma?

A

65 years

108
Q

What corticosteroids are used in myeloma?

A

Dexamethasone

Prednisolone

109
Q

What alkylating agents are used in melanoma?

A

Cyclophosphamide

Melphalan

110
Q

What ‘novel’ agents are used in melanoma?

A

Thalidomide
Bortezomib
Lenalidomide

111
Q

How can response to therapy in myeloma be monitored?

A

Paraprotein level

112
Q

What analgesia is used in myeloma and what should be avoided?

A

Use opiates

Avoid NSAIDs

113
Q

What is local radiotherapy useful for in myeloma?

A

Pain relief

Spinal cord compression

114
Q

What use do bisphosphonates have in myeloma?

A

Correct hypercalcaemia

Helps bone pain

115
Q

What is a vertebroplasty?

A

Injection of sterile cement into fractured bone to stabilise

116
Q

What is the definition of Monoclonal Gammopathy of Undetermined Significance (MGUS)?

A

Paraprotein <30g/L
Bone marrow plasma cells <10%
No evidence of myeloma end organ damage

117
Q

What is Amyloid light-chain amyloidosis?

A

Small plasma cell clone
Mutation in the light chain - Altered structure
Precipitates in tissues as an insoluble beta-pleated sheet

118
Q

What organs are damaged in amyloid light-chain amyloidosis?

A 
Nephrotic syndrome
Cardiomyopathy
Organomegaly-deranged LFTs
Neuropathy (ANS and peripheral)
Malabsorption
119
Q

How is amyloid light-chain amyloidosis diagnosed?

A

Congo red stain - ‘Apple green’ birefringence
Rectal/Fat biopsy:
- If high clinical suspicion
- Less invasive

120
Q

How can evidence of organ damage be assessed in amyloid light-chain amyloidosis?

A

SAP scan
Echocardiogram
Heavy proteinuria

121
Q

What paraprotein is involved in Waldenstrom’s Macroglobulinaemia?

A

IgM

122
Q

What is Waldenstrom’s Macroglobulinaemia?

A

Lymphoplasmacytoid neoplasm:

- Clonal disorder of cells intermediate between a lymphocyte and plasma cell

123
Q

What size are the paraproteins in Waldenstrom’s Macroglobulinaemia?

A

Very large - 900KDa

124
Q

What are the tumour effects in Waldenstrom’s Macroglobulinaemia?

A

Lymphadenopathy
Splenomegaly
Marrow failure

125
Q

What are the paraprotein effects in Waldenstrom’s Macroglobulinaemia?

A

Hyperviscosity

Neuropathy

126
Q

What are the hyperviscosity effects in Waldenstrom’s Macroglobulinaemia?

A

Fatigue, visual disturbance, confusion, coma
Bleeding
Cardiac failure

127
Q

What are the B symptoms in Waldenstrom’s Macroglobulinaemia?

A

Night sweats

Weight loss

128
Q

How is Waldenstrom’s Macroglobulinaemia treated?

A

Chemotherapy
Plasmapheresis:
- Removes IgM paraprotein rich plasma
- Replace with donor plasma

129
Q

What myeloproliferative disorders are BCR-ABL1 negative?

A

Idiopathic myelofibrosis
Polycythaemia Rubra Vera
Essential thrombocythaemia

130
Q

What myeloproliferative disorder is BCR-ABL1 positive?

A

Chronic myeloid leukaemia

131
Q

What is the other name for BCR-ABL1?

A

Philadelphia chromosome

132
Q

What is chronic myeloid leukaemia?

A

Proliferation of myeloid cells:

  • Granulocytes and their precursors
  • Other lineages (platelets)
133
Q

How long is the chronic phase in CML? What occurs in this stage?

A

3-5 years

Intact maturation

134
Q

What follows the chronic phase in CML?

A

‘Blast crisis’:

- Reminiscent of acute leukaemia with maturation defect

135
Q

How is CML treated?

A

Stem cell/Bone marrow transplant

136
Q

What are the clinical features of CML?

A 
Splenomegaly
Hypermetabolic symptoms
Bleeding (in crisis)
Gout
Priapism
137
Q

What problems, related to hyperleucocytosis, can arise in CML?

A

Microcirculation occlusion:

  • Headache
  • Blurred vision
  • TIAs
  • CVAs
138
Q

What is the gene product of BCR-ABL1?

A

A tyrosine kinase:

  • Abnormal phosphorylation
  • Haematological changes
139
Q

Because of BCR-ABL1, what can durable CML respond to?

A

Tyrosine kinase inhibitors (eg. Imatinib)

140
Q

What features in MPD are due to increased cellular turnover?

A

Gout (purine turnover)
Fatigue
Weight loss
Sweats

141
Q

How does marrow failure arise in MPD?

A

Fibrosis or leukaemic transformation
Lower with:
- Polycythaemia Rubra Vera
- Essential thrombocythaemia

142
Q

What thrombotic events can occur in MPD?

A 
TIA
MI
Abdominal vessel thrombosis
Claudication
Erythromelalgia
143
Q

What is Polycythaemia Rubra Vera?

A

High Hb/Hct accompanied by erythrocytosis:

- A true increase in RBC mass

144
Q

What can cause a secondary polycythaemia?

A

Chronic hypoxia
Smoking (COPD)
Epo-secreting tumours (eg. Renal carcinoma)
Drugs (Epo, anabolic steroids, testosterone)

145
Q

What can cause pseudopolycythaemia?

A 
Dehydration
Diuretics
Obesity:
- Gaisbock syndrome (Hypertension -> Reduced plasma volume)
Burns
146
Q

What are the clinical features of polycythaemia rubra vera?

A

Features common to MPD
Headache and fatigue:
- Increased blood viscosity (not plasma viscosity)
Itch (Aquagenic pruritis)

147
Q

What mutation status should be investigated in polycythaemia rubra vera? What does its mutation result in?

A

JAK2 mutation (seen in 95%):

  • Loss of auto-inhibition
  • Erythropoiesis activated in absence of ligand
148
Q

How can secondary of pseudo- causes of polycythaemia be ruled out?

A

CXR
ABG
DHx

149
Q

How is polycythaemia rubra vera treated?

A

Venesect to haematocrit <0.45
Aspirin
Cytotoxic oral chemotherapy:
- Hydroxycarbamide

150
Q

What is essential thrombocythaemia?

A

Uncontrolled production of abnormal platelets

151
Q

Abnormal platelet function essential thrombocythaemia can cause what?

A

Thrombosis
Acquired von Willebrand disease:
- Bleeding

152
Q

What are the clinical features of essential thrombocythaemia?

A

Features common to MPD:
- Particularly vaso-occlusion
Bleeding

153
Q

What type of thrombocythaemia must be excluded for the diagnosis of essential thrombocythaemia?

A

Reactive:

  • Blood loss
  • Inflammation
  • Malignancy
  • Iron deficiency
154
Q

What cancer must be secluded before diagnosing essential thrombocythaemia?

A

CML

155
Q

What genetic mutations should be investigated for in essential thrombocythaemia?

A

JAK2 mutations (in 50%)
Calreticulin (CALR):
- In those without mutant JAK2
MPL

156
Q

How does bone marrow appear in essential thrombocythaemia?

A

Megakaryocyte hyperplasia

Increased platelets

157
Q

How is essential thrombocythaemia treated?

A 
Aspirin
Cytoreductive therapy to control proliferation:
- Hydroxycarbamide
- Anagrelide
- INF-alpha
158
Q

What is the alternate name for idiopathic myelofibrosis?

A

Agnogenic myeloid metaplasia

159
Q

What are the clinical features of idiopathic myelofibrosis?

A 
Marrow failure
Bone marrow fibrosis
Extramedullary haematopoiesis:
- Liver
- Spleen
Leukoerythroblastic film appearance:
- Tear drop RBCs
- Metamyelocytes, myelocytes, promyelocytes, myeloblasts and nucleated RBCs
160
Q

What are some secondary causes of myelofibrosis?

A

Post-polycythaemia

Essential thrombocythaemia

161
Q

What are the splenomegaly features in myelofibrosis?

A

LUQ abdominal pain

Portal hypertension

162
Q

Apart from the typical blood film features of myelofibrosis, how else can it be diagnosed?

A

Dry bone marrow aspirate
Fibrosis on trephine biopsy
JAK2 or CALR mutation in some

163
Q

How is myelofibrosis treated?

A

Supportive care
Allogenic stem cell transplant
Splenectomy
JAK2 inhibitors

164
Q

What can cause a reactive granulocyte change?

A 
Infection:
- Eg. Neutophilia in pyogenic bacteria
Physiological:
- Post surgery
- Steroids
165
Q

What can cause a reactive thrombocythaemia?

A

Infection
Iron deficiency
Malignancy
Blood loss

166
Q

What can cause a reactive polycythaemia?

A 
Dehydration
Secondary polycythaemia (eg. Hypoxia)
167
Q

What are the general characteristics of cell-cycle specific chemotherapy agents?

A 
Tumour specific (relatively)
Duration of exposure more important than dose
168
Q

What are the groups of cell-cycle specific chemotherapy agents?

A

Antimetabolits:
- Impair nucleotide synthesis/incorporation
Mitotic spindle inhibitors

169
Q

What class of drugs does methotrexate belong to?

A

Antimetabolites

170
Q

How does methotrexate work?

A

Inhibits dihydrofolate reductase

171
Q

How do the following antimetabolites work:

  • 6-Mercaptopurine
  • Cytosine arabinoside
  • Fludarabine
A

Incorporated into DNA

172
Q

How does hydroxyurea work?

A

Impairs deoxynucleotide synthesis:

- By inhibiting ribonucleotide reductase

173
Q

What is the other name for hydroxyurea?

A

Hydroxycarbamide

174
Q

What enzyme is responsible for unwinding DNA for new DNA strand synthesis?

A

Topoisomerase II

175
Q

What are some examples of mitotic spindle inhibitors?

A

Vinca alkaloids:
- Vincristine
- Vinblastine
Docetaxel (A taxone)

176
Q

What are the general characteristics of non-cell cycle specific agents?

A

Non-tumour specific:
- Damages normal stem cells
Cumulative dose more important than duration

177
Q

What group of drugs do chlorambucil and melphalan belong to?

A

Alkylating agents (non-cell cycle specific)

178
Q

How do chlorambucil and melphalan work?

A

Bind covalently to bases of DNA (adducts)
Produces DNA strand breaks (mutation):
- By free radical production

179
Q

What group of drugs do cisplatin and carboplatin belong to?

A

Platinum derivatives (non-cell cycle specific)

180
Q

What group of drugs do daunorubicin, doxorubicin and idarubicin belong to?

A

Cytotoxic antibiotics - Anthracyclines (non-cell cycle specific)

181
Q

How do anthracycline antibiotics work?

A 
DNA intercalation (reversible)
Impairs RNA transcription
Strand breaks in DNA due to free radicals
182
Q

What organs does chemotherapy tend to affect?

A

Rapidly dividing organs:

  • Bone marrow suppression
  • Gut mucosal damage
  • Hair loss (alopecia)
183
Q

What is a specific side effect of vinca alkaloids?

A

Neuropathy (usually peripheral)

184
Q

What is a specific side effect of cytosine arabinoside?

A

Cerebellar toxicity (ataxia)

185
Q

What is a specific side effect of methotrexate?

A

Hepatotoxicity

186
Q

What is a specific side effect of anthracyclines?

A

Cardiotoxicity:

  • Arrhythmias
  • Cardiomyopathy
  • Heart failure
187
Q

What are some specific side effects of cisplatin?

A

Nephrotoxicity

and neurotoxicity

188
Q

What are some long term side effects of alkylating agents?

A

Infertility

Secondary malignancy

189
Q

What can result in resistance to cyclophosphamide?

A

Altered drug (pro-drug) metabolism

190
Q

What can result in cisplatin resistance?

A

Increased DNA repair

191
Q

Myelosuppression can occur during chemotherapy, which restricts the ability to intensify chemo. How can this be overcome?

A

Use of haematopoietic growth factors
Combine myelosuppressive/non-myelosuppressive agents
Intensify doses of active drugs

192
Q

What do p53 mutations in CLL result in?

A

More difficult to treat by chemotherapy and radiotherapy

193
Q

What can too high a dose of chemotherapy or radiotherapy result in?

A

Necrosis
Cell swells
Plasma membrane ruptures
Cellular and nuclear lysis causes inflammation

194
Q

Why do blood cancers respond better to chemotherapy and radiotherapy?

A

Lymphocytes keen to undergo apoptosis in normal LNs
Lymphoma and CLL cells can be triggered to undergo apoptosis readily
Acute leukaemia:
- Cells divide very quickly
- More cells dividing (affected more by chemo)

195
Q

What antifungals can be used prophylactically during chemotherapy and radiotherapy?

A

Itraconazole

Posaconazole

196
Q

What is the risk-adapted therapy in Hodgkin’s Lymphoma?

A

ABVD:

  • Adriamycin (aka Doxorubicin)
  • Bleomycin
  • Vincristine
  • Dacarbazine
197
Q

How are side effects avoided in the risk-adapted therapy in Hodgkin’s Lymphoma?

A

Dropping bleomycin in cycles 3-6

198
Q

If a PET was still positive after the initial 6 cycles of risk-adapted therapy in Hodgkin’s Lymphoma, what could be done?

A

Escalate therapy to BEACOPP:

  • Bleomycin
  • Etoposide
  • Adriamycin (aka Doxorubicin)
  • Cyclophosphamide
  • Oncovin (aka Vincristine)
  • Procarbazine
  • Prednisolone
199
Q

Where does Rituximab bind?

A

CD20 on B-cells

200
Q

What therapy regime increases responses and cures in high-grade B-cell NHL?

A

RCHOP:

  • Rituximab
  • Cyclophosphamide
  • Hydroxydaunorubicin (aka Doxorubicin)
  • Oncovin (aka Vincristine)
  • Prednisone (or Prednisolone)
201
Q

How is rituximab administered?

A

5 minute S/C injection instead of IV

202
Q

What are ofatunumab and obinutumab (other anti-B-cell Abs) better than rituximab in?

A

CLL in less fit patients
?NHL
Patients not responding to rituximab

203
Q

What is Brentuximab Vedotin and what is it useful for?

A

An anti-CD30 Ab with a chemo drug tagged on:

  • Hodgkin’s lymphoma
  • Some T-cell NHL
204
Q

What are the side effects of Brentuximab Vedotin?

A

Nerve damage
Neutropaenia
Fatigue +++

205
Q

What are some examples of biological therapies for myeloma (and possible lymphoma)?

A

Proteosome inhibitors

IMIDs

206
Q

What type of drug is Bortezomib and what can it be used in?

A

Proteosome inhibitor:

  • Mantle cell NHL
  • Low grade NHL (eg. Waldenstroms)
207
Q

What are some side effects of proteosome inhibitors?

A

Nerve damage

Thrombocytopaenia

208
Q

What class of drugs does Lenalidomide belong to?

A

Immunomodulatory Imide Drugs (IMIDs)

209
Q

What can IMIDs be used in?

A

Low-grade NHL
CLL
Myeloma

210
Q

What are some side effects of IMIDs?

A

Nerve damage
Teratogenicity
Anaemia and thrombocytopaenia
Other cancers (esp. AML)

211
Q

What do Ibrutinib and Idelalisib do?

A

Target malignant B-cells:

  • CLL
  • NHL
212
Q

What does Nivolumab do?

A

Stop tumours evading immune system

213
Q

What molecular/targeted treatments can be used in CML?

A

Tyrosine kinase inhibitors

214
Q

What are some examples of tyrosine kinase inhibitors?

A

Imatinib
Nilotinib
Dasatinib
Ponatinib

215
Q

What are the side effects of tyrosine kinase inhibitors?

A

Diarrhoea
Pulmonary oedema
Neutropaenia

216
Q

What is Idelalisib approved in?

A

CLL with p53 mutation

217
Q

What are the side effects of Idelalisib?

A 
Diarrhoea
Rash
Fatigue
Liver abnormality
Fever
218
Q

What are the side effects of Ibrutinib?

A

Fever
Thrombocytopaenia
Anaemia
Shortness of breath

219
Q

What can Nivolumab be used in?

A

Malignant melanoma

Hodgkin’s lymphoma

220
Q

How do cancer cells evade the immune system?

A

Produce chemicals which bind to PD-1 receptor:

  • Immune cell switched off
  • ‘Ignores’ tumour
221
Q

What is the most promising adaptive immunotherapy?

A

Chimeric Antigen Receptor T cells therapy

222
Q

How does CAR T therapy work?

A
  1. T-cells harvested
  2. Ag receptors added
  3. Cells allowed to multiply
  4. Infused back into patient
223
Q

What cancers does CAR T work in?

A

ALL

B-cell NHL

224
Q

What is the lifespan of a neutrophil?

A

~7-8 hours

225
Q

During development, when can circulating committed progenitors be detected?

A

Week 5

226
Q

When does the yolk sac stop haematopoiesis in the embryo?

A

Week 10

227
Q

When does the liver start haematopoiesis in the embryo?

A

Week 6

228
Q

When does the spleen start haematopoiesis in the embryo?

A

Week 12

229
Q

When does the bone marrow start haematopoiesis in the embryo?

A

Week 16

230
Q

What is the release of RBCs associated with in the bone marrow?

A

Sinusoidal dilatation

Increased blood flow

231
Q

How can the cellularity of bone marrow be approximated?

A

100 - Age = Cellularity (%)

232
Q

What regulates neutrophil maturation?

A

Granulocyte-colony stimulating factor

233
Q

What regulates the growth and development of megakaryocytes?

A

Thrombopoietin

234
Q

What are the peripheral (Secondary) lymphoid tissues?

A 
Lymph nodes
Spleen
Tonsils (Waldeyer's ring)
Epitheliolymphoid tissues
Bone marrow
235
Q

How much does a spleen usually weigh?

A

150-200g

236
Q

What are the dimensions of a normal spleen

A

12x7x3cm

237
Q

What does the visceral aspect of the spleen touch?

A

Left kidney
Gastric fundus
Tail of pancreas
Splenic flexure of colon

238
Q

What does the red pulp of the spleen contain?

A

Sinusoids

Cords

239
Q

What is the structure of splenic sinusoids?

A

Fenestrated
Lined by endothelial cells
Supported by hoops of reticulin

240
Q

What do the cords in splenic red pulp contain?

A

Macrophages
Some fibroblasts
Cells in transit

241
Q

What arteries does the splenic artery give off?

A

Trabecular arteries

242
Q

What do the branches of the splenic artery become when they reach the white pulp? What do they give off to the perilymphoid sinuses?

A

Central arteries:

- Give off radial arteries

243
Q

What happens to the central arteries when they branch off to the red pulp?

A

Penicillary arteries

244
Q

How does blood drain from the spleen into the splenic vein?

A

Trabecular veins

245
Q

What does the white pulp comprise?

A

Periarteriolar lymphoid sheath:

- CD4+ cells

246
Q

What forms the malpighian corpuscles?

A

Periarteriolar lymphoid sheath

Lymphoid follicles

247
Q

How does splenic enlargement present?

A

Dragging sensation in LUQ
Discomfort with eating
Pain (if infarction)

248
Q

What is hypersplenism a triad of?

A

Splenomegaly
Fall in >=1 cellular components of blood
Correction of cytopaenias by splenectomy

249
Q

What is the most common cause of hyposplenism?

A

Splenectomy

250
Q

What conditions can cause hyposplenism?

A

Coeliac disease
Sickle cell disease
Sarcoidosis
Iatrogenic

251
Q

What causes the features of hyposplenism?

A

Reduced red pulp function

252
Q

What does a blood film show in hyposplenism?

A

Howell-Jolly bodies:
- Basophilic nuclear remnants in RBCs
Other RBC abnormalities

Year 3 - Haematology (DP) (3 decks)

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