Haematopoiesis, White Cells + Their Disorders Flashcards
(252 cards)
1
Q
How can mature blood cells be identified?
A
Morphology
Cell surface antigens
Enzyme expression
2
Q
How can progenitors and stem cells be identified?
A
Cell surface antigens
Cell culture assays
Animal models
3
Q
What cell surface antigen is present on RBCs?
A
Glycophorin A
4
Q
What enzyme is expressed in Neutrophils?
A
Myeloperoxidase
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
6
Q
What are ‘driver mutations’?
A
Confer growth advantage
Positively selected during cell evolution
7
Q
What are ‘passenger mutations’?
A
No growth advantage
Present in ancestor when it acquired its driver
8
Q
What is a clone?
A
A population of cells derived from a single parent cell
9
Q
What is the clonality of normal haematopoiesis?
A
Polyclonal
10
Q
What is the clonality of malignant haematopoiesis?
A
Monoclonal
11
Q
What are the features of a ‘high-grade’ lymphoma?
A
Aggressive histology (large primitive cells) Aggressive clinical features
12
Q
What is a myeloma?
A
Plasma cell malignancy in marrow
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
14
Q
What are the classifications of acute lymphoblastic leukaemia?
A
Precursor B cell
Precursor T cell
B cell:
- Burkitt’s lymphoma/leukaemia
15
Q
Why causes acute lymphoblastic leukaemia to present?
A
Marrow failure: - Anaemia - Infections - Bleeding Bone pain
16
Q
What are the leukaemic effects in ALL?
A
High WCC
Involvement of extramedullary areas
Venous obstruction (due to LNs)
17
Q
Who is acute myelogenous leukaemia more common in?
A
Elderly (>60)
18
Q
What chromosomal translocation is seen in acute promyelocytic leukaemia?
A
t(15;17)
19
Q
How can acute promyelocytic leukaemia present?
A
DIC
20
Q
How does AML present?
A
Similar to ALL (marrow failure) Gum infiltration (in some subgroups)
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
22
Q
What are Auer rods and what are they seen in?
A
Red-staining ‘needles’ in cytoplasm of myeloblasts
Seen in AML
23
Q
How can a definitive diagnosis of acute leukaemia be made?
A
Bone marrow for immunophenotyping:
- Expression of lineage-associated proteins
24
Q
What is a trephine and when is it useful?
A
Piece of bone
When bone marrow aspirate is sub-optimal
25
How long can chemotherapy in ALL last?
2-3 years
26
What are the phases of chemotherapy in ALL?
1. Induction
2. Consolidation
3. Maintenance
27
What is a typical cycle of chemotherapy in AML?
5-10 days of chemo following by 2-4 weeks of recovery
| Total 2-4 cycles
28
What are the problems related to marrow suppression?
Anaemia
Neutropaenia
Thrombocytopaenia
29
What bacteria tend to cause infections in marrow suppression due to neutropaenia?
Gram negative bacteria:
| - Fulminant, life-threatening sepsis
30
What does thrombocytopaenia result in?
Bleeding:
- Purpura
- Petechiae (platelets <20x10^9)
31
What is tumour lysis syndrome?
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
32
How does tumour lysis syndrome present?
Symptoms/signs related to:
- Hyperkalaemia
- Hyperphosphataemia
- Hypocalcaemia
- Hyperuricaemia
- High blood urea nitrogen
33
When should a fungal infection (during leukaemia treatment) be suspected?
Prolonged neutopaenia
| Persisting fever unresponsive to ABx
34
When is protozoal (eg. PJP) infection more relevant?
ALL therapy
35
What are the long term complications of leukaemia therapy?
Loss of fertility
| Cardiomyopathy (with anthracyclines)
36
What is the cure rate in childhood ALL?
>85-90%
37
When can an allogenic stem cell transplant be used in leukaemia?
After initial therapy
| At relapse
38
What is blinatumomab?
Bi-specific T cell enhancer
39
What are the differentials for night sweats?
Lymphoma
Infection
Menopause
40
What are the differentials for weight loss?
Lymphoma
Other malignancy
Infections
41
What are the symptoms of lymphoma?
```
A 'lump'
General symptoms
Itch without a rash
Alcohol-induced pain
Fatigue
```
42
How does a 'lump' feel in lymphoma?
```
Non-tender
Rubbery-Soft
Smooth
No skin inflammation
Not tethered
```
43
How useful is a CT in lymphoma?
Not useful
44
What CD number is seen in follicular NHL?
CD20+ cells
45
What CD number is seen in Hodgkin's Lymphoma?
CD30+ Reed Sternberg Cells
46
In what patients is immunophenotyping useful?
Leukaemia
Lymphomas involving marrow:
- eg. Burkitt's Lymphoma
47
What genetic change is seen in follicular NHL?
t(14;18)
48
What genetic change is seen in mantle cell NHL?
t(11;14)
49
What drug does activated B cell type NHL respond well to?
Ibrutinib
50
What is the most common group of lymphomas?
B-cell NHL
51
```
What do the following indicate:
- Short stature
- Skin pigment abnormalities (inc. cafe au lait)
- Radial ray abnormalities
- Hypogenitalia
- Endocrinopathies
How is it inherited?
```
Fanconi's anaemia
| Autosomal recessive
52
How do inherited marrow failure syndromes arise?
Unable to correct inter-strand crosslinks resulting in DNA damage
53
What FBC changes are seen in inherited marrow failure syndromes?
Macrocytosis
Followed by:
- Thrombocytopaenia
- Then neutropaenia
54
What is the median age of onset of haematological abnormalities in inherited marrow failure syndromes?
7 years
55
What is the pathophysiology behind aplastic anaemia?
```
Autoreactive T cells produce IFN-gamma and TNF-alpha against:
- LT-HSCs
- MPPs
- CMPs
Results in reduced production of:
- RBCs
- Platelets
- Granulocytes
```
56
What are the features of myelodysplastic syndrome?
Dysplasia
Hypercellular marrow
Increased apoptosis of progenitor and mature cells
57
What can myelodysplastic syndrome evolve into?
AML
58
What drugs can induce secondary bone marrow failure (aplasia)?
Chemotherapy
Chloramphenicol
Alcohol
59
What can cause hypersplenism?
```
Splenic congestion:
- Portal hypertension
- CCF
Systemic diseases:
- RA (Felty's)
Haematological diseases:
- Splenic lymphoma
```
60
Apart from drugs, what other causes are there of secondary bone marrow failure?
B12/Folate deficiency
Infiltration
Miscellaneous
61
What is the cellularity of bone marrow in aplastic anaemia?
Hypocellular
62
What are some causes of hypercellular bone marrow in regards to pancytopaenia?
MDS
B12/Folate deficiency (eg. Megaloblastic anaemia)
Hypersplenism
(Malignant infiltration - Only gives a hypercellular appearance)
63
What are the possible variants of the heavy chains in immunoglobulins?
```
mew
alpha
delta
gamma
epsilon
```
64
What are the possible variants of the light chains in immunoglobulins?
kappa
| lambda
65
What is the part at the end of both the heavy chains and light chains in immunoglobulins?
Variable region
66
What part of the immunoglobulin does an antigen bind to?
The antigen binding site in the Fab region of the Ab
67
What part of the immunoglobulin forms the tail and binds to cell receptors?
Fc region
68
What immunoglobulins are typically monomers?
IgD
IgE
IgG
69
What immunoglobulin is a dimer?
IgA
70
What immunoglobulin is a pentamer?
IgM
71
Where is the Ig variable element generated from?
V-D-J region recombination early in development
72
What cells are removed during B-cell development?
Self-reactive
73
When happens to B cells in the periphery?
Follicle germinal centre of LN:
- Identify Ag and improve fit or
- Be deleted
74
What happens to a B cell after it is processed in the LN?
Return to marrow as a plasma cell
OR
Circulate as a memory cell
75
How does a plasma cell nucleus appear? Why?
Eccentric 'clock-face' nucleus on H+E stain:
| - Open chromatin synthesising mRNA
76
How does a plasma cell appear?
Plentiful blue cytoplasm (laden with protein)
| Pale perinuclear area (golgi)
77
What is a paraprotein?
Abnormal, monoclonal IG fragments or IG light chains
78
What is a paraprotein a marker of?
Underlying clonal B-cell disorder
79
From anode (+) to cathode (-), how do the following separated serum proteins appear?
- Beta
- Alpha-1
- Alpha-2
- Albumin
- Gamma
```
Albumin
Alpha-1
Alpha-2
Beta
Gamma
```
80
What is the main component of the Alpha-1 band/zone in serum electrophoresis?
Alpha-1 antitrypsin
81
What are the main components of the Alpha-2 band/zone in serum electrophoresis?
Alpha-2 macroglobulin
Caeruloplasmin
Haptoglobin
82
What are the main components of the Beta band/zone in serum electrophoresis?
Transferrin
Low density lipoprotein
C3
83
What are the main components of the Gamma band/zone in serum electrophoresis?
Immunoglobulins
84
What do the groupings of serum electrophoresis indicate?
Their mobility (not their functioning)
85
What is the purpose of serum immunofixation?
To classify the abnormal protein band
86
What is Bence-Jones protein?
Unusual protein precipitate found on warming urine which re-dissolves when heated
87
What were Bence-Jones proteins later identified as?
Ig light chains
88
How are Bence-Jones proteins detected?
Urine electrophoresis
89
What happens when immunoglobulins are made by plasma cells?
More light chains made than heavy chains:
| - Free light chains secreted into plasma
90
How many free light chains are secreted into the plasma per day?
0.5g/day
91
What free light chains are monomeric?
kappa
92
What free light chains are dimeric?
lambda
93
What can cause an increased amount of free light chains?
Polyclonal increase in plasma cells (infection)
| Monoclonal increase in plasma cells (myeloma)
94
What direct tumour cell effects can myeloma cause?
```
Bone lesions
Increased calcium
Bone pain
Replace normal bone marrow:
- Marrow failure
```
95
What are the paraprotein mediated effects in myeloma?
Renal failure
Immune suppression
Hyperviscosity
Amyloid
96
What is the most common paraprotein produced in myeloma?
IgG
97
What is the least common paraprotein produced in myeloma?
IgE
98
When myeloma cells activate the RANKL receptors on bone marrow stromal cells what happens?
IL-6 is produced
99
When IL-6 is produced, what is produced and what cells are affected?
IL-6 levels are increased substantially
TGF-beta levels are increased
Osteoblasts are suppressed
Osteoclasts are activated
100
What happens when osteoclasts are activated in myeloma?
Hyeprcalcaemia
101
What bone lesions are seen in myeloma?
Lytic:
| - Plain radiographs may show 'punched-out' lesions
102
What can bone lesions in myeloma result in?
Wedge compression spinal fractures
103
How much paraprotein can the PCT in the kidney reabsorb and catabolise per day?
10-30g
104
What happens, in regard to paraproteins, if the PCT is damaged or overwhelmed?
Paraproteins enter the Loop of Henle
105
What is produced when paraproteins enter the ascending limb of the Loop of Henle?
Tamm-Horsfall protein:
- Combines with paraproteins
- Insoluble casts which block nephron
106
How can cast nephropathy in myeloma be reversed?
Steroids
| Chemotherapy
107
What is the median age at diagnosis of myeloma?
65 years
108
What corticosteroids are used in myeloma?
Dexamethasone
| Prednisolone
109
What alkylating agents are used in melanoma?
Cyclophosphamide
| Melphalan
110
What 'novel' agents are used in melanoma?
Thalidomide
Bortezomib
Lenalidomide
111
How can response to therapy in myeloma be monitored?
Paraprotein level
112
What analgesia is used in myeloma and what should be avoided?
Use opiates
| Avoid NSAIDs
113
What is local radiotherapy useful for in myeloma?
Pain relief
| Spinal cord compression
114
What use do bisphosphonates have in myeloma?
Correct hypercalcaemia
| Helps bone pain
115
What is a vertebroplasty?
Injection of sterile cement into fractured bone to stabilise
116
What is the definition of Monoclonal Gammopathy of Undetermined Significance (MGUS)?
Paraprotein <30g/L
Bone marrow plasma cells <10%
No evidence of myeloma end organ damage
117
What is Amyloid light-chain amyloidosis?
Small plasma cell clone
Mutation in the light chain - Altered structure
Precipitates in tissues as an insoluble beta-pleated sheet
118
What organs are damaged in amyloid light-chain amyloidosis?
```
Nephrotic syndrome
Cardiomyopathy
Organomegaly-deranged LFTs
Neuropathy (ANS and peripheral)
Malabsorption
```
119
How is amyloid light-chain amyloidosis diagnosed?
Congo red stain - 'Apple green' birefringence
Rectal/Fat biopsy:
- If high clinical suspicion
- Less invasive
120
How can evidence of organ damage be assessed in amyloid light-chain amyloidosis?
SAP scan
Echocardiogram
Heavy proteinuria
121
What paraprotein is involved in Waldenstrom's Macroglobulinaemia?
IgM
122
What is Waldenstrom's Macroglobulinaemia?
Lymphoplasmacytoid neoplasm:
| - Clonal disorder of cells intermediate between a lymphocyte and plasma cell
123
What size are the paraproteins in Waldenstrom's Macroglobulinaemia?
Very large - 900KDa
124
What are the tumour effects in Waldenstrom's Macroglobulinaemia?
Lymphadenopathy
Splenomegaly
Marrow failure
125
What are the paraprotein effects in Waldenstrom's Macroglobulinaemia?
Hyperviscosity
| Neuropathy
126
What are the hyperviscosity effects in Waldenstrom's Macroglobulinaemia?
Fatigue, visual disturbance, confusion, coma
Bleeding
Cardiac failure
127
What are the B symptoms in Waldenstrom's Macroglobulinaemia?
Night sweats
| Weight loss
128
How is Waldenstrom's Macroglobulinaemia treated?
Chemotherapy
Plasmapheresis:
- Removes IgM paraprotein rich plasma
- Replace with donor plasma
129
What myeloproliferative disorders are BCR-ABL1 negative?
Idiopathic myelofibrosis
Polycythaemia Rubra Vera
Essential thrombocythaemia
130
What myeloproliferative disorder is BCR-ABL1 positive?
Chronic myeloid leukaemia
131
What is the other name for BCR-ABL1?
Philadelphia chromosome
132
What is chronic myeloid leukaemia?
Proliferation of myeloid cells:
- Granulocytes and their precursors
- Other lineages (platelets)
133
How long is the chronic phase in CML? What occurs in this stage?
3-5 years
| Intact maturation
134
What follows the chronic phase in CML?
'Blast crisis':
| - Reminiscent of acute leukaemia with maturation defect
135
How is CML treated?
Stem cell/Bone marrow transplant
136
What are the clinical features of CML?
```
Splenomegaly
Hypermetabolic symptoms
Bleeding (in crisis)
Gout
Priapism
```
137
What problems, related to hyperleucocytosis, can arise in CML?
Microcirculation occlusion:
- Headache
- Blurred vision
- TIAs
- CVAs
138
What is the gene product of BCR-ABL1?
A tyrosine kinase:
- Abnormal phosphorylation
- Haematological changes
139
Because of BCR-ABL1, what can durable CML respond to?
Tyrosine kinase inhibitors (eg. Imatinib)
140
What features in MPD are due to increased cellular turnover?
Gout (purine turnover)
Fatigue
Weight loss
Sweats
141
How does marrow failure arise in MPD?
Fibrosis or leukaemic transformation
Lower with:
- Polycythaemia Rubra Vera
- Essential thrombocythaemia
142
What thrombotic events can occur in MPD?
```
TIA
MI
Abdominal vessel thrombosis
Claudication
Erythromelalgia
```
143
What is Polycythaemia Rubra Vera?
High Hb/Hct accompanied by erythrocytosis:
| - A true increase in RBC mass
144
What can cause a secondary polycythaemia?
Chronic hypoxia
Smoking (COPD)
Epo-secreting tumours (eg. Renal carcinoma)
Drugs (Epo, anabolic steroids, testosterone)
145
What can cause pseudopolycythaemia?
```
Dehydration
Diuretics
Obesity:
- Gaisbock syndrome (Hypertension -> Reduced plasma volume)
Burns
```
146
What are the clinical features of polycythaemia rubra vera?
Features common to MPD
Headache and fatigue:
- Increased blood viscosity (not plasma viscosity)
Itch (Aquagenic pruritis)
147
What mutation status should be investigated in polycythaemia rubra vera? What does its mutation result in?
JAK2 mutation (seen in 95%):
- Loss of auto-inhibition
- Erythropoiesis activated in absence of ligand
148
How can secondary of pseudo- causes of polycythaemia be ruled out?
CXR
ABG
DHx
149
How is polycythaemia rubra vera treated?
Venesect to haematocrit <0.45
Aspirin
Cytotoxic oral chemotherapy:
- Hydroxycarbamide
150
What is essential thrombocythaemia?
Uncontrolled production of abnormal platelets
151
Abnormal platelet function essential thrombocythaemia can cause what?
Thrombosis
Acquired von Willebrand disease:
- Bleeding
152
What are the clinical features of essential thrombocythaemia?
Features common to MPD:
- Particularly vaso-occlusion
Bleeding
153
What type of thrombocythaemia must be excluded for the diagnosis of essential thrombocythaemia?
Reactive:
- Blood loss
- Inflammation
- Malignancy
- Iron deficiency
154
What cancer must be secluded before diagnosing essential thrombocythaemia?
CML
155
What genetic mutations should be investigated for in essential thrombocythaemia?
JAK2 mutations (in 50%)
Calreticulin (CALR):
- In those without mutant JAK2
MPL
156
How does bone marrow appear in essential thrombocythaemia?
Megakaryocyte hyperplasia
| Increased platelets
157
How is essential thrombocythaemia treated?
```
Aspirin
Cytoreductive therapy to control proliferation:
- Hydroxycarbamide
- Anagrelide
- INF-alpha
```
158
What is the alternate name for idiopathic myelofibrosis?
Agnogenic myeloid metaplasia
159
What are the clinical features of idiopathic myelofibrosis?
```
Marrow failure
Bone marrow fibrosis
Extramedullary haematopoiesis:
- Liver
- Spleen
Leukoerythroblastic film appearance:
- Tear drop RBCs
- Metamyelocytes, myelocytes, promyelocytes, myeloblasts and nucleated RBCs
```
160
What are some secondary causes of myelofibrosis?
Post-polycythaemia
| Essential thrombocythaemia
161
What are the splenomegaly features in myelofibrosis?
LUQ abdominal pain
| Portal hypertension
162
Apart from the typical blood film features of myelofibrosis, how else can it be diagnosed?
Dry bone marrow aspirate
Fibrosis on trephine biopsy
JAK2 or CALR mutation in some
163
How is myelofibrosis treated?
Supportive care
Allogenic stem cell transplant
Splenectomy
JAK2 inhibitors
164
What can cause a reactive granulocyte change?
```
Infection:
- Eg. Neutophilia in pyogenic bacteria
Physiological:
- Post surgery
- Steroids
```
165
What can cause a reactive thrombocythaemia?
Infection
Iron deficiency
Malignancy
Blood loss
166
What can cause a reactive polycythaemia?
```
Dehydration
Secondary polycythaemia (eg. Hypoxia)
```
167
What are the general characteristics of cell-cycle specific chemotherapy agents?
```
Tumour specific (relatively)
Duration of exposure more important than dose
```
168
What are the groups of cell-cycle specific chemotherapy agents?
Antimetabolits:
- Impair nucleotide synthesis/incorporation
Mitotic spindle inhibitors
169
What class of drugs does methotrexate belong to?
Antimetabolites
170
How does methotrexate work?
Inhibits dihydrofolate reductase
171
How do the following antimetabolites work:
- 6-Mercaptopurine
- Cytosine arabinoside
- Fludarabine
Incorporated into DNA
172
How does hydroxyurea work?
Impairs deoxynucleotide synthesis:
| - By inhibiting ribonucleotide reductase
173
What is the other name for hydroxyurea?
Hydroxycarbamide
174
What enzyme is responsible for unwinding DNA for new DNA strand synthesis?
Topoisomerase II
175
What are some examples of mitotic spindle inhibitors?
Vinca alkaloids:
- Vincristine
- Vinblastine
Docetaxel (A taxone)
176
What are the general characteristics of non-cell cycle specific agents?
Non-tumour specific:
- Damages normal stem cells
Cumulative dose more important than duration
177
What group of drugs do chlorambucil and melphalan belong to?
Alkylating agents (non-cell cycle specific)
178
How do chlorambucil and melphalan work?
Bind covalently to bases of DNA (adducts)
Produces DNA strand breaks (mutation):
- By free radical production
179
What group of drugs do cisplatin and carboplatin belong to?
Platinum derivatives (non-cell cycle specific)
180
What group of drugs do daunorubicin, doxorubicin and idarubicin belong to?
Cytotoxic antibiotics - Anthracyclines (non-cell cycle specific)
181
How do anthracycline antibiotics work?
```
DNA intercalation (reversible)
Impairs RNA transcription
Strand breaks in DNA due to free radicals
```
182
What organs does chemotherapy tend to affect?
Rapidly dividing organs:
- Bone marrow suppression
- Gut mucosal damage
- Hair loss (alopecia)
183
What is a specific side effect of vinca alkaloids?
Neuropathy (usually peripheral)
184
What is a specific side effect of cytosine arabinoside?
Cerebellar toxicity (ataxia)
185
What is a specific side effect of methotrexate?
Hepatotoxicity
186
What is a specific side effect of anthracyclines?
Cardiotoxicity:
- Arrhythmias
- Cardiomyopathy
- Heart failure
187
What are some specific side effects of cisplatin?
Nephrotoxicity
| and neurotoxicity
188
What are some long term side effects of alkylating agents?
Infertility
| Secondary malignancy
189
What can result in resistance to cyclophosphamide?
Altered drug (pro-drug) metabolism
190
What can result in cisplatin resistance?
Increased DNA repair
191
Myelosuppression can occur during chemotherapy, which restricts the ability to intensify chemo. How can this be overcome?
Use of haematopoietic growth factors
Combine myelosuppressive/non-myelosuppressive agents
Intensify doses of active drugs
192
What do p53 mutations in CLL result in?
More difficult to treat by chemotherapy and radiotherapy
193
What can too high a dose of chemotherapy or radiotherapy result in?
Necrosis
Cell swells
Plasma membrane ruptures
Cellular and nuclear lysis causes inflammation
194
Why do blood cancers respond better to chemotherapy and radiotherapy?
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
What antifungals can be used prophylactically during chemotherapy and radiotherapy?
Itraconazole
| Posaconazole
196
What is the risk-adapted therapy in Hodgkin's Lymphoma?
ABVD:
- Adriamycin (aka Doxorubicin)
- Bleomycin
- Vincristine
- Dacarbazine
197
How are side effects avoided in the risk-adapted therapy in Hodgkin's Lymphoma?
Dropping bleomycin in cycles 3-6
198
If a PET was still positive after the initial 6 cycles of risk-adapted therapy in Hodgkin's Lymphoma, what could be done?
Escalate therapy to BEACOPP:
- Bleomycin
- Etoposide
- Adriamycin (aka Doxorubicin)
- Cyclophosphamide
- Oncovin (aka Vincristine)
- Procarbazine
- Prednisolone
199
Where does Rituximab bind?
CD20 on B-cells
200
What therapy regime increases responses and cures in high-grade B-cell NHL?
RCHOP:
- Rituximab
- Cyclophosphamide
- Hydroxydaunorubicin (aka Doxorubicin)
- Oncovin (aka Vincristine)
- Prednisone (or Prednisolone)
201
How is rituximab administered?
5 minute S/C injection instead of IV
202
What are ofatunumab and obinutumab (other anti-B-cell Abs) better than rituximab in?
CLL in less fit patients
?NHL
Patients not responding to rituximab
203
What is Brentuximab Vedotin and what is it useful for?
An anti-CD30 Ab with a chemo drug tagged on:
- Hodgkin's lymphoma
- Some T-cell NHL
204
What are the side effects of Brentuximab Vedotin?
Nerve damage
Neutropaenia
Fatigue +++
205
What are some examples of biological therapies for myeloma (and possible lymphoma)?
Proteosome inhibitors
| IMIDs
206
What type of drug is Bortezomib and what can it be used in?
Proteosome inhibitor:
- Mantle cell NHL
- Low grade NHL (eg. Waldenstroms)
207
What are some side effects of proteosome inhibitors?
Nerve damage
| Thrombocytopaenia
208
What class of drugs does Lenalidomide belong to?
Immunomodulatory Imide Drugs (IMIDs)
209
What can IMIDs be used in?
Low-grade NHL
CLL
Myeloma
210
What are some side effects of IMIDs?
Nerve damage
Teratogenicity
Anaemia and thrombocytopaenia
Other cancers (esp. AML)
211
What do Ibrutinib and Idelalisib do?
Target malignant B-cells:
- CLL
- NHL
212
What does Nivolumab do?
Stop tumours evading immune system
213
What molecular/targeted treatments can be used in CML?
Tyrosine kinase inhibitors
214
What are some examples of tyrosine kinase inhibitors?
Imatinib
Nilotinib
Dasatinib
Ponatinib
215
What are the side effects of tyrosine kinase inhibitors?
Diarrhoea
Pulmonary oedema
Neutropaenia
216
What is Idelalisib approved in?
CLL with p53 mutation
217
What are the side effects of Idelalisib?
```
Diarrhoea
Rash
Fatigue
Liver abnormality
Fever
```
218
What are the side effects of Ibrutinib?
Fever
Thrombocytopaenia
Anaemia
Shortness of breath
219
What can Nivolumab be used in?
Malignant melanoma
| Hodgkin's lymphoma
220
How do cancer cells evade the immune system?
Produce chemicals which bind to PD-1 receptor:
- Immune cell switched off
- 'Ignores' tumour
221
What is the most promising adaptive immunotherapy?
Chimeric Antigen Receptor T cells therapy
222
How does CAR T therapy work?
1. T-cells harvested
2. Ag receptors added
3. Cells allowed to multiply
4. Infused back into patient
223
What cancers does CAR T work in?
ALL
| B-cell NHL
224
What is the lifespan of a neutrophil?
~7-8 hours
225
During development, when can circulating committed progenitors be detected?
Week 5
226
When does the yolk sac stop haematopoiesis in the embryo?
Week 10
227
When does the liver start haematopoiesis in the embryo?
Week 6
228
When does the spleen start haematopoiesis in the embryo?
Week 12
229
When does the bone marrow start haematopoiesis in the embryo?
Week 16
230
What is the release of RBCs associated with in the bone marrow?
Sinusoidal dilatation
| Increased blood flow
231
How can the cellularity of bone marrow be approximated?
100 - Age = Cellularity (%)
232
What regulates neutrophil maturation?
Granulocyte-colony stimulating factor
233
What regulates the growth and development of megakaryocytes?
Thrombopoietin
234
What are the peripheral (Secondary) lymphoid tissues?
```
Lymph nodes
Spleen
Tonsils (Waldeyer's ring)
Epitheliolymphoid tissues
Bone marrow
```
235
How much does a spleen usually weigh?
150-200g
236
What are the dimensions of a normal spleen
12x7x3cm
237
What does the visceral aspect of the spleen touch?
Left kidney
Gastric fundus
Tail of pancreas
Splenic flexure of colon
238
What does the red pulp of the spleen contain?
Sinusoids
| Cords
239
What is the structure of splenic sinusoids?
Fenestrated
Lined by endothelial cells
Supported by hoops of reticulin
240
What do the cords in splenic red pulp contain?
Macrophages
Some fibroblasts
Cells in transit
241
What arteries does the splenic artery give off?
Trabecular arteries
242
What do the branches of the splenic artery become when they reach the white pulp? What do they give off to the perilymphoid sinuses?
Central arteries:
| - Give off radial arteries
243
What happens to the central arteries when they branch off to the red pulp?
Penicillary arteries
244
How does blood drain from the spleen into the splenic vein?
Trabecular veins
245
What does the white pulp comprise?
Periarteriolar lymphoid sheath:
| - CD4+ cells
246
What forms the malpighian corpuscles?
Periarteriolar lymphoid sheath
| Lymphoid follicles
247
How does splenic enlargement present?
Dragging sensation in LUQ
Discomfort with eating
Pain (if infarction)
248
What is hypersplenism a triad of?
Splenomegaly
Fall in >=1 cellular components of blood
Correction of cytopaenias by splenectomy
249
What is the most common cause of hyposplenism?
Splenectomy
250
What conditions can cause hyposplenism?
Coeliac disease
Sickle cell disease
Sarcoidosis
Iatrogenic
251
What causes the features of hyposplenism?
Reduced red pulp function
252
What does a blood film show in hyposplenism?
Howell-Jolly bodies:
- Basophilic nuclear remnants in RBCs
Other RBC abnormalities
