lymphoproliferative disorders Flashcards

1
Q

what is leukaemia

A

“white blood”

generally used to describe a cancer that you can see in the blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is lymphoma and what can they present w/

A

cancers of lymphoid origin

can present w/ lymphadenopathy or extranodal involvement or w/ bone marrow involvement

systemic (B) symptoms: weight loos (>10% in 6mths), fever, night sweats, pruritus, fatigue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

diagnosing a leukaemia/lymphoma

A

> 70 different types, defined by the malignant cell characteristics

  • biopsy - tells us what type it is (THIS IS HOW THE DIAGNOSIS IS MADE)
  • clinical examination and imaging - tells us where it is (STAGING)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

staging of lymphoma/leukaemia

A

location and extent of the disease

information about prognosis

sometimes influences treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

lymphocyte differentiation

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

when can malignant conditions occur in the process of lymphocyte differentiation

A

bone marrow: earliest stages of lymphoid cell development e.g. acute lymphoblastic leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

classifications of lymphomas

A

Hodgkin lymphoma is a specific disease

Non-Hodgkin lymphoma is everything else (~70 subtypes)
- divided into high and low grade

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

key lymphoproliferative disorders (common to least common)

A

Non-Hodgkin lymphoma
- high grade (diffuse large B cell lymphoma), low grade (follicular, marginal zone)

Chronic lymphocytic leukaemia (CLL) - presents in a similar way to low grade NHL

Hodgkin lymphoma

Acute lymphoblastic leukaemia (ALL)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how common are the different lymphoproliferative disorders

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is ALL

A

cancerous disorder of lymphoid progenitor cells

no differentiation, instead there is rapid and uncontrolled growth and accumulation

usually in bone marrow but they can go anywhere

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

normal lymphoid progenitor cells

A

immature

rapidly proliferating cells that differentiate into lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what condition is this

A

ALL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

how common is ALL

  • incidence
  • age
  • what cell lineage
A

1-2/100 000 pop/yr

75% cases occur in children <6y/o

75-90% cases are of B cell lineage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

how does ALL present

A

2-3wk hx of bone marrow failure or bone/joint pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

typical ALL hx

A

17y/o male
1mth impaired vision (both eyes)
1/2 stone weight loss
SOB on minimal exertion

fundoscopy: retinal haemorrhages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

blood count for ALL

A

low Hb
high WCC
low plts

bone marrow - 90% B lymphoblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what can be seen here

A

normal bone marrow

white circles = fat

normal mix of different types of blood cells and platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what can be seen here

A

abnormal bone marrow

hypercellular and uniform cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

ALL cells characteristics

A

large cells

express CD19
CD34, TDT

haven’t had the chance to develop and mature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what is CD19

A

marker expressed by all B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what do CD34 and TDT indicate

A

markers of very early immature cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

treatment for ALL

A

induction chemotherapy to obtain remission
consolidation therapy
CNS directed treatment
maintenance treatment for 18mths

stem cell transplantation - if high risk of relapse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

newer therapies for ALL

A

bi-specific T cell engagers (BiTe molecules)

CAR T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

example of bi-specific T cell engagers

A

blinatumumab

25
how do bi-specific T cell engagers work
binds to tumour cells (CD19) and activates and recruits pts own T cells to attack the leukaemia cells
26
what are CAR T cells
chimeric antigen receptor T cells
27
how are CAR T cells made and used
patient/healthy 3rd party T cells harvested transfected to express a specific T cell receptor expressed on leukaemia cells (CD19) expanded in vitro re-infused into patient can be curative in pts w/ very resistant disease but very expensive
28
key side effects of T cell immunotherapy
cytokine release syndrome neurotoxicity
29
T cell immunotherapy: cytokine release syndrome
fever, hypotension, SOB CAR T cell effect correlated to presence of CRS - sig. number require ITU support
30
T cell immunotherapy: neurotoxicity features
confusion w/ normal conscious level seizure, headache, focal neurology, come
31
ALL poor risk factors
increasing age increased WCC cytogenetics/molecular genetics: t(9;22), t(4;11) slow/poor response to treatment
32
ALL outcome
adults: - complete remission rate ~90% - leukaemia free survival at 5y 30-35% children - 5y overall survival ~90% - poor risk pts (slow response to induction or philadelphia +ve) 5y OS 45%
33
what happens to the cells in CLL
abnormal cells are mature - usually resemble normal, well behaved lymphocytes - grow slowly, or not at all - classic example of a low grade condition - carry many of the normal markers that B lymphocytes have
34
what does a diagnosis of CLL require
lymphocyte count >5 (normal is <4)
35
CLL incidence
``` >1700 new cases p/a UK commonest leukaemia worldwide 2M:1F occasionally familial rare in far east ```
36
CLL presentation
often asymptomatic frequently: - bone marrow failure (anaemia, thrombocytopenia) - lymphadenopathy - splenomegaly (30%) - fever and sweats (<25%) less commonly: - hepatomegaly - infections - weight loss
37
CLL associated findings
immune paresis haemolytic anaemia - 20% have +ve direct antiglobulin test - 8% clinical evidence of haemolytic anaemia
38
what is immune paresis
loss of normal immunoglobulin function
39
how is CLL staged
Binet staging system
40
CLL - Binet staging
A - <3 LN areas, median survival same as age matched controls B - ≥3 LN areas, ~8yrs med survival C - stage B + anaemia/thrombocytopenia, ~6yrs
41
CLL indications for treatment
``` progressive bone marrow failure massive lymphadenopathy progressive splenomegaly lymphocyte doubling time <6mths or >50% increase over 2mths systemic symptoms AI cytopenias ```
42
CLL treatment
often nothing - watch and wait cytotoxic chemotherapy monoclonal antibodies novel agents
43
cytotoxic chemotherapy for CLL
fludarabine | bendamustine
44
monoclonal antibodies for CLL
rituximab | obinatuzumab
45
novel agents for CLL
less immunosuppressive, oral treatments Bruton tyrosine kinase inhibitor e.g. ibrutinib PI3K inhibitor e.g. idelalisib BCL-2 inhibitor e.g. venetoclax
46
CLL poor prognostic markers
``` advanced disease (stage B/C) atypical lymphocyte morphology rapid lymphocyte doubling time (<12mth) CD38+ expression loss/mutation p53, del 11q23 (ATM gene) unmutated IgVH gene status ```
47
presentation of lymphoma
lymphadenopathy/hepatosplenomegaly extranodal disease B symptoms bone marrow invlolvement
48
assessment/staging of lymphoma
LN biopsy CT scan bone marrow aspirate and trephine
49
staging of lymphoma
I: 1 nodal site of involvement II: 2 separate nodal sites, either above or below the diaphragm but not both III: multiple nodal sites, both above and below the diaphragm IV: extranodal disease involvement A: absence of B symptoms B: fever, night sweats, weight loss
50
how is NHL classified
lineage: B or T cell (90% B cell origin) grade: high vs low
51
low grade NHL
indolent, often asymptomatic | responds to chemotherapy but incurable
52
high grade NHL
aggressive, fast growing require combination chemo can be cured
53
specific types of NHL
diffuse large B cell lymphoma: - commonest subtype of lymphoma - high grade follicular lymphoma: - 2nd commonest subtype of lymphoma - low grade - like CLL, watch and wait if not causing problems - both arise from a transformation in the germinal centre of a LN
54
how are diffuse large B cell lymphoma and follicular lymphoma treated
combination chemotherapy: | anti-CD20 monoclonal ab + chemo
55
how common is HL
30% of all lymphomas
56
age of HL | M vs F
bimodal age curve: 15-35y/o 2nd peak later in life 1.9M:1F
57
associations w/ HL
EBV | familial and geographical clustering
58
treatment of HL
``` combination chemo (ABVD - 4 different drugs) +/- radiotherapy monoclonal ab (anti-CD30) - brentuximab immunotherapy (checkpoint inhibitors) ``` PET scanning central to assessment of response to treatment