Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Haematology > Lymphoid Haematological malignancy > Flashcards

Lymphoid Haematological malignancy Flashcards

1
Q

What is one of the main difference between lymphomas and leukemia?

A

Lymphoma tends to arise in the nodal tissue and peripheries
Leukemia arises in the bone marrow and spills out into the peripheral blood

There is significant overlap between the diseases

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

What are the three types of lymphoproliferative disorders?

A

Leukemia
Lymphoma
Multiple myeloma (derived from terminally diferentiated B cell - plasma cell)

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

Des scribe the basic anatomy / structure of a lymph node? where do B and T cells develop in the node?

A

Afferent and efferent lymph limbs
Also have arterial and venous limb for blood supply
From the periphery inwards, there is the capsule, then the surrounding marginal sinus, the the follicles, then the para cortical zone, then the medulla sinus flowing into teh efferent limb

Primary follicles develop into secondary folicles which contain germinal centers

B cell mature in the germinal follicles
T cells mature in the paracortical area

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

Where does B cell maturation happen?

A

Germinal follicles of the peripheral LNs

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

Where does T cell maturation primarily occur?

A

Thymus, then further maturation in the peripheries (LN and other organs)

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

Lymphoma RF?

A

Immune suppression
- medications (MTX, AZA etc)
- Organ or bone marrow transplant
- HIV infection

Exposure to toxins:
- primor chemo
- agent orange herbicide
- Nuclear radiation

Infection
- H pylori, HCV, HIV, HTLV

Autoimmune conditions

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

How is lymphoma most broadly classified?

A

Hodkins and non-hodkins lymphoma

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

How is non hodkins lymphoma most broadly subdivided?

A

T cell NHL
B cell NHL

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

What is the most common form of lymphoma? what is the second and third most common? (options: T cell, B cell, Hodgkins)

A
  • B cell NHL are most common, approx 80%
  • HL is second most common
  • T cell NHL is third most common (much more common in asians)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How is B cell NHL most broadly subdivided? Why is it useful to categorize in this way?

A

Very aggressive, Aggressive, and Indolent

For example:
- Burkits NHL is very aggressive
- DLBC NHL is aggressive
- Follicular NHL is indolent

Useful because agressive ones require Rx, indolent one may be able to be observed

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

What is the most common B cell NHL?

A

DLBC NHL is most common, then follicular NHL

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

Which form of lymphoma is curable, and which is not?

A

Contrary to what you might expect, indolent lymphomas are not curable, aggressive lyumphomas often are
- Indolent: follicular, CLL, MZL
- aggressive: DLBC NHL
- very aggressive: Burkits NHL

Hodkins lymphoma is often curable

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

How does lyumphoma present?

A

Can present with symptoms:
- Weight loss
- fever
- drenching night sweats
- noticed a lump in axilla or neck etc

Can present as incidental examination finding by doctor (ie noticed a lump in neck)

Can be incidental finding on imaging or bloods

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

Which form of Lymphoma is H pylori related to?

A

MALT lymphoma of the stomach
- MALT = mucosa-assisted lymphoid tissue

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

Which part of the gut does mantle cell lymphoma have a predilection for?

A

Colon

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

In which part of the gut can folicular B cell NHL arrise?

A

Duodenum

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

Which form of lymphoma particularly can affect the skin? and what are some examples?

A

T cell lymphomas

Examples:
- Mycoses fungoides - a form of primary cutaneous T cell NHL
- Anaplasic Large cell lymphoma

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

How is lymphoma diagnosed? What type of Bx is preferred?

A

Biopsy (tissue, hone marrow, blood, other)
Clinical features

Core or excicional Bx is preferred, dont get FNA

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

How is Bx tissue used to establish Dx of lymphoma? (ie what are the broad aspects of Bx processing / analysis)

A

Morphology (histology)
Immunohistochemistry / flow cytometry
Genetic profile
- FISH, PCR, cytogenetics

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

What cell surface markers are almost always expressed on Hodkins lympohoma (can also be expressed on other types)?

A

CD30, CD15

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

What is Ki-67 in lymphoma?

A

The Ki-67 is teh proliferation index, gives a measure of how fast the lymphoma is replicating

ie buirkits has a Ki-67 of almost 100% (very fast replicating)

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

How is Bx immunohistochedmistry used in establishing Dx of lymphoma?

A

Immunohistochemistry
- used to determine subtype of lymphoma ie B cell T cell, hodkins
- Used to determine proliferation index Ki-67
- used to determine cell of origin in DLBC NHL (determines subtype of DLBL NHL)
- to identify prognostic markers such as myc, blc2…

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

How is lymphoma staged? explain the different stages?

A

Staged with the ann arbor staging system
from stage 1 - 4

Stage 1 - localized disease. single LN or organ affected

Stage 2 - 2 or more LN regions on teh same side of teh diaphragm

stage 3 - two or more LN regions above and below the diaphragm

stage 4 - Widespread disease (extranodal tissue) affecting multiple organs with or without LN involvement

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

What are some examples of low grade/ indolent lymphoma? (give 4 most common ones)

A
  • Follicular (most common by far)
  • Marginal zone Lymphoma
  • CLL/SLL
  • Lymphoplasmocytic lymphoma (waldenstroms macroglobulinaemia)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Who gets follicular NHL? (demographic features)

A

Older adults (median 60yrs)
Less common in asia and developing countries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Can follicular b cell NHL progress / transform? what does it transform into

A

Yes
Transformation to higher grade DLBC lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are 2 characteristic cell surface markers of follicular B cell NHL?

What is the characteristic translocation leading to up regulation of one of these surface markers?

A

CD10, BCL2

t(14:18)m leads to up regulation of BCL2 which is an antiapototic protein (pro survival)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

How is follicular B cell NHL treated?

A

Usually watch and wait approach, prognosis is good (approx 20 years), however may need to treat advanced disease / symptomatic disease

Stage I/II disease:
- Targeted local radio + R-CVP (rituximab, cyclophosphamide, vincristine, prednisolone)
- Observation

Stage III / IV disease:
- Asymptomatic or low tumour burden can be observed
- Symptomatic / high tumor burden is treated with immuno-chemotherapy +/- maintainance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are some common immuno-chemotherapy regimes used for treatment fo follicular B cell NHL?

A

Immunotherapy agent combined with chemotherapy “backbone” regime

Immunotherapy agent:
- Rituxumab OR obinutuizumab (CD20)

Chemo regime:
- CVP (cyclophosphamide, vincristine, prednisone)
- CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone)
- Bendamustine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are the three types of MZL?

A

extra nodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT)

Nodal MZL (rare)

Splenic MZL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is MZL commonly associated with?

A

Chronic inflamatory diseases (autoimmune or chronic infections) such as:
- H pylori infection in stomatch
- Sjogrens syndrome
- Hashimotos thyroiditis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Gastric MALT is sometimes associated with specific translocation. What is this translocation and why is it relevant?

A

t(11:18) BIRC3/MALT1 translocation
- confers worse prognosis (more difficult to treat)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What type of paraprotein is usually associated with lymphoplasmocytic lymphoma? what is the epponomous name for this?

A

usually IgM paraprotein (Waldenstroms macroglobulinaemia)
- can also have IgG/IgA parprotein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What precursor condition can develop into LPL?

A

IgM MGUS can develop into LPL (approx 10%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Can pts with LPL transformation of IgM MGUS ever get MM?

A

No, MGUS that has transformed into LPL will not develop into MM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What are 2 mutation associated with LPL?

A

MYD88 (very specific for LPL, >90% LPL will have this)

CXCR4 mutation confers worse prognosis (approx 30% have it)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are some symptoms fo very high levels of IgM paraprotein in LPL?

A

this is known as hyperviscopsity syndrome
Sx include visual blurring, headache, retinal changes

this is an indication to treat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

How is LPL treated?

A

Often no treatement required (very indolent progression)

If treatment required:
- Rituxumab-chemo regimes
- BTKi (zanubrutinib) for relapsed disease or pts unfit forR-chemo)

39
Q

What is a side effect of initial treatment of LPL with rituxumab to be aware of?

A

Rituxumab can cause an initial increase in IgM, so need to be cautious if pre-existing high levels of IgM

40
Q

How is LPL treatment monitored?

A

Serial IgM measurements

41
Q

Where does Mantle cell Lymphoma sit in relation to agressive / very agressive lymphomas and indolent lymphomas?

A

Mantle cell lymphoma is not indolent and it is not aggressive / very aggressive
It is considered an intermediate lymphoma

42
Q

What is the characteristic translocation of mantle cell lymphoma? What is the result of this translocation?

A

t(11:14), in >95%
Resulting in over-expression of cyclin D1

43
Q

How is mantle cell lymphoma treated?

A

There are some situation in which observation can be initially used, however low threshold to move to treatment (relative to indolent NHLs for example)

Treatrement for <65yrs:
- Intensive immunochemotherapy (cytarabine containing regimes)
- Upfront autologous SCT following immunochemotherapy (doesnt cure, just increase survival)
- ritux maintainance

Treatment for >65yrs:
- Less intense immunochemotherapy (R-Bendamustine, R-BAC)
- Ritux maintainance

44
Q

Who gets DLBC lymphoma?

A

Median age 60-70s
Higher incidence in developing countries

45
Q

Is there any role for observation in DLBC lymphoma?

A

No, it is an aggressive lymphoma that will always progress if not treated

46
Q

How is DLBC NHL classified into risk groups?

A

International prognostic index (IPI) is used to classify into low risk, low intermediate, intermediate high, high risk groups

  • IPI 0 - 1 is low risk
  • IPI 2 is low intermidate
  • IPIN 3 is intermidate high
  • IPI 4 -5 is high
47
Q

What are some poor prognostic factors in DLBC NHL?

A

Clinical prognostic factors
- High IPI
- Advanced stage
- Bulky tumor (>7.5cm)

Tumor prognostic factors:
- Molecular subtype (germinal centre DLBC NHL, or activated B cell subtypes)
- Dual expression of MYC and BCL2

48
Q

What proteins are expressed in double and triple hit DLBC NHL?

A

Double hit - BCL2, MYC
Triple hit - BCL2, MYC, BCL6

These are both known as high grade DLBL NHL

49
Q

Explain the concept of cell of origin in DLBC lymphoma?

A

DLBC NLH can arise from B cells at different stages of development. for example it can arrive from a germinal B cell (called Germinal center B cell DLBC Lymphoma) or can arse from an activated B cell (called activated B Cell lymphoma)

the cell of origin is determined by immunohistochem looking at cell surface markers

50
Q

What is the mainstay of treatment for DLBC lymphoma?

A

R-CHOP (rituixumab, cyclophosphamide, doxorubicin, vincristine, prednisone)

More intensive chemo regimes are used in high grade DLBC lymphoma

51
Q

What is the treatment for hypersensitivity syndrome?

A

Plasmaphoresis to filter out the paraproteins

52
Q

What is the malignant cell in HL called?

A

Reid sternburg cell (owl eye cells)

53
Q

Why is interpretation of tissue Bx in HL fraught?

A

Because the reid sturnburg cell is often in the minority with numerous reactive normal cells present. Therefore can get sampling error

54
Q

What are the common cell markers on reed sternburg cells?

A

CD 15, CD30

55
Q

Who gets HL?

A

Bimodal age distribution - 30s and older adults
2:1 male predominance

56
Q

How does HL classically present?

A

Non tender rubbery lymphadenopathy most often in cervical LN, but also axilia, and mediastinum
Alcohol intolerance (pain when drink alcohol)

Constitutional Sx commonly associated

57
Q

What are the classifications of HL and how are pts classified into these groups?

A

Early stage, favourable
Earlky stage unfavourable
Advannce

Classified using combination of ann arbor staging (early or advanced stage), and risk factors (favourable, unfavourable)

58
Q

How is HL treated?

A

Trteated with chemoitherapy regimes
Treatment depends on the stage

ABVD (adramycin AKA doxorubacin, bleomycin, vioncristine, dacarbazine)
- Used in early stage disease, or advanced stage disease in the more elderly pts

Escalated BEACOPP (bleomycin, etoposide, Adramycin AKA DOXOrubicin, CYCLOPHOSPHamide, vinCRISTine, procarbazine, prednisolone)
- more intense regime used in advanced stage in young pts
- better cure rate but more side effects such as INFERTILITY

59
Q

ABVD and BEACOPP include Bleomycin. What is a main side effect of bleomycin?

A

Lung toxicity

60
Q

What is a main side effect / toxicity of doxorubicin?

A

Cardiovascular toxicity

61
Q

What are some common blood film findings in CLL?

A

Many small mature lymphocytes in peripheral blood. Smudge cell on film

62
Q

Who gets CLL?

A

Disease of the elderly (70-80yrs)

63
Q

How do pts commonly present with CLL?

A

Most often an incidental findings on bloods (very high WCC)
- 60% asymptomatic at Dx

If symptomatic, common symptoms include lymphadenopathy, fatigue, autoimmune cytopenia’s (AIHA, ITP)

64
Q

What is the precursor lesion to CLL?

A

Monoclonal B lymphocytosis
- monoclonal population of B lymphocytes <5000 cells/microL (<5 x 109/L) in peripheral blood for ≥3 months, without other features of a B cell lymphoproliferative disorder

Approx 1% MBL progress to CLL per year

65
Q

What is the nodal counterpart of CLL?

A

small lymphocytic lymphoma

66
Q

Poor prognostic markers in CLL?

A

High LDH
High Beta 2 microglobulin
Chromosomal abnormalities
TP53 inactivated and unmutated IgVh
- CLL cells that have not entered the germinal center and havent undergone hypermutation of their IgVh have a poorer prognosis than those that have

This is similar to the cell of origin concept of DLBC NHL (ie prognosis of the disease depends on at which point it develops in the normal cells process of maturation)

67
Q

Describe the disease course and progressive sequelae of CLL?

A

Usually a slow progressive disease of the elderly
- slow rising lymphocytosis
- increasing lymphadenopathy and splenomagly
- progressive BM failure
- Progressive immunparesis and B cell immune suppression
- Autoimmune complications such as AIHA, ITP
- secondary skin cancers

68
Q

When should CLL be treated?

A

When it becomes symptomatic
- usually due to worsening anaemia or thrombocytopenia
- AIHA or ITP
- Symptomatic extra nodal involvment
- Constitutional Sx

Treatment may be indicated with progressive lymphocytosis, or lymphocyte doubling time of <6 months

69
Q

How is CLL treated?

A

All pts:
- Ibrutinib/zanubrutinib (BTKi) + venetoclax (BCL2 inhibitor) + Obinutuzumab is first line treatment for all age groups

Chemo used to be first line until Sept 2023

70
Q

What is multiple myeloma?

A

It is a malignancy of plasma B cells which accumulate and destroy bone and bone marrow

71
Q

Why is infection risk increased in multiple myeloma if it is a disease of too much immunoglobulin poroduction?

A

Normal B cell populations produce polyclonal immunoglobulin which provided broad protection against infections

Multiple myeloma malignant plasma cells lead to monoclonal immunoglobulin production (paraprotein), or elevated serum free light chains which leads to a reduction in polyclonal immunoglobulins and therefore increased risk of infection

72
Q

What feature on an electrophretogram is concerning for MM?

A

an M spike
- caused by M protein (AKA paraproteins)

The M spike given the Electrophoretogram and double spike appearance, whereas the normal appearance is that of a single initial spike (due to albumin in the blood) followed by lots of smaller spikes that represent the various other poly clonal immunoglobulins and proteins in the blood

73
Q

What is the difference between light chains and para proteins in MM?

A

paraptoteins is another name for the abnormal monoclonal immunoglobulin that is produced by some myelomas

However some myeloms just produce light chains (either kappa, or lambda light chains) rather than a whole immunoglobulin molecule (which is comprised of 2x heavy chains, and 2x light chains)

74
Q

Approximately what percentage of MM is free light chain only? (ie not paraproteins)

A

15%

75
Q

What are the CRAB features of MM?

A

hyperCalcaemia
Renal failure
Anaemia
Boney leision / osteoporosis

Boney lesions, anaermia, hypogammaglobulinaemia / iunfection, and hypercalcaemia are caused by too many plasma cells

renal failure, hypoerviscosity and neuropathy are caused by too much protein or light chains

76
Q

Myeloma exists on a spectrum of disease. What are the other diseases on this spectrum? (there are three in total)

A

MGUS

Asymptomatic myeloma (used to be called smoldering myeloma

Symptomatic myeloma (used to be called multiple myeloma)

77
Q

What is the definition of MGUS?

A

M protein <30g/L, clonal plasma cells in BM <10%, nil myeloma defining events

78
Q

What is the definition of asymptomatic myeloma? (used to be called smoldering myeloma)

A

M protein >30g/L in blood or >500mg/24hrs in urine
Clonal plsama cell 10-60% in BM
Nil myeloma defining events

79
Q

hat is the definition of symptomatic myeloma? (used to be called multiple myeloma)

A
  • Clonal plasma cells >10% in BM AND a myeloma defining event

> /=1 CRAB feature

> /= 1 biomarker of malignancy
- Clonal plasma cells >60% in BM
- Serum FLC ratio >100
- > 1 focal MRI leision >5mm

80
Q

How does myeloma typically present?

A

Bone pain
Low BMD / OP with paraprotein
Pathological fractures
Anaemia with high total protein
Acute renal failure and anaemia with high total protein
Back pain and anaemia (bone pain)
Hyperviscosity syndrome

81
Q

How can renal function be affected in myeloma?

A

Myeloma cast nephropathy
Light chain deposition disease
AL amyloidosis
Aquired fanconi syndrome
Hypercalcaemia, hyperuricaemia

82
Q

Features of MM on blood film?

A

Rouleaux cells
Occasional circulating plasma cell

83
Q

Bone marrow findings in MM?

A

Plasma cells, often with atypical features

84
Q

Broadly speaking, how is symptomatic myeloma treated?

A

Treatment regime depends on whether the pt is SCT eligible (ie <60 and fit)

Transplant eligible patients
- induction
- Transplant
- Maintenance
- Treatment of relapsed disease

Transplant ineligible patients:
- Induction
- Maintenance
- treatment of relapsed disease

85
Q

What regime is used for induction in both SCT eligible and ineligible pts with symptomatic myeloma?

What regime is used for maintainance therapy in symptomatic myeloma?

A

Induction
Bortezomib (proteasome inh) + lenolidomide + dexamethazone

Maintenance
- SCT eligible - Lenolidomide ongoing
- SCT ineligible - lenolidomide + dexamethazone

86
Q

What are some aspects of supportive care in MM?

A

Treatment of Osteoporosis / bony lesions
- Bisphosphonates

Treatment of hypogamaglobulinaemia
- IVIg

Treatment of anaemia
- PRBC tranfusions PRN

Management of steroid side effects

Management of Bortexomib side effects
- Neurpathy
- VZV prophylaxis

87
Q

How are Chimeric Antigen receptor T cell made (CAR T cells)?

A

T cells are collected from teh pt via venepuncture

A modified virus is used to transfer DNA into the pts T cells so they will produce the desired chimeric antigen receptor
- the CAR has 2 ends: a binding site specific to the tumour cell, and a signalling end that activateds the T cell to kill the tumour cell

Once the desired CAR T cell is made it is grown in the lab (millions of copies)

The expanded population of CAT T cells is infused into the pt

88
Q

What are some toxicities of CAR T cells?

A
  • Cytokine release syndrome (CRS)
  • Immune effector cell associated neurotoxicity syndrome (ICANS)
  • Infection
    • T cell suppression from leukodepletion prior to CAR T cell infusion
    • B cell aplasia (hypogammaglobulinaemia)
  • Haemophagocytic lymphohistiocytosis/ macrophage activation syndrome (HLH/ MAS
89
Q

Does CRS or ICANS occurs first?

A

CRS is the initial side effect, then ICANS happens

90
Q

What are some symptoms / features of CRS? How is it graded based on symptoms / signs?

A

CRS is a systemic inflammatory condition due to mass release of cytokines following CAR T cell infusion

It is graded 1 - 4 based on presence or absence of fever, hypotension and hypoxia
- Grade 1: fever
- Grade 2: fever + hyupotension (not on supports) + hypoxia (LFNP)
- Grade 3: fever + hypotension (ionotropes but not vassopressin) + hypoxia (HFNP, non re breather)
- Grade 4 - - Grade 3: fever + hypotension (Multiple ionotropes) + hypoxia (NIV, intubation)

91
Q

Treatment of CRS?

A

Stepwise increased in Tocilizumab +/- dexamethasone based on grade

Supportive care (ie ICU) if required

92
Q

What are some symptoms / features of ICANS? How is it graded based on symptoms / signs?

A

It is graded 1 - 4 based on conscious state, seizures, motor findings, Elevated ICP/cerebral oedema

93
Q

How is ICANS managed?

A

Managed based on grade 1-4
- Grade 1: dex 10mg stat
- Grade 2: Dex 10mg QID, consider methyl pred if nil improvment, consider anikinra
- Grade 3: high dose methyl pred, consider anikinra, control seizures
- Grade 4: ICU

Haematology (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions