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haematology Flashcards

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1
Q

What is the pathology of myeloma, vs plasmacytoma

What are the complications

A

Myeloma - Plasma cell neoplasm, secreting monoclonal protein, typically IgG or IgA, and rarely IgD
Plasmacytoma - localised proliferation of plasma cells, either arising from bone or extra medullary

Pathological fractures
Myelosuppression
Hyper-Ca, renal failure, amyloid deposition

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2
Q

What is the diagnostic criteria for MGUS vs asx myeloma vs sx myeloma

A

MGUS - serum M protein <30g/L, plasma cells in bone marrow <10%, asx

Asx myeloma - serum M protein >30g/L, plasma cells in bone marrow ≥10%, asx

Sx myeloma - serum M protein >30g/L, plasma cells in bone marrow ≥10%, sx of CRAB
C - Ca > 2.75
R - renal impairment Cr >173
A - anaemia Hb <10
B - bone lesions or compression fracture

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3
Q

How is myeloma staged

A

I - III

I - b2-microglobulin <3.5 and albumin >35
II - neither I nor III
III - b2-microglobulin >5.5

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4
Q

What is the first line treatment for myeloma

A

If <70 & fit - Velcade (bortezomid)-based ChT (with thalmidomide/dex or cyclophosphamide/dex) & stem cell transplant

If >70 or less fit - weekly chemotherapy (CTDa / MPT (melphalen-pred-thal) / VCD (weekly)

RT for bone disease - pain, impending fracture or post-fracture, MSCC - 8Gy/1# or 20Gy/5

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5
Q

What are the side effects of thalidomide

A

Somnolence, neuropathy, constipation, teratogenic risk

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6
Q

What is the diagnostic criteria for a plasmacytoma

What is the progression rate from plasmacytoma to myeloma

A

histologically confirmed single lesion, commonly vertebrae, ribs, sternum
and with normal bone marrow biopsy (<10% plasma cells)
and serum paraprotein <20g/L
Normal bloods - Ca, Hb, renal function
Normal skeletal survey

50% of bone will progress in 2-4yrs, 30% of soft tissue plasmacytoma

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7
Q

What are the investigations for myeloma / plasmacytoma

A

MRI whole body or PET
MRI whole spine

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8
Q

What is the management of a bone plasmacytoma

A

Radical RT - 45Gy/25#, but high rate of progression to MM
surgery - usually if structural instability of bone

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9
Q

What is the RT regimen for a bone plasmacytoma

A

CTV = whole vertebra, and any soft tissue extension with a 1.5cm margin
CTV-PTV margin - further 0.5-1cm

If adjuvant RT - CTV is whole surgical field

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10
Q

Where is the commonest site for an extra medullary plasmacytoma

How are they treated

A

90% in head and neck

Radical RT - 45Gy/25#
Or surgery, with adjuvant RT if incomplete resection

CTV = GTV +1.5-2cm
CTV-PTV margin 0.5-1cm

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11
Q

What are the two types of Hodgkin lymphoma
What are the markers for these
What cell marker is indicative of HL

A

Classical - 95% - CD15 & CD30+, CD20 & CD45-
Nodular lymphocyte predominant - 5% - CD15 & CD30-, CD20 & CD45+

Reed-Sternberg cells

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12
Q

How does HL present
How is it investigated

A

Painless LN enlargement
B symptoms

Excision biopsy of lymph node
ESR - prognostic
Bloods incl viral hepatitis and HIV, b2-microglobin, LDH, albumin
Staging imaging - CTCAP and PET

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13
Q

How is Hodgkin lymphoma staged

A

Stage 1 - Single LN region or Single Extranodal site (I-E)

Stage 2 - ≥ 2 LN regions on same side of diaphragm
Or Single Extranodal site + regional LNs +/- contiguous LN regions on same side of diaphragm (II-E)

Stage 3 - Nodes both sides of diaphragm (includes spleen as LN)

Stage 4 - Non-contiguous extranodal involvement

E (stage 1&2 only) - extranodal contiguous extension
A - no B symptoms
B - B symptoms

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14
Q

What is the management of an early stage nodular lymphocyte predominant HL?

A

Management according to stage:
1A or 2A with ≤2 sites - RT only, 30Gy/15#

Stage 2A otherwise - 2x ABVD chemotherapy then RT 20Gy/10#

If bulky disease (>10cm) - 4x ABVD followed by RT 30Gy/15#

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15
Q

What is the management of an advanced stage nodular lymphocyte predominant HL?

A

Stage 3 - 4: 6x R-ABVD, or R-CHOP

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16
Q

How is the management of classical HL divided

A

According to stage:
1-2A, split also according to favourable or unfavourable features
2B-4

Where 2B = ≥2LNs sites on same side of diaphragm but with B-symptoms

Unfavourable features for an early HL - BEEN:
- Bulky
- Extranodal areas
- ESR >50
- ≥3 LN areas

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17
Q

What is the management of an early HL (stage 1-2A) with favourable criteria

A

2x ABVD + ISRT 20Gy/10#

or if young and female and axillary/mediastinal mass, to avoid RT (breast irradiation risk):
3x ABVD and pet scan
If PET negative - no further treatment
If PET positive -> 4th ABVD & 30/15

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18
Q

What is the management of an early HL (stage 1-2A) with unfavourable criteria (BEEN)

A

4x ABVD followed by 30Gy/10# ISRT
or 6x ABVD only

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19
Q

What are the components of ABVD chemotherapy

A

Doxorubicin, bleomycin, vinblastine, dacarbazine

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20
Q

What is the management of an advanced HL (stage 2B and above)

A

3x ABVD chemotherapy, then PET
If negative, give further 4x AVD only

If positive, 4x escalated BEACOPP +/- RT

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21
Q

What are the volumes for involved site radiotherapy

A

CTV - define superior and inferior extent of original disease on pre-chemo imaging
Expanded cranio-caudally by 1.5cm and axially to include involved nodal space
Edit off natural barriers to spread: air, muscle, bone

PTV
H&N 0.3 – 0.5cm
Mediastinum - 1cm transversely and 1.5cm cranio-caudally
All other sites 1cm

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22
Q

What breast screening is done after RT for Hodgkins lymphoma

A

Screening offered to all women given mediastinal RT <35 years
Start screening 8 years post RT or by age 30, whichever comes later

Annual MRI if <30 years/dense breasts

Annual mammogram age 30-50
Back to 3 yearly mammogram >50 years

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23
Q

What translocation is associated with an anaplastic large-cell lymphoma

A

t (2;5) - Anaplastic large-cell lymphoma

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24
Q

What translocation is associated with Burkitts lymphoma & what oncogene

A

t (8;14) or t (2:8) - Burkitt’s lymphoma - C-myc

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25
What translocation is associated withDLBCL & what oncogene
t (3,14) - DLBCL - BCL6
26
What translocation is associated with Mantle cell lymphoma & what oncogene
t (11;14) - Mantle cell lymphoma - cyclin D1
27
What translocation is associated with MALT lymphoma
t (11;18) - MALT lymphoma
28
What translocation is associated with follicular lymphoma & what oncogene
t (14;18) - Follicular lymphoma - BCL2 (in 80-90%)
29
What translocation is associated with CML
t (9:22) - CML- Abl - massive splenomegaly
30
What proportion of DLBCL have bone marrow involvement And what genetic change should be tested for, and how
10% MYC rearrangement via FISH If detected -> further testing for BCL2 and BCL6 rearrangements (prognostic markers) If all three positive - poor prognosis
31
When is PET indicated in lymphoma staging
DLBCL, follicular and Burkitts
32
What factors influence the prognosis of DLBCL?
IPI prognostic score ‘APLES’ Age > 60 years PS >2 LDH >1 Extra-nodal site Stage III or IV
33
How is the management of DLBCL categorised
Stage 1A Stage 1b-4, with max 1 extra-nodal site Stage 4 with ≥2 extranodal sites Bulky disease
34
What is the management of a stage 1A DLBCL
R-CHOP x3 + ISRT 30Gy/15# or R-CHOP x6
35
What is the management of a stage 1B-4 DLBCL, with max 1 extranodal site
R-CHOP x6
36
What is the management of a stage 1B-4 DLBCL, with ≥2 extranodal sites
R-CHOP x6 + CNS prophylaxis with intrathecal or high dose methotrexate
37
What is the management of bulky DLBCL
R-CHOP x6 + ISRT 30Gy/15#
38
When is CNS prophylaxis with IT/high dose methotrexate indicated
Testis, Breast, Adrenal gland or Kidney Raised LDH and 2+ Extra nodal sites Or 4 / 5 IPI risk factors: Age>60, PS ≥2, LDH raised, >1 Extranodal site, Stage 3/4
39
When is consolidation RT indicated for DLBCL
Stage 1A-2A disease (if 3x R-CHOP only given) Bulky disease In elderly pts unable to have chemo High risk cases (e.g. testes, breast)
40
How is involved site RT done for DLBCL
GTV planned according to pre-tx volume CTV - GTV grown sup/inf by 1.5cm and axillary to include nodal level *Parotid, Breast, Spleen, Stomach & Liver - CTV is whole organ PTV H&N: + 3-5mm Mediastinum: +1cm transversely & +1.5cm Sup/Inf All other sites: +1cm
41
What forms the majority of primary CNS lymphoma What imaging and investigation is required
90% DLBCL 20% also have intra-ocular component - need ophthalmic assessment Imaging: USS testes, CTCAP - exclude primary MRI head Ix: Bloods incl viral hepatitis & HIV Biopsy LP
42
What is the treatment for primary CNS lymphoma
<60 &fit - 4x matrix chemotherapy and stem cell transplant or WBRT (equivalent outcomes) WBRT dose: Partial response to chemo - 36Gy/20# +/- 9Gy/5# boost to 45Gy/25# Complete response - 23.4Gy/13# >60 or not fit R-MP chemotherapy (ritual, metho, procarbazine)
43
What is the commonest histology for primary testicular lymphoma What is the treatment
80-90% are DLBCL, with propensity for CNS spread 30% rate of relapse within 2yrs Tx: Orchidectomy 6x R-CHOP + CNS prophylaxis with high dose / IT methotrexate RT to contralateral testis - 30Gy/15# - typically treated with 9MeV electrons
44
How is a primary mediastinal B cell lymphoma treated
6x R-CHOP + 30Gy/15# to primary
45
How is a Burkett's lymphoma treated
Rituximab-based chemotherapy with CNS prophylaxis High relapse rate
46
What is the classification of peripheral T-cell lymphoma How are they generally treated
Peripheral Primary cutaneous Leukaemia Tx: R-CHOP followed by stem cell transplant
47
How is an EBV NK/T-cell associated lymphoma treated
If early stage, I-II - treat with early RT Otherwise, neo-adjuvant GELOX chemo, followed by RT and further GELOX chemo RT: 50Gy/25# to GTV +1-2cm
48
What is Sezary syndrome
Sezary syndrome = bone marrow involvement: presence of erythroderma, LN and Sezary cells in peripheral blood Mycosis fungicides with sezary syndrome is the commonest form of cutaneous T-cell lymphoma
49
How is MF/sezary syndrome treated
Observe until symptomatic Skin-directed treatment - topical steroids, psoralen or UV therapy Palliative RT to symptomatic lesions - 8Gy/2# with 0.5-1cm margin, treating to a depth of 7-9mm Total skin electron beam therapy 30Gy/15#, treating 4-5x/week 6MeV with angled fields with shielding of eyes and nails
50
Where may be under-dosed with total skin electron therapy
Areas that may be under-dosed: top of scalp, soles, palms, perineum, infra-mammary areas. These regions may require additional treatment
51
what are the side effects with total skin electron therapy
Acute: erythema, dry desquamation, hair and nail loss, reduced sweating Late: secondary skin cancers, long term skin changes: hyperpigmentation & telangiectasia
52
How is a follicular lymphoma treated
If asx and low tumour burden - observe Stage 1A-2A with contiguous nodes - radical curative ISRT 24Gy/12#, but not many present at this stage >stage 2A - R-CVP or R-CHOP, followed by maintenance rituximab Must re-biopsy recurrence as risk of transformation to high grade DLBCL
53
How is a gastric marginal B cell lymphoma (MALT) treated, after failure of H. pylori eradication or extra-nodal elsewhere
RT - 24Gy/12#
54
What is the treatment for a mantle cell lymphoma
Tend to present disseminated Fit pts - NORDIC regime - R-CHOP + cytarabine, followed by stem cell transplant Less fit pts - R-CHOP followed by maintenance rituximab 2nd line ibrutinib Mantle cell lymphoma is very radiosensitive so RT can be used for local disease or palliation
55
How is an orbital lymphoma treated
Stage 1 - RT only, 30Gy/15# (24Gy/12# if follicular lymphoma) Stage >1 - chemotherapy followed by RT If posterior orbit involved, give intrathecal methotrexate RT given to whole orbit, as wedge pair with corneal shielding - angled back to avoid contralateral lens, or as half beam block
56
How is a conjunctival lymphoma treated
RT - 24Gy in 12# CTV - Whole conjunctiva Typically with low energy electrons and bolus
57
How can RT be used to treat Waldenstroms macroglobulinaemia
TBI before stem cell transplant 14.4Gy/8#, treating twice a day
58
What are the side effects of TBI, and how are they classified
Acute Skin erythema Dry sore throat Fatigue Nausea & decreased appetite Diarrhoea Mucositis and swelling of parotids Acute bone marrow suppression Late Second malignancy Infertility Hypothyroid Pulmonary fibrosis Cataracts
59
What are the adverse prognostic risk factors for NHL (IPI prognostic score)
A - age >60 P - PS >2 L - elevated LDH E - >1 extra nodal site S - stage III or IV
60
What CD markers are positive for a primary mediastinal B cell lymphoma What is the standard of care
CD30 & CD 79A 6x R-CHOP & ISRT 30Gy/15#
61
When is R-CHOP-14 used
Primary mediastinal B cell lymphoma
62
When is R-CHOP-21 used
CD20+ve Diffuse Large B-Cell Non-Hodgkin’s Lymphoma Patients with symptomatic Stage III or IV follicular lymphoma
63
What prognostic score is used for follicular lymphoma What does it consist of
FLIPI score - HALLS H - Hb<12 A - Age >60 L - LDH >ULN L - ≥5 LN sites S - stage 3-4
64

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