haematology Flashcards
What is the pathology of myeloma, vs plasmacytoma
What are the complications
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
What is the diagnostic criteria for MGUS vs asx myeloma vs sx myeloma
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
How is myeloma staged
I - III
I - b2-microglobulin <3.5 and albumin >35
II - neither I nor III
III - b2-microglobulin >5.5
What is the first line treatment for myeloma
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
What are the side effects of thalidomide
Somnolence, neuropathy, constipation, teratogenic risk
What is the diagnostic criteria for a plasmacytoma
What is the progression rate from plasmacytoma to myeloma
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
What are the investigations for myeloma / plasmacytoma
MRI whole body or PET
MRI whole spine
What is the management of a bone plasmacytoma
Radical RT - 45Gy/25#, but high rate of progression to MM
surgery - usually if structural instability of bone
What is the RT regimen for a bone plasmacytoma
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
Where is the commonest site for an extra medullary plasmacytoma
How are they treated
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
What are the two types of Hodgkin lymphoma
What are the markers for these
What cell marker is indicative of HL
Classical - 95% - CD15 & CD30+, CD20 & CD45-
Nodular lymphocyte predominant - 5% - CD15 & CD30-, CD20 & CD45+
Reed-Sternberg cells
How does HL present
How is it investigated
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
How is Hodgkin lymphoma staged
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
What is the management of an early stage nodular lymphocyte predominant HL?
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#
What is the management of an advanced stage nodular lymphocyte predominant HL?
Stage 3 - 4: 6x R-ABVD, or R-CHOP
How is the management of classical HL divided
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
What is the management of an early HL (stage 1-2A) with favourable criteria
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
What is the management of an early HL (stage 1-2A) with unfavourable criteria (BEEN)
4x ABVD followed by 30Gy/10# ISRT
or 6x ABVD only
What are the components of ABVD chemotherapy
Doxorubicin, bleomycin, vinblastine, dacarbazine
What is the management of an advanced HL (stage 2B and above)
3x ABVD chemotherapy, then PET
If negative, give further 4x AVD only
If positive, 4x escalated BEACOPP +/- RT
What are the volumes for involved site radiotherapy
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
What breast screening is done after RT for Hodgkins lymphoma
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
What translocation is associated with an anaplastic large-cell lymphoma
t (2;5) - Anaplastic large-cell lymphoma
What translocation is associated with Burkitts lymphoma & what oncogene
t (8;14) or t (2:8) - Burkitt’s lymphoma - C-myc
What translocation is associated withDLBCL & what oncogene
t (3,14) - DLBCL - BCL6
What translocation is associated with Mantle cell lymphoma & what oncogene
t (11;14) - Mantle cell lymphoma - cyclin D1
What translocation is associated with MALT lymphoma
t (11;18) - MALT lymphoma
What translocation is associated with follicular lymphoma & what oncogene
t (14;18) - Follicular lymphoma - BCL2 (in 80-90%)
What translocation is associated with CML
t (9:22) - CML- Abl - massive splenomegaly
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
When is PET indicated in lymphoma staging
DLBCL, follicular and Burkitts
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
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
What is the management of a stage 1A DLBCL
R-CHOP x3 + ISRT 30Gy/15#
or R-CHOP x6
What is the management of a stage 1B-4 DLBCL, with max 1 extranodal site
R-CHOP x6
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
What is the management of bulky DLBCL
R-CHOP x6 + ISRT 30Gy/15#
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
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)
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
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
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)
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
How is a primary mediastinal B cell lymphoma treated
6x R-CHOP + 30Gy/15# to primary
How is a Burkett’s lymphoma treated
Rituximab-based chemotherapy with CNS prophylaxis
High relapse rate
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
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
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
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
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
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
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
How is a gastric marginal B cell lymphoma (MALT) treated, after failure of H. pylori eradication or extra-nodal elsewhere
RT - 24Gy/12#
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
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
How is a conjunctival lymphoma treated
RT - 24Gy in 12#
CTV - Whole conjunctiva
Typically with low energy electrons and bolus
How can RT be used to treat Waldenstroms macroglobulinaemia
TBI before stem cell transplant
14.4Gy/8#, treating twice a day
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
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
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#
When is R-CHOP-14 used
Primary mediastinal B cell lymphoma
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
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
