Lymphoma Flashcards
Compare the px for high grade B and T cell lymphomas
When treated with CHOP‐based protocols, dogs with high‐grade T cell lymphoma (TCL) have a lower remission rate, and those that do achieve a remission are reported to relapse more quickly and survive a shorter time than dogs with comparable stage high‐grade, B cell lymphoma (BCL)
However, the prognosis for dogs with a separate entity of indolent TCL is mostly considerably better than for dogs with any other type of lymphoma
How can you identify T cell lineage
CD3
PARR
Some neoplastic T cells lose the CD3 antigen but retain the TCR, hence some TCL may be negative for CD3 but positive on PARR
Are most lymphomas B or T cell in dogs?
Mostly B cell, although certain breeds are more commonly T cell (e.g. Sharpei, CKCS)
Which type of lymphoma in dogs is more likely to cause hypercalcaemia
Dogs with TCL appear more likely to present with hypercalcaemia, which appears to be mediated primarily by upregulation of parathyroid hormone related protein (PTHrP
What are the major types of t cell lymphoma?
T zone lymphoma (TZL) and high‐grade TCL
What is T zone lymphoma?
characterised by an expanding paracortical population of T cells that compress the germinal centres causing atrophy throughout the medulla. Morphology of the neoplastic cells is small to intermediate with absent to rare mitoses
difficult diagnosis to make on cytology, as the histological characteristics are more important than cell size
When do you treat T zone lymphoma?
Often don’t need to start straight away
There is no consensus as to criteria to use to institute therapy in dogs with TZL. The presence of the following are suggested as reasons to start therapy:
▪ Clinical signs (substage b);
▪ Rapid progression (doubling time of <6 months);
▪ Circulating lymphocyte count >9.2;
▪ Bulky multiple sites >3 cm or one site >7 cm;
▪ Development of myelosuppression due to myelophthisis; or
▪ Organ dysfunction due to infiltration
What are some suggested aetiologies of lymphoma?
Genetic and epigenetic changes and congenital
aberrations
Possible infectious causes unproven as yet in dogs
Environmental factors
Chemical exposure, polluted sites, incinerators and
radioactive waste
Immune system alterations
Many cases have recent inflammatory event
Prior immune mediated disease associated with a
higher risk of subsequent lymphoma
What are the main presentations of lymphoma?
Multicentric 80% Increasingly being subclassified Craniomediastinal 5% Gastro-intestinal 5 – 7% Cutaneous Extra-nodal forms
How does multicentric lymphoma present?
Usually aggressive disease Occasional indolent cases Typical presentation Well dog to mild lethargy, weight loss, inappetance, pyrexia Rapid progression Ocular changes common Big lymph nodes Around 20% pu/pd due to hypercalcaemia
How does cranio-mediastinal lymphoma present?
Can occur as solitary lesion or part of multicentric form
Malaise
Often pu/pd due to hypercalcaemia
Possibly tachypnoea, dyspnoea
Occasionally pre-caval syndrome
Altered position of PMI for cardiac auscultation
How does the gastrointestinal form present?
Tends to be aggressive in dogs
Diagnosis often delayed due to investigation in to GI signs
There may be progression from other GI disease
Clinical signs
Weight loss, anorexia, pan-hypoproteinaemia, evidence of malabsorption
Abdominal masses
Occasionally multicentric lymphadenopathy
How does cutaneous lymphoma present?
Epitheliotrophic and non-epitheliotrophic forms
Epitheliotrophic T cell solitary or generalised may have lesions elsewhere GI tract and local lymph nodes
Non-epitheliotrophic
More frequently B cell
More likely to have lesions elsewhere
What extranodal forms are there?
Hepatosplenic - Aggressive, no peripheral lymphadenopathy T cell Intravascular Ocular signs CNS Bone marrow Renal Rectal lymphoma
What paraneoplastic forms are common with lymphoma?
Hypercalcaemia T cell Immune mediated diseases IMHA IMTP and Pemphigus IMHA, IMTP and Pemphigus foliaceous Monoclonal gammopathies Neuropathies Cachexia
What are the ddx for multicentric lymphoma
Neoplasia - Multicentric lymphoma - Other haematopoetic disease Reactive - Viral, bacteria, fungi, parasites - Check travel history - Leishmania, Ehrlichia sp. Etc. - Immune mediated diseases
What may you see on blood work with lymphoma?
Haematology IMTP: 30 – 50% Neutrophilia: 25 – 40 % Lymphocytosis: 20% Flow cytometry helpful Important to differentiate between leukaemia and stage V lymphoma Biochemistry Hypercalcaemia Check for signs of organ dysfunction
What diagnostic tests are available for testing for lymphoma?
Cytology - Not from areas where reactive changes are likely Immunocytochemistry Histopathology Immunophenotyping Special techniques Immunohistochemistry Flow cytometry PARR
What staging can be done for lymphoma?
Always
CBC and biochemistry and urinalysis
Thoracic radiograph
Often
Abd l l d Abdominal ultrasound
(Immunophenotyping)
Occasionally
Bone marrow aspirate (if Cytopaenias)
Flow cytometry (if Lymphocytosis and/or atypia)
What are the main prognostic factors for lymphoma?
Strong
Substage, immunophenotype, steroid pretreatment, craniomediastinal lymphadenopathy, anatomic location, ongoing response to treatment
Modest
Stage, histopathologic grading, hypercalcaemia, gender, proliferation indices, history of chronic inflammatory disease, low cobalamin
Debatable
circulating enzymes (TK, LDH)
New / Experimental
Ability to detect minimal residual disease after starting treatment
What are extra considerations for treating GI lymphoma?
Significance of intestinal masses
Pre-chemotherapy surgery ?
Possibility of wound healing issues after surgery
Perforation after successful initial treatment
If more diffuse involvement
Translocation also a risk
Perforation still possible
What is the ox when chemotherapy is not initiated?
No treatment
MST 4 – 6 weeks
Prednisolone alone
OOR 30% Median response duration 1 – 2 months
Outline high dose COP
Vincristine, pred, cyclophosphamide
Preferred to low dose COP
Well tolerated protocol
Easily and safely administered in general practice setting
Haematology performed prior to each treatment
Urine sample prior to and post each cyclophosphamide
Consider dose reductions at the start of treatment
Overall response rate 60 % – 80 %
Median survival around 6 – 9 months.
Outline discontinuous CHOP
COP + doxorubicin
Response rate 90 – 95%
Median survival time 10 – 12 months
No advantage to continuous treatment
Outline local treatments with lymphoma
Rarely indicated especially as sole treatments
Radiation might be useful for:
Stage I disease
Palliation of local disease
Half body radiation after inducing remission with
chemotherapy
Lurie et al 2009, JVIM
Surgery
Could be considered for rare Hodgkin’s lymphoma and possibly extranodal and early stage I disease
What are the considerations with CNS lymphoma
Many drugs don’t penetrate the blood brain barrier Cytarabine CCNU Steroids l’asparaginase
Why is complete remission so important?
Increases time to relapse
Increases survival time
Being in CR at the end of a discontinuous protocol leads to a very high chance of regaining remission later using the same protocol.
If CR is not achieved this suggests a resistant
population of tumour cells. These will rapidly
become the dominant population.
What may cause resistance?
Genetic resistance
Increase in MDR-1 pGp activity
P-Glycoprotein pumps include steroids, vinka alkaloids and anthracyclines amongst their substrates
Other mutations
Tumour cells in a protected site
Inadequate dose intensity
If relapse occurs in the low intensity part of the protocol then going back to induction phase might help
Outline rescue protocols
Law of diminishing returns with each rescue
DMAC
72% ORR, 44% CR, 28% PR
Median remission duration 2 mths, 3.5 mths if CR achieved
CCNU, l’asparaginase and prednisolone
87% ORR, 52% CR
Median time to tumour progression 63 days
Single agent anthracyclines if not already used
BUT unlikely to be beneficial if MDR-1 actvity is high.
Outline tx follow up
Restaging
When there are no sentinel lymph nodes to follow
When patient not doing as well as expected or all clinical signs do not resolve
At the end of the induction phase?
At the end of a discontinuous protocol
Follow up for CR patients not on treatment
Monthly
Almost all canine lymphoma patients relapse eventually
Outline treatment for epitheliotropic lymphoma
Typical protocols are COP or CCNU + P
No proven extension of life span
May improve QoL
Response to treatment can be hard to gauge due to natural behaviour of disease
Retinoids have also been used with moderate success for controlling clinical signs
Radiation therapy is very useful for localised mucocutaneous disease
