Haemopoienic neoplasia 1 & 2 Flashcards
Define lymphoma
diverse group of malignant neoplasms that originate from lymphoreticular cells
Where does lymphoma originate?
LNs, spleen, or LT almost anywhere in the body
How common is canine lymphoma?
one of the commonest malignant tumours in dogs
Signalment - canine lymphoma
- middle aged to aolder (6-9yo) but can be any age
- Boxers, Scottish Terriers, Bassets, Bulldogs, lab retrievers, airedales, st bernards
- familial inicdences (bull mastiffs and rottweilers)
Aetiology - canine lymphoma
- unknown
- genetics (breeds)- chromosomal abnormalities and mutations in tumour suppressor genes (p53) and oncogenes
- environment (herbicides, strong magnetic fields, residence in industrial areas weakly/moderately associated)
Incidence - feline lymphoma
one of commonest malignant tumours in cats
Signalment - feline lymphoma
- median age is 9-11y but can be any age
- previously common in younger cats but FeLV vaccine has changed this
- young siamese and oriental cats (mediastinal lymphoma)
Aetiology - feline lymphoma
- FeLV positive (recombination of FeLV genetic material with host DNA –> oncogenic transformation. Immunosuppression too)
- Vaccination has reduced FeLV positive cases
- FIV positive but unknown mechansim, possibly immunosuppression
- genetics? (siamese and oriental and mediastinal type)
- sites of chronic inflammation (IBD?)
- immunosuppression (cyclosporine post renal-transplant)
- spontaneous
Commonest presentation of canine lymphoma
multicentric lymphoa (80-85% cases in dogs):
- peripheral lymphadenopathy (markedly enlarged LNs, painless, moveable, multiple)
- often asymptmatic
- sometimes vague lethargy, malaise, wt loss, anorexia, pyrexia, PU/PD if hypercalacemic
+/- hepatosplenomegly
Ddx - canine multicentric lymphoma
- disseminated infxn causing lymphadenitis
- I-M dz
- other haematopoetic tumours (leukaemia, myeloma)
- metastatic/ disseminated neplasia of other types (histiocytic sarcoma, MCT)
- generalised skin dz
- sterile granulomatous lymphadenitis
What is the 2nd commonest presentation of canine lymphoma?
GIT lymphoma (approx 7% cases)
CS - canine GIT lymphoma
- COMMON: wt loss, anorexia, vomiting, diarrhoea
- OCC: jaundice if concurrent liver involvement
- localised mass or multifocal/diffuse thick loops of intestine +/- mesenteric LN enlargemetn on exam
Ddx - canine GIT lymphoma
- IBD (esp with diffuse thickening of intestine)
- other GI tumours
- FB
- intussusception
How common is canine mediastinal lymphoma?
3rd commonest case, approx 3% cases
CS - canine mediastinal lymphoma
- cranial mediastinal mass +/- pleural fluid
- dyspnoea
- tachypnoea
- cough
- wt loss
- regurgitation
- heart sounds ventrally
- loss of chest compressibility (cats)
- horner’s
- caval syndrome
What phenotype does canine mediastinal lymphoma tend to be?
often TC type
Do you get hypercalcaemia with mediastinal lymphoma?
yes can do:
- common in dogs, rare in cats
- CS: PD, PU, dehydration, malaise, vomiting, bradycardia, mm tremors, constipation
Ddx - canine mediastinal lymphoma
- other tumurs (thymoma, ectopic thyroid tumour, thymic carcinoma, chemodectoma, metastatic neoplasia)
- non-neoplastic mass lesions: abscess, granulomatous disease, cyst
- other causes of effusion: pyothorax, chylothorax, heart failure, haemothorax
Location - cutaneous lymphoma
solitary or generalised, variable presentation
What are the 2 forms of canine cutaneous lymphoma?
- epitheliotropic form ‘ mycosis fungoides’
- non-epitheliotropic form
Describe the epitheliotropic form of canine cutaneous lymphoma
- TC
- 3 stages: scaling, alopecia, pruritus –> erythematous, thickened, ulcerated, exudative –> proliferative plaques and nodules with progressive ulceration
Describe the non-epitheliotropic form of canine cutaneous lymphoma
- TC or BC
- affects mid to deep dermis, sparing the epidermis
Ddx - canine cutaneous lymphoma
- infectious dermatitis
- I-M dermatitis
- histiocytic skin disease
- other cutaneous neoplasia (MCT or metastatic neoplasia)
What are the extranodal types of lymphoma that occur in dogs?
- hepatic
- splenic
- ocular lymphoma
- renal
- CNS/ spinal
- nasal/ nasopharyngeal, laryngeal/tracheal
Describe canine ocular lymphoma
- seen alone or with generalised disease
- signs of uveitis, blepharospasm, infiltration, haemorrhage, retinal detachment
What is the commonest presentation of feline lymphoma?
GIT (>50% cases)
CS - feline GIT lymphoma
- wt loss
- anorexia
- V and or D
+/- jaundice if concurrent liver involvement
What are the 2 forms of feline GIT lymphoma?
- high grade form
- low grade form
Describe the high grade form of feline GIT lymphoma
- often presents with mass lesions (GI mass/ mesenteric LN)
- relatively short hx of illness
- may have signs of GIT obstruction
- median age 10y
Describe the low grade form of feline GIT lymphoma
- may be diffuse thickening of intestinal loops or mild lymphadenopathy
- may be more chronic hx (months)
- median age 13 y
Ddx - GIT lymphoma
- IBD (especially with diffuse thickening of itnestines)
- other GI tumours
- FB, intussusception
- r/o other dz of elferly cats causing wt loss (hyperthyroidism, renal failure, DM)
What is the 2nd commonest type of feline lymphoma?
Mediastinal lymphoma (10-20% cases)
Describe feline mediastinal lymphoma
- ranial mediastinal mass +/- pleural fluid, other sites may be affected concurrently
- tends to occur in younger cats
- often TC phenotype
- hypercalcaemia is rare in cats vs dogs
Ddz - feline mediastinal lymhoma
- other tumours (thymoma, ectopic thyroid tumour, thymic carcinoma, chemodectoma, metastatic neoplasia)
- non-neoplastic mass lesions: abscess, granulomatous disease, cyst
- other causes of effusion (FIP, pyothorax, chylothorax, heart failure, haemothorax)
What can be a classic sign of feline mediastinal lymphoma?
loss of compressibility of thorax wall
Describe feline nodal lymphoma
- generalised peripheral lymphadenopathy alone unusual in cats (4-10% cases) but up to 25%% cats have enlarged LNs as a component of dz
- in pure nodal forms, single LN/ regional LN enlargement is more common than multiple. An uncommon distinct form exists, called Hodgkin’s-like lymphoma/ TC rich BC lymphoma, which typically involves solitary or regional LNs of head and neck
Ddx - feline nodal lymphoma
AS FOR DOGS:
- disseminated infxn causing lymphadenitis
- I-M dz
- other haematopoetic tumours (leukaemia, myeloma)
- metastatic/ disseminated neplasia of other types (histiocytic sarcoma, MCT)
- generalised skin dz
- sterile granulomatous lymphadenitis
- benign hyperplastic LN syndromes (unique to cat)
Describe feline renal lymphoma
- 5-10% cases
- large irregular kidneys on palpation (often bilateral), signs of kidney dz (PD/PU, anorexia, wt loss)
- median age 9y
- can be concurrent with lymphoma elsewhere (GIT)
- 40-50% tx cats develop CNS lymphoma (unknown why)
- often intermediate-high grade
Ddx - feline renal lymphoma
- polycystic kidney disease
- pyelonephritis
- FIP
- acute renal failure
- hydronephrosis
- perinephric pseudocyst
- other renal tumours (carninoma)
Describe feline hepatic/splenic lymphoma
- 5-10% cases
- CS: malaise, jaundice (if liver involved)
- maybe concurrent with GIT lymphoma /other sites)
Ddx - feline hepatic/ splenic lymphoma
- other splenic masses (feline MCT, HSA)
- other causes of hepatic enlargement/ jaundice (cholangiohepatitis, other neoplasia)
How common is feline nasal/nasopharyngeal lymphoma?
5-10% cases, tends to be older cats
Describe feline nasal/nasopharyngeal lymphoma
75% BC, often localised but can spread to local LNs or pop up elsewhere later on. Often intermediate to high grade
CS - feline nasal/ nasopharyngeal lymphoma
- chronic nasal discharge (serosanguinous to mucopurulent)
- epistaxis
- sneezing
- stertor
- anorexia
- facial deformity
- exophthalmos
- epiphora
Ddx - feline nasal/ nasopharyngeal lymphoma
- cat flu
- other neoplasms (adenocarcinoma)
- fungal infxn (Cryptococcus)
- lymphocytic rhinitis
- dental disease
Describe feline laryngeal/ tracheal lymphoma
- older cats (9y)
- present with URT obstruction
- dyspnoea
How common is feline CNS/ spinal lymphoma?
Describe CNS/ spinal lymphoma
- spinal or intracranial: often multiple regions affected
- intra- or extradural
- > 80% have mixed site involvement (esp renal and /or BM)
- Presentation: insidious or rapidly progressive neuro signs depending on lesion localisation
Signs of feline ocular lymphoma
- infiltrates
- uveitis
- glaucoma
Ddx - feline CNS / spinal lymphoma
- other CNS tumours (meningioma)
- trauma, intervertebral disc prolapse/ hernia
- infection: FIP, mycotic infection
- AT(E)
- discospondylitis
- FeLV-associated non-neoplastic myelopathy
What is the incidence of feline cutaneous lymphoma?
Rare in cats
What are the 2 main paraneoplastic syndromes that can be seen with lymphoma?
- hypecalcaemia
- hypergammaglobulinaemia
- (rarely: IM-disease, polyneuropathy, hypoglycaemia)
Why does hypercalcaemia of malignancy require urgent tx?
as can –> renal failure (d/t reduced RBF and /or nephrocalcinosis)
Describe hypercalcaemia of lymphoma
- 10-40% dogs with lymphoma (usually TC), rare in cats
- PU/PD d/t nephrogenic DI (Ca interferes with ADH)
- dehydration, depresson, lethargy, weakness, vomiting, consitpation, bradycardia/ bradydysryhthmias, mm tremors
Describe hypergammaglobulinaemia of malignancy
rarely, canine lymphomas have a monoclonal gammopathy d/t aberrant Ab production. Can cause hyperviscosity.
What should you do if the 1st presentation of an immune-mediated disease is when the animal is older?
check for neoplasia (i.e. immune-mediated disease of malignancy - aberrant Ab responses can trigger IMHA and IMT).
What should you focus your PE on if you suspect lymphoma?
- LN palpation (all accessible nodes, include rectal exam in dogs)
- MM
- abdominal palpation (mass lesions, organomegaly - liver and spleen, peritoneal fluid)
- thoracic auscultation, persucssion and compression (Cats)
Describe LN aspirates
- if peripheral LNs enlarge, perform LN asprates for cytology.
- often diagnostic - safe, quick, easy
- 23G needle, multiple sites
Why choose LNs other than submandibular to aspirate?
as submandibular likely to be reactive to dental dz etc
When might you do a USG-aspirate of internal LN?
- if superficial LNs not enlarged
- if liver, spleen or mediastinal mass
Describe ultrasound for feline GIT lymphoma
- HIGH GRADE: loss of normal gut layering and mass lesions, mesenteric lymphadenopathy
- LOW GRADE: muscularis propria layer often appears thick (also IBD shows this), mesenteric LNs may be enlarged but often not marked.
How do you diagnose high/low grade GIT lymphomain cats
- HIGH: do a FNA or mass lesions or enlarged LNs
- LOW (diffuse GIT thickening): full thickness biopsy needed
How do you diagnose lymphoma in cases where FNA cytology is not diagnostic/ not feasible? 4
LN, mass or organ biopsies for histopathology:
- SX BIOPSY: remove whole LN, biopsy mass, full thickness GIT tract biopsies for low grade GI lymphoma
- TRU-CUT: LNs (hard to interpret architecture), mass, liver
- ENDOSCOPE: GIT (but full-thickness may be required to get deep enough biopsies, especially feline low grade GIT lymphoma)
- PUNCH BIOPSY: skin
How useful can cytology of abdominal or pleural fluid or CSF analysis be?
can be useful
How can lymphoma be classified?
- cytological/ histopathological morphology
- grade
- immunophenotype (i.e. BC or TC)
What is the most common classification of lymphoma in dogs?
diffuse large BC lymphoma
How does immunophenotype affect prognosis in canine lymphoma?
- Intermediate and high grade lymphoma: BC better prognosis, TC worse prognosis
- more work needed to assess whether immunophenotype affects prognosis in cats
What sample is needed for immunophenotyping?
LN aspirates expressed in Cytocheck medium (a preservative)
What cell surface markers classify lymphoma?
- BC = CD79a, CD21+
- TC = CD3+, CD4+ or CD8+
Are canine lymphomas usually TC type?
No - 80% are BC origin
What immunophenotype does mediastinal lymphoma tend to be?
TC often
How does immunophenotype affect tx choice?
- DOGS - INTERMEDIATE/HIGH TC - alkylating agents (lomustine)
- TC: modified LOPP (lomustine, vincristine, procarbazine, prednisolone)
- BC: COP or CHOP
Does high/intermediate BC or TC lymphoma in dogs carry a better prognosis?
BC has better prognosis
Define PARR
= PCR for Antigen Receptor Rearrangement (aka clonality assay)
What is PARR?
- used to clarify diagnosis
- if PCR is used to amplify the DNA encoding the Ag -R region from lymphoma cells, a single band will be obtained following electrophoresis of the PCR products
- with an inflammatory/ other non-neoplastic diseae process, the population of lymphoid cells would be polyclonal. with each cell having a different piece of DNA encoding the Ag-R region. PARR analysis would give multiple bands/ a smear pattern follwoign electrophoresis
What further work up can be done after a diagnosis of lymphoma has been made?
- haematology (cell counts and smear)
- biochemistry
- urinalysis
- serum B12
- FeLV/ FIV testing inc ats
- staging
- imaging
- sampling and cytology
- BM aspirate or biopsy
What should you look for on haematology when lymphoma has been diagnosed?
- general health status: check for cytopaenias or abnormal circulating cells (BM infiltration sign). essential baseline before chemo
- anaemia often present (mild, normochromic, normocytic, non-regenerative)
- cytopaenias: if multiple cell lines affected suspected BM
infiltration - atypical circulating lymphocytes/ lymphoctyosis
What should you look for on haematology when lymphoma has been diagnosed?
- organ function ( paraneioplastic effects and prior to chemo)
- railed liver enzymes and/or bilirubin (suggesting hepatic infiltration)
- azotaemia (with renal infiltration, hypercalcaemic nephropahty or pre-renal)
- hypercalcaemia
- hyperglobulinaemia
- hypoproteinaemia (GI loss in alimentary lymphoma)
What should you look for on UA when lymphoma has been diagnosed?
- baseline info
- prior to starting cyclophosphamide (–> haemorrhagic cystitis in dogs)
Why measure serum B12 when lymphoma has been diagnosed?
often low because problems absorbing B12 and may need supplementation
Why test for FeLV/ FIV when lymphoma has been diagnosed?
FeLV + has a poorer prognosis
What is the stage of the disease?
= the extent of the disease in the body
Outline the WHO staging for canine lymphoma
1 = solitary node involved or LT in single organ
2 = involvement of multile LNs in a single region (one side of diaphragm)
3 = generalised LN involvement (both sides of diarphragm)
4 = liver and/or spleen involvement
5 = BM involvement +/- other organs (1-4)
SUBSTAGE A: no systemic signs
SUBSTRAGE B: with systemic signs (worse prognosis)
* not well suited staging system for FELINE lymphoma d/t different presentation, useful to assess extent of dz
What are you looking for with thoracic radiography in an animal diagnosed with lymphoma?
- sternal or tracheobronchial lymphadenopathy
- mediastinal mass
- interstitial/ alveolar/ nodular / mixed lung patterns
- pleural effusion
What are you looking for with abdominal radiography in an animal diagnosed with lymphoma?
- hepatomegaly
- splenomegaly
- renomegaly
- abdominal lymphadenopathy
- masses
What are you looking for with abdominal ultrasound in an animal diagnosed with lymphoma?
- changes in echogenicity of internal organs (liver, spleen, kidney)
- organ enlargement (esp liver, spleen)
- abdominal lymphadenopathy
- abdominal masses
- GI lymphoma (thickened gut wall/ masses/ loss of layering / mesenteric lymphadenopathy. Cats with low grade lymphoma have thickened muscularis propria, also IBD has this pattern. High grade - loss of normal gut layering and mass lesions. Mesenteric lymphadenopathy)
- mediastinal masses
When might BM aspirate or biopsy be indicated?
if owner wants to do full staging (abnormal circulating or cytopaenias in > 1 cell line may suggest BM involvement)
What is the minimumdatabase prior to starting tx?
haematology
biochemistry
UA
What is the most effective tx for lymphoma (broadly-speaking)?
combination chemo
systemic tx
Indications - surgical tx of lymphoma
- indications are rare
- e.g. solitary site lymphoma (good for Hodgkin’s like lymphoma in cats)
- acute intestinal obstruction
When is radiation tx the tx of choice?
- nasal lymphoma in cats (1.5-3 yr MST if respond to tx)
- some localised lymphomas
- some studies suggest whole/half body radiation along with chemo may be beneficial to consolidate and prolong remission
- rescue therapy sometimes
Outline corticosteroid use in lymphoma tx
- prednisolone and dexamtheasone –> lymphoctye apoptosis, often used in combination protocols
- alone for palliation (2-3months efficacy)
- don’t use before diagnosis
- promote MDR so if planning to give chemo, it is best not to pre-treat with steroids for a prolonged period but use them in combination from outset.
Outline chemo and lymphoma
- discuss goals with owner (remission not cure usually)
- potential adverse effects (QoL, better than humans)
- owner commitment (incl. patient temperament)
Components of COP protocol
- cyclophosphamide, vincristine and prednisolone
- tends to have induction phase + ongoing oral maintenance phase (chlorambucil, methotrexate and prednisolone)
Outline CHOP protocols
- contain doxorubicin
- more intense intially
- longer induction phase
- no maintenance phase
- e.g. Madison-Wisconsin
What does choice of protocol depend on?
- clinician and owner preference, at RVC:
- high grade canine BC lymphoma: CHOP or COP/COAP
- Intermediate to high grade TC lymphoma: modified LOPP
- high grade feline lymphoma: COP or COAP
- low grade feline lymphoma: chlorambucil + prednisolone
Mechanism - cyclophosphamide
ALKYLATING AGENT:
substitutes an alkyl group for H+ in DNA causing cross-linkage and breaking of DNA strand, thus interfering with DNA replication and transcription. Not cell cycle specific.
Mechanism - vincristine
MITOTIC SPINDLE INHIBITOR:
binds to tubulin and prevents normal assembly of microtubules. Causes arrest of mitosis in metaphase.
Mechanism - prednisolone
Cause apoptosis of lymphoid and mast cellsf
Mechanism - doxorubicin
ANTI-TUMOUR ANTIBIOTIC:
several mechanisms to prevent DNA and RNA synthesis. Inhibit topoisomerase 2, breaks DNA strands, cross-links DNA base pairs, free radical oxidative damage. Not cell cycle specific, but act more in the S-phase.
Give examples of some low-budget protocols
- prednisolone alone daily then EOD
- prednisolone as above + chlorambucil every 14d
- lomustine q21d in dogs q3-6 weeks in cats +/- prednisolone (must monitor carefully for myelosuppression, hepatotoxicity)
What should you do when lymphoma relapses after tx?
REINDUCTION AND RESCUE THERAPY:
- if animal not currently receiving tx - restart original protocol (re-induction)
- if animal is receiving a less intense maintenance protocol - go back to original inductio (re-induction)
- if relapse occurs during protocol - use new drugs that tumour has not been exposed to, preferably in combination therapy (rescue therapy)
How successful are rescue attempts than primary induction?
less successful in terms of response rates and duration
How can hypercalcaemia of malignancy (lymphoma) be managed)?
- prompt diagnosis and management of lymphoma
- saline diuresis (0.9%NaCl) at 6ml/kg/hr if no CIs
- once rehydrated, start furosemide at 1-2mg/kg to promote calciuresis
- tx underlying cause ASAP
- other meds to specifically lower Ca may help (Calcitonin, bisphosphonates).
How should lymphoma patients be monitored during chemo?
- ) regular PE for remisison/relapse
- ) haematology
- ) biochemistry
- ) B12 levels in animals with GIT lymphoma
- ) UA
- ) echocardiography
How often should haematology be done when monitoring lymphoma patients on chemo?
check for myelosuppression ideally before each tx in induction phase:
if neutropaenia of
What should be looked for on biochemistry when monitoring lymphoma patients on chemo?
- abnormal parameters
- check ALT prior to lomustine dosing
- clinical judgement for frequency
Administration route for vit B12 injection
SQ
Why do UA when monitoring a lymphoma patient on chemo?
- general health montiroing
- monitoring for haemorrhagic cystis (dogs - cyclophosphamide)
- urine dipstick and USG periodically
- remember increased infxn risk with chemo
Why perform echocardiography when monitoring a lymphoma patient on chemo?
offer prior to doxorubicin in dogs, screen for heart dz and assess FS%. Risks are higher is exceeding 180mg/m2 cumulative dose.
Describe GI disturbances following chemo
- frequently self-limiting and milkd
- if BAR, afebrile: starve for 24hr then bland diet
- may require IVFT
- anti-emetics and gut protectants: maropitant, metoclopramide, ondansetron (most potent)
What appetite stimulants might be given for anorexia d/t chemotherapy?
cyproheptadine, mirtazepine OR feeding tubes.
What to do if animal develops myelosuppression with chemo for lymphoma
- if marked neutropaenia (
What should you do if a dog with a cyclophosphamide chemo develops haemorrhagi cystitis?
- stop cyclophosphamide
- switch to chlorambucil/ melphalan
- severe and slow to resolve (sometimes irreversible)
- tx: NSAIDs if prednisolone tx has ceased
- oxybutinin anti-spasmodic,
GAGs
Prevention - haemorrhagic cystitis in dogs
- encourage water intake
- give cyclophsophamide in morning
- allow frequnecy urination during day
- if giving high dose - dive over 2d + concurrent furosemide
Which chemo drugs may elicit a hypersensitivity reaction?
L-asparaginase and doxorubicin
DOGS: urticaria, oedema, hyperaemia, V+D
CATS; respiratory distress, vomiting
What to do if chemo drug elicits a hypersensitivity reaction
stop drug tx and give antihistamine and dexamethasone
What to do if extravasation of chemo drug occurs
- leave catheter in place
- withdraw as much drug as possible
- apply ice (doxorubicin) or heat (vincristine)
- seek specialist advice
- specific drugs can minimise consequences: hyaluronidase locally for vincristine extravasation and dexrazoxane IV for doxorubicin extravasation
- anti-inflammatory doses of dexamethasone IV and topical steroid creams might be useful
What is the remission rate for canine multicentric lymphoma?
- prednisolone 33%
- COP 70-80%
- CHOP 80-94%
What is the median first remission duration for canine multicentric lymphoma?
- prednisolone 1 month
- COP 3-6 months
- CHOP 9 months
What is the MST for canine multicentric lymphoma
- no tx 4-6 wks
- prednisolone 2-3 mo
- COP 7-10 months
- CHOP 1 year (2 year survival of 20-25%)
What isthe remission rate for feline low grade lymphoma?
- COP 50-80%
- CHOP 50-70%
What is the MST for feline low grade lymphoma?
- no tx 4-6 wks
- COP 3-10 months (high) grade)
- CHOP 3-10 mo (high grade), 1 year survival at 30%
Px - feline low grade, small cell, lymphocytic TC GIT lymphoma
GOOD prognosis with chlorambucial + prednisolone (around 70% complete response rate and MST > 2years)
Px - feline high grade lymphoblastic GIT lymphoma (BC or TC)
- shorter MST 3-10 mo
Px - canine GI lymphoma. What is the exception to this?
- often poor (MST up to 77d).
- colorectal form can have prolonged survival (yrs) with COP/CHOP
Px - localised nasal lymphoma in cats with radiation tx
GOod - most respond, MST 1.5-3 years
Negative prognostic indicators for canine lymphoma
- TC immunophenotype for high grade lymphoma (half MST of BC lymphoma)
- clinical substage b (i.e. unwell)
- hypercalcaemia (likely d/t TC phenotype)
- BM involvement / stage 5
- prolonged pre-tx with corticosteroids
- failure to achieve complete remission
- SITE: GIT/ renal/ pure hepatosplenic
Negative prognostic indicators for feline lymphoma
- failure to achieve complete remission
- FeLV positive
- high grade vs. low grade
- LGL (large granular lymphocyte) lymphoma (rare variant) has v. poor prognosis
Define leukaemia
- malignant neoplasms originating from haematopoietic precursor cells in BM (sometimes spleen).
- neoplastic cells present in circulation, sometimes large #
- sometimes neoplastic cells are proliferating in marrow, causing cytopaenias, but don’t spill over into the circulation (aleukaemic leukaemia)
Define acute leukaemia
- aggressive
- rapid progression
- severe CS
- blasts in marrow or blood, poorly differentiated, high capacity for rapid division
- poor px
Define chronic leukaemia
- slow course
- CS canbe mild (sometimesincidental)
- neoplastic cells well0dfferentiated, late precursors, lesser capacity for divison
- reasonable px
Name 2 lymphoid leukaemias
- acute lymphoblastic leukaemia (ALL)
- chronic lymphocytic leukaemia (CLL)
Differentiate ALL and stage 5 lymphoma
ALL: dz starts in marrow, sicker, more profound cytopaenia, milder lymphadenopathy, poorer px vs. stage 5 lymphoma
* FLOW CYTOMETRY: identifies ALL cells positive for CD34, a marker of immature haematopoietic stem cells.
Define myeloproliferative disorders
neoplastic and possibly pre- or non-neoplastic conditions of all the non-lymphoid cells in the marrow
- uncommon
List acute myeloid leukaemias
- undifferentiated leukaemia
- myeloblastic leukaemia
- myelomonocytic leukaemia
- monoblastic leukaemia
- megakaryocytic leukaemia
- megakaryoblastic leukaemia
- erythroleukaemia
- subtypes of above
List chronic myeloproliferative disorders
- chronic myelogenous leukaemia
- eosinophilic and basophilic leukaemia
- primary thrombocytosis (essential thrombocytosis)
- polycythemia vera
CS - leukaemias
- non specific
- signs related to myelophthisis (fever, petechial haemorrhages, pallor)
- sometimes hypercalcaemia signs
Dx - leukaemia
- flow cytometry (if abnormal cells circulating, esepcially useful to determine type of cell involved)
- BM aspirate +/- core
Px - acute leukaemias
- poor response (
Tx - acute leukaemias (ALL and AML)
- ALL: potentially use same drug as lymphoma (start with l-asparaginase which isn’t myelosuppressive and pred)
- AML: try cytosine arabinosdie
Tx - chronic leukaemias
- better success rate and prognosis!
- CLL (older animals): chlorambucil + pred
- CML (rare): hydroxycarbamide (hydroxyurea)
Define myeloma
Plasma cell tumour affecting BM (or spleen) of older animals
CS - myeloma
- mild pyrexia
- lethargy
- pallor
- mild generalised lymphadenopathy
- hepatosplenomegaly
- signs of hyperviscosity (neuro signs, retinal detachment, bleeding, lameness/ bone pain)
Haematology - myeloma
mild non-regenerative anaemia, cytopaenias
Biochemistry - myeloma
- hyperglobulinaemia (often, d/t Ab production by plasma cells) –> monoclonal spike on serum protein electrophoresis
+/- hypercalcaemia
Radiographs - myeloma
- punched out osteolytic lesions (vertebrae, pelvis, long bones) or diffuse osteopaenia. Uncommon in cats.
Urine -myeloma
- Ig light chains (Bence-Jones proteinuria)
- similar pattern to serum if electrophoresis is performed
Dx - myeloma
- BM aspiration/biopsy –> increased # plasma cells
Tx - myeloma
melphalan + prednisolone (MST 12-18 mo)
- CATS: melphalan causes marked myelosuppression –> use chlorambucil + prednisolone instead, px worse in cats
What is polycythemia vera/ primary erythrocytosis?
proliferation of the erythroid cell series in the marrow, with differentiation to mature RBC
CS - polycythemia vera
- bright red MM
- neuro signs (d/t hyperviscosity)
- persistently high PCV (65-85%)
- low/normal erythropoietin activity
What do you need to differentiate polycythemia vera from?
- dehydration
- appropriate causes of incresed RBC (hypoxia)
- EPO producing tumours
Tx - polycythemia vera
phlebotomies and replacement of blood with colloids/ electrolytes to alleviate hyperviscosity; hydroxycarbamide (= hydroxyurea)
