Hematopoietic Tumours Flashcards
1
Q
Which breeds are predisposed to LSA?
A
boxer, bull mastiffs, St. Bernard’s, Rotties, Basset hounds, Scottish Terriers, Airedale, pitbulls, Briards, Irish Settlers, bulldogs
2
Q
Which genetic mutation actually provides an survival advantage for dogs with LSA?
A
trisomy 13
3
Q
Which somatic mutations have been implicated for Goldens with lymphoma?
A
Alteration/ deficiency in DNA repair mechanisms
4
Q
What’s the risk of developing LSA in cats undergoing organ transplantation with cyclosporine?
A
24% risk of developing cancer; 36% = LSA
5
Q
What are the 4 most common anatomical forms of LSA in the dog?
A
- multicentric (>80%)
- GI (5-7%)
- mediastinal (5%)
- cutaneous
6
Q
What are some primary extranodal sites for LSA?
A
- eyes
- skin
- CNS
- bone marrow
- bladder
- heart
- nasal cavity
7
Q
What are some presentations of GI LSA in the dog?
A
- often it’s a focal mass
- but can also have segmental infiltration, with involvement of the mucosa, submucosa, and even transmural infiltration
- can have mural thickening, narrowing of the lumen, and frequent mucosal ulceration
8
Q
What’s the most common immunophenotype for GI LSA?
A
T cell
9
Q
Which breeds are predisposed to GI LSA?
A
Boxers and Shar-pei
10
Q
What are the differentials for GI LSA?
A
- IBD
- plasma cell tumour
11
Q
What is mediastinal lymphoma?
A
enlargement of the cranial mediastinal LNs, thymus, or both
12
Q
What’s the most common paraneoplastic syndrome for mediastinal lymphoma?
A
Hypercalcemia –> seen in 10-40% of dogs with mediastinal LSA
- 43% (16/37) of dogs with LSA that also have hypercalcemia have the mediastinal form
13
Q
What’s the most common immunophenotype of mediastinal LSA?
A
T cell
14
Q
What are the 2 forms of cutaneous LSA?
A
- epitheliotropic (mycosis fungoides)
- non-epitheliotropic
15
Q
What’s the most common immunophenotype for cutaneous LSA?
A
T cell; specifically CD8+
(CD4+ is more common in people)
16
Q
What’s Sezary syndrome?
A
T-cell epitheliotropic LSA with large malignant T cell in circulation
17
Q
What’s the histological distinction for non-epitheliotropic cutaneous LSA?
A
- only involves the middle and deep portions of the dermis and subcutis
- spares the epidermis and papillary dermis
18
Q
Which form of cutaneous LSA can be difficult to differentiate from reactive histiocytosis?
A
inflamed form of non-epitheliotropic cutaneous LSA
19
Q
Describe hepatosplenic lymphoma.
A
- uncommon
- infiltration of the liver, spleen and bone marrow
- no significant peripheral lymphadenopathy
- very aggressive with poor response to therapy
- mostly T cells
20
Q
What is intravascular lymphoma?
A
- proliferation of neoplastic cells from the lumen or the walls of blood vessels
- no extravascular mass or leukemia
- in humans = B cells
- in dogs = T or null cell
- usually involves the CNS, PNS, or eyes
21
Q
Describe pulmonary lymphatoid granulomatosis.
A
Rare cancer of the lungs involving both T and B cells, with other white blood cells arranged angiocentrically
- response to various chemo protocols range from rapid progression to prolonged remission
22
Q
Which LSA is considered indolent LSA?
A
- follicular
- marginal zone
- T-zone lymphoma
- B cell rich T cell LSA
- B or T cell small cell LSA
23
Q
What’s the most common form of canine LSA?
A
diffuse large cell B cell lymphoma (high grade)
- low grade = 5.3-29% of cases
24
Q
What are some breed predisposition to B and T cell LSA?
A
B cells: cocker spaniels, and Dobbies
T cells: boxers
Goldens = equal likelihood between B and T
25
What's the immunophenotype distribution of canine LSA?
- 60-80% = B cell
- 10-38% = T cell
- null-cells <5%
26
What's the percentage of dogs with multicentric LSA with radiographic evidence of lung involvement (diffuse pulmonary infiltration)?
27-34%
27
What are some clinical signs of mediastinal lymphoma?
- respiratory compromise --> exercise intolerance, regurgitation, pleural effusion
- PU/PD from the hypercalcemia
- precaval syndrome: tumour compromises the cranial vena cava --> pitting edema (head, neck, forelimbs), facial edema
28
What are the 3 stages of epitheliotropic lymphoma?
1. alopecia, scaling, pruritus
2. erythematous, thickened, ulcerated, and exudative
3. proliferative plaques and nodules with progressive ulceration
29
How does the oral involvement look like for cutaneous lymphoma?
- multicentric erythematous plaque-like hypopigmented lesions
- nodules associated with the gums/ lips
30
How do the lesions appear with non-epitheliotropic lymphoma?
- single or multiple dermal/ SQ nodules or plaques
- may be non-pruritic, ulcerated, or alopecic with crusts
- usually occur on the face, lower extremities, neck, and trunk
31
What are some typical involvement noted with CNS lymphoma?
- solitary or multifocal involvement
- most = secondary invasion
- B cell = more common --> meningeal, perivascular, and peri-ventricular location
- T cell more likely seen with peripheral nerves
32
What are some clinical signs of CNS lymphoma?
- seizure
- paralysis
- paresis
33
What are some involvement/ clinical signs of ocular lymphoma?
- thickened iris
- glaucoma
- posterior synechia
- hypopyon
- hyphema
- uveitis
34
How often does multicentric LSA involve the eyes and how often is uveitis part of LSA?
- 37% dogs with multicentric lymphoma have ocular involvement
- 17% of dogs with uveitis is secondary to lymphoma
35
What's the prognosis of primary ocular lymphoma?
MST = 769d (25m)
compared to part of multicentric form = 103d (3.5m)
- no progression after enucleation
36
What's the most common immunophenotype for ocular lymphoma?
Peripheral T cell and DLBCL = most common
37
What's the most common ocular presentation of stage V multicentric LSA?
anterior uveitis
38
What are some signs of primary hepatosplenic LSA?
icterus = often
and non-specific signs like lethargy, anorexia, and weakness
39
What's the most common paraneoplastic syndrome for canine lymphoma?
anemia
40
What are some other paraneoplastic syndrome associated with lymphoma?
- hypercalcemia
- neuropathies
- monoclonal gammopathies
- cancer cachexia
41
What's the pathophysiology of hypercalcemia in dogs with LSA?
- most likely due to PTHrP
- but can also be due to other humoral factors: IL-1, TNF-alpha, TGF-beta, vitamin-D analog
42
What are some differentials for peripheral lymphadenopathy?
- infectious: bacterial, viral, protozoal (Toxoplasma), rickettsial (Erlichia, salmon poisoning), fungal (Blasto, histoplasma)
- immune-mediated: usually just mildly enlarged
- metastatic
43
What % of dogs with lymphoma will have thrombocytopenia?
30-50%
44
What % of dogs with lymphoma will have neutrophilia?
25-40%
45
What % of dogs with lymphoma will have lymphocytosis?
20%
46
What % of dogs with lymphoma will have monoclonal gammopathy?
6%
47
How often is monoclonal gammopathy noted in B cell LSA?
infrequently
48
What's the diagnostic yield of CSF for CNS lymphoma?
74% (in 27 samples)
- most have increased cell counts, with 95-100% atypical lymphocytes
49
What are some IHC for B cell LSA?
CD79a, CD20, CD21
49
What's a limitation of flow cytometry for CSF?
needs at least 10,000 cells
50
What are some IHC for T cell LSA?
CD3, CD4, CD8
51
Which LSA is positive for CD21?
B cell LSA
T-zone lymphoma
51
What's the sensitivity of PARR?
70-90%
51
What are some reasons for false negative on PCR?
- clonal segment of DNA is not detected by the primer
- mutation of the primer
- background noise
- too few neoplastic cells
- natural killer cell LSA
52
What are some reasons for false positive for canine LSA from PARR?
- infectious causes (Erlichia)
53
What's the % of abnormalities noted on CXR for canine LSA?
60-75%
1/3 = pulmonary infiltrates
2/3 = sternal lymphadenopathy
- cranial lymphadenopathy is noted in 20% of dogs with lymphoma
54
What's the % of abnormal abdominal x-rays for dogs with lymphoma?
50%
- sublumbar lymphadenopathy
- mesenteric lymphadenopathy
- liver, spleen
55
What's an unique IHC stain for T zone lymphoma?
it's CD45-!
56
What's the prognosis of T zone LSA?
Good! MST = 21m
They present like multicentric T-cell LSA, but mostly small to intermediate, and have a more indolent behaviour
- Goldens and Shih Tzu
57
What are some examples of indolent lymphoma?
B cells:
- marginal zone LSA: intermediate sized cells; can have a splenic form
- mantel cell LSA: spleen, small to intermediate size
- follicular/ nodular LSA: mixed but mostly small; can transform
58
What's the general response to CHOP for multicentric lympoma?
80-95% RR
MST: 10-12m
Approximately 20-25% will liver >2y
59
What are the fundamental treatment goals for multicentric LSA?
- induce durable remission (>6m)
- re-induce (with the same protocol) with relapse
- if still doesn't work then use a rescue
60
What's the role of maintenance protocol for treatment of multicentric lymphoma?
no clear advantage shown - PFI is about the same
- better to stick with a defined protocol that's not prolonged
- appear to respond better (compared to those with maintenance) to rescue after relapse
61
Does incorporation of other drugs that have shown single agent effects to CHOP change the survival outcome?
no, nothing that has been adequately evaluated.
- mostly reserve for rescue setting
62
What are some indications for rabacfosadine?
- multicentric lymphoma
- multiple myeloma
- cutaneous lymphoma (PFI = 37.5d, ORR = 45%)
- can also be combined with doxorubicin
63
What are the most common side effects with rafacfosadine?
- diarrhea
- decreased appetite
- vomiting
64
What's the outcome of rabacfosadine for treatment naive multicentric lymphoma?
- RR = 87%: B cell = 97%, with 62% CR. T cell = 50% with 22% CR
- PFI = 122 d (4m); 199d (6.5m) if experiencing CR
- pre-treatment with steroids and T-cell = worse
- 3 (6%) grade V pulmonary fibrosis(>4m later)
(Saba et al 2020)
65
What's the outcome of rabacfosadine alternating with doxorubicin for treatment naive canine lymphoma?
ORR = 84-93%
PFI = 194-199d (~6m)
Negative prognostic factors = T cell (PFI = 2m) and lack of response
(Saba et al 2024, prospective)
66
What's the response rate for rabacfosadine + Elspar as a rescue for multicentric lymphoma?
- ORR = 67% with 41% CR
- median PFI = 63d (2m), if CR, then 144d (4m)
- negative prognostic factors = no CR, and previous Elspar use
(Cawley et al 2020)
67
What's the outcome of rabacfosadine for relapsed B cell lymphoma?
either 1mg/kg or 0.82mg/kg
- ORR = 75%, with 45% CR
- median PFI = 108d (3m), CR = 203d (~7m)
- still had 1 with grade 5 pulmonary fibrosis
(Saba et al 2019)
68
What's the outcome of Verdinexor for canine cutaneous LSA?
- 75% response rate
- average PFI = 56d (2m)
- pruritus didn't improve
69
What's the outcome of verdinexor for canine lymphoma?
- ORR = 37%
- median TTP = 43 days for naive, 23 days for relapsed
- TTP for T cell = 43d!
(Sadowski et al 2018)
70
What's the most common AE for verdinexor?
- anorexia
- weight loss
- vomiting
- lethargy
- diarrhea
(Sadowski et al 2018)
71
What's the outcome for single agent doxorubicin for canine lymphoma?
RR = 50-75%
MST = 6-8m
72
What's the outcome with cyclophosphamide and doxorubicin for canine lymphoma?
With adding cyclophosphamide for 3 days with each doxo, the PFS is 8.2m vs 5.6m, but it was not statistically significant
73
What's the outcome of CCNU and prednisone for naive canine lymphoma?
ORR = 87%, 50% CR
median DFI = 63d (2m); not significantly different between T and B cell
MST = 90d (3m); also no difference between B- and T- cell
- stage was significantly associated with outcome
(Catalucci et al 2024)
older 2007 study (Sauerbrey et al)
- MST = 111.2d (4m)
74
What's the response of CCNU in a rescue setting for canine lymphoma?
RR = 28%, CR in 7%
average time to response = 86d (3m)
(Moore et al, 1999)
75
What's the outcome of T cell LSA treated with CHOP?
MST = 159d (5m), compared to non-T cell, 389d (~1y)
76
What's the outcome of substage B patients treated with CHOP?
MST = 44d, compared to substage a, 345d (~1y)
77
What are some causes of relapse/ drug resistance?
- MDR status
- inadequate dosing
- privileged sites
78
What the general reinduction rates for dogs who had a durable remission with the first CHOP (with another CHOP protocol)?
80-90%
79
What's the overall rescue response rate and outcome?
- 40-90%
- median response duration: 1.5-2.5m
- <20% will enjoy a more durable remission (ex. if achieving CR)
80
What are some outcome of various rescue protocols for lymphoma?
- Anthracycline/ CHOP around 80%
- LOPP ~90%
- CCNU ~ 50%
81
What's the standard of care for people with B-cell LSA?
R-CHOP
R = rituximab --> targets CD20, but not effective in dogs (1. it's murine/human chimeric antibody, 2. lack of external recognition of similar antigen on canine lymphocytes)
82
What's the potential immunotherapy target for canine lymphoma?
anti-CD20 mAB or vaccine
CAR-T therapy is also another upcoming hot topic
83
What's the outcome for CHOP in naive canine lymphoma?
CR in 78%
median remission = 10m
(Flory et al 2011)
84
What's the outcome of splenectomy for dogs with splenic lymphoma?
1y survival rate = ~60% (for B cell = 78%)
- if T or others, MST is 2 days
- pre or post-op chemotherapy didn't provide survival benefit
- negative prognostic factors: hemoabdomen, substage B (abdominal distension, anorexia, lethargy)
(vet surg 2015)
In JVIM 2013:
- MST for none clinical MZL = 1153d (3y), clinical = 309d, with overall MST = 383d
85
What's the prognosis of canine nodal marginal zone lymphoma?
median TTP = 149d (5m)
LSS = 259d (8.7m)
- all dogs had peripheral lymphadenopathy and 1/3 was clinical
- mostly stage V (peripheral blood and bone marrow involvement)
(Cozzi et al 2018)
86
What are 4 indications for RT in canine lymphoma?
1. stage 1 or extranodal setting (ex. nasal lymphoma)
2. palliative RT (ex. stubborn LN, mediastinal LSA with pre-caval syndrome)
3. TBI with bone marrow or stem cell transplant
4. HBI as part of consolidation
(when used as rescue setting was not helpful in a pilot study with 7 dogs, single fraction TBI)
87
What's the outcome of alimentary lymphoma in dogs?
Generally high grade, diffuse use, and MST of only a few months with chemo (though a small population can survive longer)
- if solitary, surgery +/- chemo can have good outcome
88
What's the outcome of canine rectal lymphoma?
they tend to be high grade, B cell, but with chemo, MST >3y
89
What's the outcome for canine small cell T cell alimentary LSA?
with conservative treatment (prednisone and chlorambucil most commonly), can still have MST 1.5-2y
90
What's the outcome of primary CNS LSA in dogs?
primary CNS LSA = rare
- has tried intrathecal Ara-C, with RT and systemic chemo, an the response is still short-lived (weeks to months)
- occasionally can have more durable response
91
What are some prognostic factors for canine cutaneous lymphoma?
true cutaneous LSA tend to have multiple lesions (90%)
- MST = 130d (4m), solitary = 231d (7.5) vs multiple = 72d (2m)
- MST for those recevied chemo ~ 6m, no chemo = ~2m
- use of retinoids improved survival (MST = 251d/ 8.4m)
Mucosal/mucocutaneous LSA, 76% = solitary
- MST = 491d (16m), solitary = 849d (28m); multiple = 241d (8m) majority had surgery
- did not find LN status or substage effecting ST
92
What's the general outcome of canine cutaneous lymphoma treated with CCNU?
RR = (40% to) ~80%
Median PFI ~ 100days (3-6m)
93
What's the outcome for mucocutaneous LSA in dogs treated with radiation therapy (8Gy weekly x 3-4 fx)?
for disease confined to the oral cavity or local regional LN
- MST = 770d (25m/2y)
94
How does MCH II expression influence outcome of B cell LSA?
MST = 120d vs 314d with high MCH II expression (4m vs 11m)
- also has shorter remission time
95
How does B5 antigen expression influence outcome in canine lymphoma?
lower B5, PFI = 125d vs 202d (4m vs 7m)
96
What are the most consistent prognostic factors for canine multicentric LSA?
- immunophenotype
- substage
- indolent classification
97
What's the outcome of indolent cutaneous T cell LSA in dogs?
with just steroids, can have prolonged survival (years)
98
Which anatomic sites for lymphoma in generally associated with poor prognosis?
- primary CNS
- diffuse cutaneous
- hepatosplenic
- diffuse GI
99
What are some other prognostic factors reported in canine nodal LSA that have strong association?
- immunophenotype
- high grade/ indolent
- anemia
- steroid pre-treatment
- anatomical site
- cranial mediastinal lymphadenopathy (B cell: 10 vs 6m; T-cell: 6 vs. 3m)
100
Which breeds are more likely to have B cell CLL?
small breeds
101
Which breed may have its own entity B cell CLL?
English bulldogs
- they tend to be younger on presentation (6y vs 11y)
- have lower expression of CD25 and MHC II
(Bromberek et al 2016)
But this may be a polyclonal B cell lymphocytosis! (Rout et al 2020)
102
What's the immunophenotype distribution of canine CLL?
2/3 = T cell
1/3 = B cell
(in people it's mostly B cell)
103
What are the 3 forms of CLL?
1. T cell (CD3+) = most common
2. B cell = 2nd most common
3. Atypical: CD3-, CD8+; CD3+, CD4-, CD8-; CD3+, CD4+, CD8+; CD3+, CD21+
104
How do the lymphocytes look for CLL?
they look like mature, normal small lymphocytes
105
How do the lymphocytes look in ALL?
- large
- high N:C ratio
- basophilic cytoplasm
- the chromatin pattern is less condensed than mature lymphocytes but more than myeloblasts
106
What's the distribution of immunophenotype for ALL?
mostly B cell (CD21+, CD3-, CD4-, CD8-)
- <10% are T cell (CD3+, CD4-, CD8-, CD21-)
107
Which IHC can be useful to determine an acute phenotyep?
CD34
- but some T-ALL don't express CD34
108
Can CD34 differentiate between ALL and AML?
no, both myeloid and lymphoid lineage will express CD34
- so will need to rely on other IHC markers for T cell or B cell
- myeloperoxidase (myeloid marker)
- some T-ALL don't express CD34!
109
What's the incidence of other findings (other than lymphocytosis) in B-CLL?
- 50% some degree of peripheral lymphadenopathy
- 50% splenomegaly
- 30% hepatomegaly
- 23% visceral lymphadenopathy
- 3% mediastinal mass
110
What's the CBC like for most dogs with CLL?
usually hemogram and granulocytes are have few abnormalities with lymphocytosis <30k
111
What are some reported paraneoplastic syndromes for CLL?
- monoclonal gammopathy (IgM or IgA)
- hypercalcemia
- IMHA
- pure red cell aplasia
112
What are some presenting signs for ALL?
- anorexia
- weight loss
- lethargy
113
What are some PE findings for ALL?
- splenomegaly = typical
- can also have hepatomegaly, lymphadenopathy, hemorrhage
- can have extranodal infiltration (CNS, bone, GI) --> neuropathy, pain, GI signs
114
What are some CBC abnormalities?
can have extensive neoplastic cell infiltration in the bone marrow --> severe anemia, neutropenia, thrombocytopenia
115
What's the normal composition of circulating lymphocytes?
80% T cell
15% B cell
the rest are NK cells and double negative T cells (CD3-, CD4-)
116
What are the composition of the circulating T cell fraction?
mostly helper T cells (CD4+)
117
What are some clues to indicate leukemia?
- atypical lymphocytes in circulation
- homogenous immunophenotype
- increased # of immunophenotype over normal
- monoclonal (PARR)
118
What are some non-cancerous differentials for lymphocytosis?
- infection (ex. Erlichia)
- post-vaccine in young dogs
- IL-2 administration
- transient epinephrine induced or physiologic induced
119
How much infiltration of neoplastic cells can be noted in the bone marrow for early T or B cell CLL?
> 30%
- T cell CLL will have pink granules occasionally
120
What's the most common treatment protocol for CLL?
Chlorambucil + prednisone
- 0.2mg/kg or 6mg/m2 daily x 7-14d
- then 0.1mg/kg or 3mg/m2 daily thereafter
- or do 2mg/m2 EOD long term
- prednisone = 1mg/kg then 0.5mg/kg
- can substitute with cyclophosphamide or add vincristine if not responding
121
What's the outcome of CLL with treatment?
MST 1-3y
122
What's Richter's syndrome?
when CLL progresses into rapidly progressive phase
- pleomorphic large lymphocytes
- lymphadenopathy
- vomiting
- coughing
- weight loss
- neurologica signs
123
What's the prognosis after development of Richter's syndrome?
poor
- one study reported time to Richter's 2-16m
- MST of only 41d despite CHOP
124
What's the treatment for ALL?
they can be quite sick from myelophthisis
- supportive therapy
- whole blood transfusion, IV antibiotics, nutritional support
- despite aggressive therapy (CHOP-like), response and durability = limited
(in people it's bone marrow ablation with stem cell or marrow replacement)
125
What's the MST for B-CLL, T-CLL, and atypical CLL?
B-CLL = 480d (1.3y)
T-CLL = 930d (2.5y)
atypical CLL = 22d (3 week)
- this study also found anemia and young age to the negative prognostic factors
(Comazzi et al 2010)
126
What's the influence of degree of lymphocytosis for CD8+ CLL?
< 30K, MST = 1098 (3y)
>30k, MST = 131d (4m)
(Comazzi et al, 2010)
127
What % of dogs with CLL will have normalization of lymphocyte counts?
70%
128
What's the prognosis if CD21+ ALL?
129 days (4m), despite CHOP
129
What's the outcome of ALL treated with cyclophosphamide and prednisone?
CR and PR in 29%
MST = 120d (4m)
130
What are the most common form of lymphoma in the cat?
1. Alimentary/ GI
2. Peripheral/ nodal
3. Extra-nodal
131
How do indolent lymphoma in cats respond to chemotherapy?
Most chemo = chlorambucil and prednisolone
- response rate = high
- durability = long
- ST = >1.5-3y
132
How do intermediate/high grade lymphoma in cats respond to chemotherapy?
RR = 50-65%
- if not in CR, <1y
35% will have CR
- those in CR can live >1y
133
What form of lymphoma is predisposed in Siamese/ oriental breeds?
Mediastinal
not associated with FeLV status
tend to be younger (<2y)
134
How is the signalment different between the FeLV era and post-FeLV vaccine era for cats with LSA?
FeLV era:
- young, 3-5yo, predominantly mediastinal forms
Post-FeLV era:
- older, 11-12yo, alimentary form more common
Can still see younger cats with mediastinal form that is FeLV (+)
135
With which immunophenotype is FeLV proviral insertion more common?
T cell, particularly in the thymus or peripheral lymph nodes
136
Which immunophenotype is more common with FIV associated lymphoma?
B cell
(FIV plays a more indirect role compared to actual tumorigenesis with FeLV)
137
What's the immunophenotype and prognosis of the following forms of feline lymphoma?
- GI, low grade, intermediate, granular
- Nasal
- Mediastinal
- Hodgkin's
- Renal
- Ocular
GI
- low grade, T cells small, good
- intermediate/ high grade, B cell, poor-fair
- large granular, T cells, poor
Nasal, B cells (75%), good
Mediastinal, T cells, poor-fair
Hodgkin's, T cell rich B cell large, good-fair
Renal, B cells, poor-fair
Ocular, B cells, good
138
What % of cats develop LSA after organ trasnplant?
10%, all intermediate-large B cell LSA
139
What's the most common neoplasia in the feline GI tract?
Lymphoma
140
Where intestinal lymphoma most commonly located?
Small intestine
141
What's the most common colonic neoplasia in the cat?
adenocarcinoma
142
What are the 3 forms of GI LSA?
1. low grade/ small cell
2. intermediate-large cell
3. large granular cell
143
Which is more likely - solitary or diffuse GI LSA in the cat?
Diffuse is more likely but solitary can occur
144
What organs are involved in feline GI lymphoma?
1. gastric/ intestinal
2. or combination of intestinal, mesenteric LNs, hepatosplenic
145
Describe low grade alimentary lymphoma.
- mostly T cell (esp confined to the small intestines, 94%)
- gastric involvement = B cell
- most low grade LSA have epitheliotropism, and are mucosal
- the high grade, large cell, tend to be transmural --> mostly B cells, just over 50% of T cell will have large cells
146
How often are liver and mesenteric LNs involved in low grade GI lymphoma?
53% liver
33% LNs
147
What's the cell size/ immunophenotype distribution of low grade GI lymphoma?
80% small cell, 20% large cell
> 80% CD3+ T cell
148
What's the WHO EATCL classification for low grade GI LSA?
Type II (mucosal) - 90%
Type I (transmural) - 10%
149
What's the RR and outcome for low grade GI lymphoma?
>80%,
MST = 1.5-3y
150
Where do low grade GI lymphoma arise?
mucosal associated lymphoid tissues (MALT)
151
Which cells do the intermediate/high grade alimentary LSA arise from?
MALT, Peyer's patches, and mucosal lymphoid nodules
152
Which sites are more common for intermediate/high grade alimentary lymphoma?
- stomach
- distal small intestine
- cecum
- colon
153
Describe intermediate/high grade alimentary lymphoma?
- ~ 100% CD79a+ B cell
- >90% intermediate/large cell
- WHO EATCL type I (transmural)
- epitheliotropism = rare
154
How is intermediate/ high grade alimentary LSA presented (solitary or diffuse)?
Solitary and simultaneous involvement of stomach, small intestines, and ileocecal junctions can occur
155
What's the RR and outcome for intermediate/ large alimentary lymphoma?
RR = 50-60%
CR ~ 30%
MST = 3-10m, longer if CR
156
What's the distinguishing cytological features of large granular lymphoma?
large lymphocytes with magenta or azurophilic granules
157
What's the most common site for NK-cell large granular lymphoma?
small intestine, especially the jejunum
transmural
has epitheliotropism
158
What are some common organ involvement for NK-cell large granular lymphoma?
2/3 of the cases will have other organ involvement
- mesenteric LNs = most common
- spleen, liver, kidneys, abdominal effusion, bone marrow
- pleural effusion, mediastinal mass
159
How frequent is peripheral blood involvement in large granular lymphoma?
10-15%, and up to 86% in one report
160
What's the most common immunophenotypes for large granular lymphoma?
- mostly cytotoxic T cell: CD3+, CD8+, CD79a-
- or NK cell: CD3-, CD79a
- often granzyme B+ and CD103+
161
What's the RR and outcome of large granular lymphoma?
RR = 30%
MST = 45-90d (1.5-3m)
162
What are the most common clinical signs of low grade GI lymphoma?
- weight loos (>80%)
- vomiting/ diarrhea (70-90%)
- icterus = uncommon (7%)
163
What are some common clinical signs of intermediate-high grade GI lymphoma?
- GI signs like low grade GI LSA, but progresses more quickly
- may be able to feel abdominal mass/ LNs
- icterus is more common
- hematochezia or tenesmus possible with colonic involvement
- rarely present with acute abdomen
164
What are some common clinical signs of granular cell GI lymphoma?
- similar GI signs as the other forms
- but more likely to present acutely
- up to 10% will have abdominal and pleural effusion
- ~50% will have a palpable abdominal mass
- hepatomegaly/ splenomegaly
165
How often is circulating neoplastic cells noted with GI lymphoma?
- low grade = rare
- intermediate/ high grade or granular cell = 15%
166
How often is hypoproteinemia and anemia in GI lymphoma?
up to 23% will have hypoproteinemia and 76% will have anemia
167
What are the most common changes noted with low grade GI lymphoma?
- there is usually preservation of wall thickening
- muscularis and submucosa most commonly affected
- modest intestinal thickening
- mass lesion = uncommon
- mesenteric lymphadenopathy present in 45-80%
- mild effusion possible
168
How is low grade GI lymphoma diagnosed?
- will need histology most likely as cytology is difficult to differentiate from LPE
- full thickness preferred
- endoscopic biopsies may still be diagnostic, especially if adding in IHC, PARR
169
How is intermediate/high grade and granular cell lymphoma diagnosed?
- usually based on PE and AUS findings
- cytology is usually good enough (mass, LN)
- most of intermediate/ high grade LSA are found in the stomach and colon compared to granular cell LSA, and all will have either a mass present or wall thickening
- 20% will have abdominal lymphadenopathy
170
What's the treatment for low grade GI lymphoma?
Chlorambucil (20mg/m2 PO every 2-3 weeks OR 2mg/m2 PO EOD) with tapering dose of prednisolone (1-2mg/kg PO daily then 0.5-1mg/kg EOD over a few weeks)
171
What's the MST with rescue protocols for low grade GI lymphoma?
MST = 9-29m
172
What are some rescue protocols for low grade GI lymphoma if no longer responding to chlorambucil?
- cyclophosphamide 200-250mg /m2 PO every 2-3 weeks
- lomustine
- vinblastine
- CHOP/ COP
173
What are some prognostic factors for low grade GI lymphoma?
- not well defined
- maybe lack of initial response to treatment
- maybe transmural involvement
174
What's the treatment for intermediate/high grade or granular LSA?
CHOP/COP
- single agent doxorubicin (25mg/m2 or 1mg/kg q3w x 5 treatments) --> watch for renal toxicity
- lomustine (40-50mg/m2 q3w)
- prednisone
175
What's the response of intraperitoneal COP?
- small study (n=20), 3 GI lymphoma, all large cell
- 76.9% CR
- 1st remission duration = 421d
- MST = 388d (~1y)
176
What's the remission rate and outcome of intermediate/ large GI lymphoma?
- Remission rate = 50-65%
- if CR = 7-10m
- rescue protocols or reinduction with CHOP = not durable remission
177
What are some prognostic factors for intermediate/ large GI lymphoma?
#1 = response to therapy --> ie. achieving CR
- transmural involvement
- weight loss
- elevated LDH
- hypoproteinemia, hypocobaliminia
- bicavitary involvement
178
Which factors are not prognostic for intermediate/high grade GI lymphoma?
immunophenotype
proliferating indices (ex. PCNA, AgNOR, Ki67)
179
What's the outcome of granular cell GI lymphoma?
- 1/3 will respond
- MST 21-90d
- 7% may live longer (<6m)
- another small study (n=6) had 9m with various intervention
180
What's the outcome of intermediate/ high grade GI lymphoma with surgery?
MST = 417 (14m)
PFI = 357d
- only clinical stage was prognostic
(Gouldin et al 2017)
181
What's the role of RT in GI lymphoma in cats?
in one study with 11 cats (6 small cell, 4 large cell, 1 granular) in relapsed/ resistant setting
- 10/11 responded
- MST = 214d (7m)
- 8Gy in 2 over 2 days
Another study consolidation study (CHOP followed by 1.5Gy x 10fx) with 8 cats, 7 intermediate/large cell
- 3 cats died within 3 weeks, but 5 had durable remission (>266d)
In a 3rd study with lomustine followed by RT, MST = 101d (3m), 50% RR. Similar to chemo alone
(Gieger et al 2021)
182
How common is lymphoma that is limited to the peripheral LNs only in cats?
- only 4-10%
- but ~25% of other anatomical forms of LSA will have some peripheral nodal involvement
183
In what age group would peripheral nodal lymphoma be more common in cats?
<1y
184
What are some common presenting signs for cats with peripheral nodal LSA?
depression, lethargy
185
What are some common signs of cats presenting with Hodgkin's like LSA?
usually no overt clinical signs! other than enlarged head/ cervical nodes.
- can also have inguinal, multicentric, and SQ, and ocular involvement
186
What's the key cytological features of Hodgkin's like LSA?
Reed-Sternberg-like cells!
- they are bizarre or multinucleated cells
187
What' the immunophenotype of Hodgkin's like LSA?
T cell rich B cell LSA
188
How is peripheral nodal LSA treated in cats?
- if low grade/ indolent = chlorambucil, prednisolone
- if intermediate/ high grade = CHOP/ COP
189
How is Hodgkin's like LSA treated in cats?
- Sx or RT if not too many nodes involved
- MST ~1y
- eventual recurrence at more distant nodes = common
- can consider chlorambucil/ pred after surgery
190
What organs are involved with mediastinal LSA?
thymus, mediastinal and sternal LNS
191
What is the signalment of a group of cats that have biologically less aggressive mediastinal LSA?
young Siamese, FeLV negative
- also more responsive to chemotherapy than FeLV + cats
192
How common is other anatomical site involvement in mediastinal LSA?
it's primary located within the mediastinum
193
How often is mediastinal LSA diagnosed in cats with mediastinal disease/ pleural effusion?
63% of cats with mediastinal disease and 17% of cats with pleural effusion = mediastinal LSA
194
What's the typical presenting signs for mediastinal lymphoma?
- Dyspnea (80%)
- tachypnea
- non-compressible cranial thorax
- dull heart sounds
- effusion present in 50% of cats
- Horner's, precaval syndrome, and hypercalcemia = rare
195
What's the main differential for pleural effusion in cats?
Chylous effusion
- need to measure serum and fluid triglycerides (pleural effusion should have higher triglycerides than serum for chylous effusion, though anorexic cats may have lower triglycerides in pleural effusion)
196
What's are the differentials for mediastinal mass?
thymoma
lymphoma
- 50% of thymoma cytology will have MCT, but can have lots of lymphocytes
197
What's the outcome for mediastinal LSA?
with CHOP or COP,
RR = 95%
MST = 373d
if CR = 980d
198
What's the incidence of hypercalcemia in cats with lymphoma?
10%
199
What's the sensitivity of PARR for diagnosing LSA in cats?
80%
200
Describe the staging system for feline LSA.
- majority of GI LSA = stage 3
201
What's the most common extranodal LSA in cats?
nasal
202
How common is regional or distant spread for nasal LSA in cats?
up to 20% at necropsy
203
Which breeds may be overpresented for feline nasal lymphoma?
Siamese
204
What's the most common immunophenotype for feline nasal lymphoma?
75% B cell
- T cell and mixed B- and T- cell make up 10-15%
205
What's the "grade" of feline nasal lymphoma?
- mostly large cell
- though up to 25% = small cell
206
What are the most common clinical signs for feline nasal LSA?
- nasal discharge
- sneezing
- upper resp noise
- facial deformity
- hyporexia
- epiphora
- increased resp effort and coughing
207
How often is epistaxis in cats with nasal LSA?
up to 1/3 of cats with nasal discharge (generally mucupurulent)
208
How often is IHC needed to differentiate nasal LSA from adenocarcinoma in cats?
7%
209
What's the treatment of choice for stage I feline nasal lymphoma and what's the outcome?
RT! need total dose >32Gy
CR = 75-95%
MST = 1.5-3y
MST = 4.5m if no response
210
If RT is not available, what's the alternative treatment for feline nasal LSA?
CHOP/COP
CR = 75%
MST ~ 2y with CR
211
What's the outcome of feline nasal LSA without treatment?
MST = 53d (2m)
212
Does adjuvant chemo after RT for stage I nasal LSA improve ST?
no
213
What's the 2nd most common form of extranodal LSA in cats?
renal!
214
What's the most common immunophenotype of renal lymphoma in cats?
B cell, large cell
215
How common is renal lymphoma confined to the kidneys only?
<25%
- most would be part of alimentary or multicentric
216
What are the most common clinical signs for cats with renal lymphoma?
signs associated with renal insufficiency:
- hyporexia
- weight loss
- PU/PD
217
What are some common PE findings for cats with renal lymphoma?
- marked renomegaly - bilateral, usually lumpy
- can also see on x-rays
- AUS -- bilateral renomegal (>80%) with hypoechoic subcapsular thickening
- diffuse renal cortical changes
- 1/3 will have u/s abnormalities in other viscera
218
What's the outcome with feline renal LSA?
similar to intermedaite-large cell alimentary LSA
- treat with COP (use dox only when in remission when renal values normalize)
- 2/3 will respond
- MST = 4-7m
219
How common is CNS lymphoma in cats?
80% is secondary with multicentric involvement (esp bone marrow and kidneys)
220
How common is multiple spinal lyphoma in cats?
40%
221
How often would CNS lymphoma in cats with multicentric and extracranial disease?
2/3
222
How often is lymphoma in cats with seizures and intracranial lesion?
8%
223
What's the detection rate of CT or MRI on spinal masses for feline lymphoma?
75% of extradural or intradural will be detected
224
Is CSF good for diagnosis of CNS lymphoma in cats?
yes it can be used
1/11 and 6/17 cats in 2 separate studies had neoplastic cells in CSF
225
What's the outcome of feline CNS lymphoma?
limited report
- <50% response
- MST 1-4m
RT can be used for local treatment with brisk response but adjuvant chemo should be considered
226
What are some common presenting signs of cutaneous lymphoma in cats?
- erythematous patches
- alopecia
- scaling
- dermal nodules
- ulcerative plaques
can be solitary or diffuse
227
Where are the most common places for feline cutaneous lymhoma?
head and neck
228
What's the most common immunophenotype of feine cutanoues lymphoma?
T cell
229
What's cutaneous lymphocytosis?
- uncommon form of feline LSA
- indolent, slowly progressive, but can eventually develop internal organ infiltration
- mostly T cell
- solitary lesion = most common
- histologically looks like well differentiated lymphoma
230
What's Sezary syndrome?
T cell cutaneous lymphoma with atypical circulating lymphocytes
231
Describe feline SQ lymphoma.
Rare presentation.
- SQ mass, with deeper tissue involvement and overlaying tissue without epitheliotropism
- most commonly found on the lateral thorax, lateral abdomen, intrascapular, and tarsal
- painless, firm
- central necrosis and peripheral inflammation
-2/3 = high grade B cell
- 1/3 = high grade T cell
- occasional NK cell
232
What's a differential for feline SQ lympoma?
FISS!
233
How often is feline SQ lymphoma localized?
the majority of them
- but one report of tarsal SQ lymphoma found 20% popliteal LN involvement
234
What's the outcome of feline SQ lymphoma?
50% of the cats with progress with local treatment
75% will eventually die due to LSA
- need both local and systemic therapy
- MST of 148d, 216d (tarsal with RT and chemo), 6m (chemo) reported (5m, 7m)
235
What's the outcome of feline laryngeal/pharyngeal LSA?
typically localized disease though 25% will have regional LN involvement.
- treatment with RT or CHOP/COP (90% CR)
- MST 5.5-9m, >1y also noted
236
What's the presentation of ocular LSA in cats?
usually part of multicentric disease
- uveitis = most common
- can also have corneal ulceration, exophthalmos, chemosis
- iridal mass
- presumed solitary ocular lymphoma = rare in cats
237
What's the outcome of ocular lymphoma in cats?
with enucleation, MST of 6m to >4y reported
238
What are the thresholds for diagnosing ALL and CLL based on bone marrow aspirates in cats?
ALL: >30% blast cells
CLL: > 15% mature lymphocytes
239
How common in ALL and CLL in cats?
ALL was common in the FeLV era, mostly T cell
CLL is rare, also mostly T cell
240
What's the outcome of feline ALL?
27% CR to COP
disappointing outcome (<2m)
241
What are the 3 types of clonal disorders to the bone marrow?
1. myeloaplasia (aplasitic anemia)
2. myelodysplasia
3. myeloproliferation
242
What's myeloid leukemia and myeloproliferative disorders?
They are clonal proliferation of hematopoietic stem cells.
243
What's the usual behaviour of AML?
- acute myeloid leukemia
- rapidly progressive
- MST < 2m
- male:female 2:1
- need molecular diagnostics to figure out the exact lineage (granulocytic, monocytic, erythroid, or megakaryocytic)
244
What are some examples of myeloproliferative diseases?
1. polycythemia vera
2. essential thrombocytosis
3. chronic myelogenous leukemia (granulocytes/ monocytes)
245
What's are some differentials for meyloproliferative diseases?
none neoplastic ones! need to differentiate
246
Which hormones/ factors can stimulate production of the various hematopoietic cells?
1. Erythropoietin: produced by the kidneys, stimulates erythrocyte proliferation and differentiation
2. Colony stimulating factors: for granulocytes/ monocytes, can also influence the functional capabilities of the mature cells
3. Thrombopoietin: proliferation and stimulation of megakaryocytes
247
What's the definition of myelodysplastic disease?
- it's a pre-leukemic phase
- there is pancytopenia
- bone marrow hyperplasia and maturation arrest
- may not develop into leukemia
- can be seen in cats with FelV
248
What are some features of acute myeloid leukemia?
- uncontrolled proliferation
- decreased apoptosis
- accumulation of poorly differentiated "blast" cells
249
What are some features of chronic myeloid leukemia/ myeloproliferative neoplasm?
- unregulated proliferation
- progressive, incomplete, maturation
250
Define myelophthisis.
neoplastic cells displacing normal hematopoietic cells
251
Define aleukemic leukemia.
When there is neoplastic blast cells in the bone marrow but not in the periphery circulation.
252
Which organs can be involved in acute myeloid leukemia?
Lymph nodes = frequently involved
- others: tonsils, kidneys, heart, CNS
253
What are some common cytopenias and their sequelae with AML?
- anemia, thrombocytopenia, neutropenia
- infection and hemorrhage
- could be more fatal than the actual AML
254
What are the most common AML in dogs?
1. monocytic leukemia (M5)
2. myeloomonocytic (M4)
4. Myeloblastic without differentiation (M1)
5. Megakaryoblastsic (M7)
6. Myeloblastic with differentiation (M2)
7. Erythroeukemia (M6)
255
Which missense mutations have been identified in dogs with AML?
- flt-3
- kit
- ras
256
Which chromosomal translocation is found in dogs with acute myeloblastic leukemia?
bcr-abl
257
Which mutation has been identified in dogs with polycythemia vera?
Jak2
258
Define myelofibrosis.
- proliferation of megakaryocytes and granulocytes precursors
- and accumulation of collagen
- primary disease = rare, more likely due to insult/ injury to the marrow
259
Describe polycythemia vera.
- clonal disorder of a stem cell (not sure if it's the pluripotent or multipotent)
- leading to proliferation of erythrocytes with terminally differentiated RBC
- increased RBC mass, PCV, and hemoglobin
- PCV ~ 65-85%
- other cell lines typically not affected (unlike people)
- 1 in 5 dogs have Jak2 mutation (vs. 90% of people)
260
What's the Raleigh chromosome?
Chromosome 9 and 26 (bcr-abl)
Implicated in canine chronic myelogenous leukemia
261
What are some features of canine myelogenous leukemia?
- neutrophilia (both mature and immature)
- total WBC usually >10k
- erythroid and megakaryocytes can be effected --> anemia, thrombocytopenia (less commonly thrombocytosis)
- need to differentiate from "leukemoid reactions" from inflammation or immune-mediated disorders
- can also be a paraneoplastic syndrome
262
What's the cause of death in CML?
- hemorrhage
- infection (dysfunctional neutrophils)
- "blast crisis" is also possible
263
Which other organs can also have CML involvement?
- red pulp of spleen
- periportal and sinusoidal areas of the liver, some times LNs
- can also have extramedullary hematopoiesis in liver and spleen
264
What are some differentials for eosinophilic leukemia?
parasitism
skin disease
GI or respiratory diseases
- need to confirm clonality for neoplasia
265
What define essential thrombocytosis?
- Platelet count > 600K
- no blast cells in circulation
- marked megakaryocytic hyperplasia without collagen accumulation
266
What are some differentials for thrombocytosis?
- iron deficiency anemia
- inflammation
- rebound ITP
- splenectomy
- hemolytic anemia
- recovery from severe hemorrhage
- cancer
- vincristine/ drug induced
267
What are some PE findings for essential thrombocytosis?
- GI bleeding
- splenomegaly
- increased numbers of basophils
- spurious microcytosis if large platelet are counted as small RBCs
268
what are some consistent features of myelofibrosis?
- anemia
- thrombocytopenia
- splenomegaly
- myeloid metaplasia (production of hematopoietic cells outside of the bone marrow)
269
What are some causes of myelofibrosis in dogs?
- radiation
- other myeloproliferative diseases
- infection (erlichia), septicemia
- drug toxicity (estrogen, cephalosporins)
270
What's myelodysplastic syndrome?
Rare
- usually has cytopenia in 2+ lines
- bone marrow = normocellular or hypercellular
- dysplastic changes in several cell ines
- blast cells typically <30% (new threshold = <20%)
271
What are some poor prognostic factors for myelodysplastic syndromes?
- >1 cell line affected
- increased % of blast cells
- cellular atypia
272
Define the following:
-MDS with excessive blasts
- MDS with refractory cytopenia
- MDS with erythroid predominance
1. MDS-EB: blasts 5-20%
2. MDS-RC: blasts <5%, 1+ cytopenia
3. MDS-ER: M:E ration <1, poor prognosis
273
Whare are some common presenting signs for dogs with leukemia?
- lethargy
- pallor
- anorexia
- weight loss
- persistent fever
- petechia
274
How often if peripheral lymphadenopathy and hepatosplenomegaly in dogs with leukemia?
40-75% will have peripheral lymphadenopathy
40% will have hepatosplenomegaly
275
What are some common signs of myeloid dysplastic syndrome?
- lethargy
- anorexia
- pallor
- fever
- hepatosplenomegaly
276
What are some common signs with polycythemia vera?
- erythema of the mucus membranes
- neurological signs: disorientation, seizure, ataxia (due to hyperviscosity or hypovolemia)
- usually no hepatosplenomegaly
277
What type of anemia is common with leukemia? with myelofibrosis?
nonregenerative normocytic normochromic
- most severe in AML
in myelofibrosis:
- anisocytosis and poikilocytosis
278
What's the cell morphology for blasts in myelomonocytic leukemia?
pleomorphic nuclei
279
What's the cell morphology in megakaryocytic leukemia?
blasts have vacuolation and cytoplasmic blebs
280
Which stains can be used for neutrophilic differentiation?
if blasts stain positive for:
- peroxidase
- Sudan black B
- chloracetate esterase
281
What stains would indicate monocytes?
nonspecific esterase inhibited by sodium fluoride = monocytes
282
Which marker can be used for megakaryocyts?
acetylcholinesterase
- von Willebrand's factor (factor VIII) and platelet glycoprotein also helps
283
What's the utility of ALP staining for AML?
ALP can stain blast cells in acute myeloblastic and myelomonocytic leukemia
- but it also stains positive for lymphoid leukemia
284
What's the bone marrow differential count for diagnosis of acute myeloid leukemia?
- erythrocytes < 50%
- > 20% blast cells
285
What's the bone marrow differential count for diagnosis of M6 or M6-Er?
M6 = erythroid leukemia
- >50% erythrocytes
- > 20% blasts
M6-er
- if there is also rubriblast presence
286
Which marker in flow cytometry can help with the diagnosis of AML?
- all AML and ALL will be CD34+
- then rule out ALL: CD3, CD79a, CD4, CD8, CD21 and IgG
- myeloperoxidase (MPO) and CD11b = myeloid cells
- CD 41 for megakaryoblasts
287
Which is the common constellation of CD markers for canine AML?
CD34, CD45, and CD18
288
What marker can be used for:
- B cell
- T cell
- myeloid cells
- megakaryocytes
- dendritic cells
- acute leukemias
- B cell = CD79a
- T cell = CD3
- myeloid cells = myeloperoxidase, CD11b
- megakaryocytes = CD41
- dendritic cells = CD1c
- acute leukemias = CD 34
289
What is one way to diagnose CML?
biopsy of the liver or spleen to differentiate from leukemoid reaction
290
How can basophils and mast cells be differenitated?
basophil nucleus = more ribbon like; mast cell = round/ oval
basophils have variably sized granules; mast cells with lots of small round metachromatic granules
291
How is essential thrombocytosis diagnosed?
- persistently >600k platelets without blasts
- ruling out secondary thrombocytosis
- no other myeloid proliferative disease
292
How do the platelets look in essential thrombocytosis?
may have giant forms and abnormal granulation
293
Why would some patients with essential thrombocytosis have elevated serum potassium?
due to release of potassium from platelets from clot formation
- check plasma potassium - it would be normal
294
What are some typical features of myeloid dysplastic syndrome?
2+ cell lines affected: neutropenia +/- L shift, non-regenerative
anemia, thrombocytopenia
- the bone marrow typically has <20% blast cells, normal or hypercellular
295
What are some signs that would be suspicious for myelofibrosis?
- non-regenerative anemia or pancytopenia
- abnormal RBC morphology, especially shape
- leukoerythroblastosis
296
How is myelofibrosis diagnosed?
- bone marrow aspirate may result in "dry tap"
- so a bone marrow biopsy may be needed
- also need to find the primary cause!
297
How is AML treated?
no standard of care
- Ara-C slow infusion daily x 3d, weekly or SQ injections
- CHOP or COP based protocols
- RR 50-70%
but MST = 0.5-m
298
What's the prognosis with supportive care only?
- even with treatment, intensive supportive care is usually needed to combat the cytopenia
- ex. transfusion of whole blood or platelet-rich plasma
- aggressive antibiotic therapy
- MST with supportive care only = 1-2 weeks
299
What's the treatment goal of polycythemia vera?
To have PCV as close as normal as possible
- aim for a PCV of 50-60%, or reduce by 1/6 of its starting value
300
How is polycythemia vera treated?
Phlebotomy --> can safely remove 20ml/kg of blood on regular basis (need to replace the volume with colloid or crystalloid solutions)
- hydroxyurea: 30mg/kg PO daily x 10d then 15mg/kg PO daily
- JAK2 inhibitors may work for 1 in 5 dogs with the JAK2 mutation --> maybe Apoquel?
301
What' the treatment option for CML with bcr-abl mutation?
Imatinib (that's what's used in humans)
can also try toceranib
can enjoy months of remission
302
What chemotherapy can be used for treatment of CML?
Hydroxyurea
- 20-25mg/kg PO BID until leukocyte count falls to 15-20K, then reduce the dose by 50% daily, or use 50mg/kg PO 2-3 times a week
303
What's the outcome of CML?
can be controlled for months, but will eventually end in blast crisis --> poor prognosis despite rescue with more aggressive protocols
304
What's the treatment for essential thrombocytosis?
- hydroxyurea
- combination of ara-C, vincristine, cyclophosphamide, and prednisone
305
How is myelodysplastic syndrome treated?
In people, it's only treated if there are clinical signs/ significant cytopenia
- supportive therapy
- growth factors
306
What is myeloma related disorders?
- plasma cell or immunoglobulin producing B cells
- typically monoclonal (though bi and polyclonal do exist)
- it's a spectrum of diseases: MM, Waldenstrom, EOP, SOP, plasmacytosis
307
What's the general outcome of multiple myeloma in dogs?
- >80% of dogs will response to therapy (melphalan, prednisone)
- MST = 1.5-2y
308
What' the general outcome of myeloma related diseases in cats?
- 50-80% will respond
- cyclophosphamide and prednisone
- MST 4-13m
309
How is multiple myeloma diagnosed?
- plasma cell infiltration in the bone marrow or organ
- osseous lesions
- M component in serum or urine
310
What are some pathology related to multiple myeloma?
- bone lesion
- cardiac disease
- hyperviscosity syndrome
- hypercalcemia
- renal disease
- infection
- bleeding diathesis
- cytopenia secondary to myelophthisis
311
Which is the most common M component in dogs with multiple myeloma?
IgA and IgG
IgM = Waldenstrom's macroglobulinemia
312
Which M component is most common in feline multiple myeloma?
IgG > IgA
313
What kind of osseous lesions can be seen in multiple myeloma?
can be discrete, diffuse, osteopenic, osteolytic, or all
314
How often is radiographic evidence of bone lesions noted in dogs with multiple myeloma?
25-66%
315
How often is radiographic evidence of bone lesions noted in cats with multiple myeloma?
quite variable - reports as low as 8% to as high as 65%
316
Which bones are more likely to be affected with multiple myeloma?
Those that are engaged in active hematopoiesis:
vertebrae, ribs, pelvis, skull, and metaphases of long bones
317
How common is bone lesions with Waldenstrom?
not common
more likely to have spleen, liver, and lymphoid tissue infiltration than bone
318
What are the 4 ways that MM can lead to coagulopathy?
1. decrease platelet aggregation and release of platelet factor 3
2. decrease calcium
3. adsorption of minor clotting proteins
4. abnormal fibrin polymerization
319
How often is clinical hemorrhage noted in dogs and cats with multiple myeloma?
10-30% of dogs
25% of cats
320
How often do dogs with MM have PT/PTT prolongation?
50%
321
322
What's hyperviscosity syndrome?
caused by sludging of the blood, resulting in inadequate delivery of oxygen and nutrition, as well as coagulopathy
323
What are some signs of hyperviscosity syndrome?
- bleeding diathesis
- neurological signs (seizures, abnormal mentation, coma)
- ocular signs (retinal hemorrhage, retinal detachment, dilated tortuous vessels)
- increased cardiac workload --> DCM
324
How common in hyperviscosity syndrome?
Depends on the M component as well
- IgM = big = very likely
- IgA dimerizes in dogs, so also more likely
in dogs: 20-40%
325
How common is renal disease in dogs and cats with multiple myeloma?
Dogs: 25-50%
Cats: 30-40% will have azotemia
326
What are some causes of renal disease with multiple myeloma?
- Bence Jones protein --> can precipitate in urine leading to glomerular damage
- tumour infiltration
- hypercalcemia
- secondary to hyperviscocity syndrome
- dehydration
327
How common is Bence Jones proteinuria in dogs and cats?
Dogs: 25-40%
Cats: 40%
328
How often in hypercalcemia in dogs and cats with multiple myeloma?
Dogs: 15-50%
Cats: 10-25%
329
How frequent is thrombocytopenia and leukopenia in dogs with multiple myeloma?
thrombocytopenia = 30%
leukopenia = 80%
330
What are the most common presenting signs for multiple myeloma in dogs and cats?
Cats:
- weakness and lethargy
- anorexia
- pallor
Dogs:
- weakness and lethargy
- inapppetance and weight loss
- lameness
331
What's the minimum plasmacytosis for diagnosis of MM in the bone marrow?
dogs: 20%
cats: 10%
332
How useful is AUS for cats with multiple myeloma?
one study found 85% of abnormalities found on AUS were related to MM!
- splenomegaly, hepatomegaly, renomegaly, iliac LN enlargement
333
How useful is nuclear scintigraphy for detection of bony lesions?
Not very useful
- most MM lesions are osteolytic rather than osteoblastic, bone scans seldom give positive results
334
What are some differentials for MM?
- B cell LSA
- extramedullary plasmacytoma
- chronic or acute B cell leukemia
- infections (Ehrlichiosis, leishmania, FIP)
- monoclonal gammopathy of unknown significance
335
What's the treatment for multiple myeloma?
Melphalan!
- 0.1mg/kg PO daily x 10d then 0.05mg/kg PO thereafter
- or, 7mg/m2 PO daily x 5d every 3 weeks
- RR = 72-94%
336
What's the steroid regiment for multiple myeloma?
steroids can enhance the activity of melphalan
- 0.5mg/kg PO daily x 10d
- then 0.5mg/kg PO EOD thereafter
- consider discontinue after 60d
337
How long is the melphalan protocol for multiple myeloma?
Lifetime as long as the MM is controlled and there is no toxicity to the melphalan.
- cumulative thrombocytopenia
- need to do CBC every 2 weeks in the first 2m
- then at least monthly or before every pulse dosing
- if significant bone marrow suppression is noted --> drug holiday --> reintroduce at a lower dose
338
How is multiple myeloma treated in cats?
melphalan and prednisolone may be too myelosuppressive in cats
- can use cyclophosphamide instead (250mg/m2 q2-3 weeks)
- if still using melphalan, 0.1mg/kg PO daily x 10-14d, then EOD
- or 0.1mg/kg PO once a week maintenance
- or 25mg/ per cat twice a week
- or 2mg/m2 every 4 d
339
When should cyclophosphamide be started at the same time as melphalan for dogs with MM?
- severe hypercalcemia
- widespread systemic spread needing a quicker acting alkylator
- give 250mg/m2 with the first dose of melphalan
- can also be used if thrombocytopenia develops
340
Chlorambucil has been used in which type of MM in dogs?
IgM
- 0.2mg/kg PO daily
341
What's the response of lomustine for cats with MM?
PR @ 50mg/m2 PO q3w
342
How long does it take to see response to therapy for dogs with MM?
- subjective improvement in clinical signs = 3-4 weeks
- objective improvement in lab results (globulin/ M component, Ca, CBC) = 3-6 weeks
343
How long does it take to see response to therapy for cats with MM?
within 2-4 weeks for subjective improvement; 8 weeks for serum protein and radiographic bony lesions
344
What's the treatment goal for MM?
complete resolution of hyperglobulinemia generally doesn't occur
- good if it's <50% of pre-treatment value
- it will take some lag time for serum globulin to decrease after the Bence Jones proteins due to long half-life
- recheck chem monthly, and once good control is achieved, every 2-3m
345
How quickly can modest hypercalcemia improve with melphalan and prednisone?
within 2-3 days
346
What's a good short term treatment for hyperviscosity syndrome?
plasmapheresis
347
Is prophylactic antibiotics recommended for MM?
no, just treat aggressively if infection develops
- use bactericidal drugs and avoid the ones that can cause nephrotoxicity
348
What's an alternative treatment for MM?
rabacfosadine
MPFI = 172d (~6m)
349
Generally how do dogs respond to rescue protocol for MM?
initial good response, but durability of control is short
350
What's the general response to melphalan and prednisone in dogs with MM?
43% CR
49% PR
only 8% didn't respond
MST= 1.5-2y
351
What are some potential prognostic factors for MM in dogs?
- hypercalcemia
- Bence Jones proteinuria
- bone lysis
- renal disease
- lymphocyte:neutrophil ratio
352
What's the general prognosis for cats with MM?
not as good as dogs
- RR is lower @ 50-83%
- MST 4-13m
353
What's the outcome of IgM macroglobulinemia in dogs?
limited data, when using chlorambucil, 77% remission, MST = 11m
354
Where is extramedullary plasmacytoma most commonly found in the dog?
1. cutaneous (esp on the limbs and head)
2. oral
3. GI tract
355
What's the natural behaviour of non-cutaneous/non-oral extramedullary plasmacytoma?
tend to be more aggressive - can have associated LN involvement.
but colorectal EMP seem to have less biological aggressive
356
What's the natural behaviour of solitary osseous plasmacytoma?
most will eventually progress to multiple myeloma, but disease progression can take months to years
357
How often is cutaneous plasmacytoma part of systemic multiple myeloma?
95% of EMP = solitary, and <1% is part of the MM.
358
Is intravascular tumour cells in plasmacytoma a poor prognostic factors?
no, in one study, 16% of EMP had tumour cells in the blood vessels
359
What's the risk of LN + abdominal viscera involvement for cutaneous plasmacytosis?
30%
none had bone marrow involvement
360
How is cutaneous or oral EMP treated?
usually curative with conservative therapy as they are almost always benign
361
How is cutaneous plasmacytosis treated?
With systemic therapy and prednisone
- melphalan RR = 74%
- lomustine RR = 71%
- PFI - 153d (~5m)
- MST 542 d (~ 1.5y)
362
What's the role of RT in solitary osseous plasmacytoma?
can be used with surgery or alone, for palliative or curative intent.
Sr-90 has been sused for lingual plasmacytoma in the dog.
MST ~ 2.5y (3y if completed the RT) - mostly in vertebrae
363
How do cats with SOP respond to treatment?
1 cat was treated with RT and another treated with melphalan, both lived >4y
364
What' the local recurrence rate, new tumour growth, and metastatic rate for dogs with cutaneous EMP?
5% recurrence rate
<2% for new masses
2% with LN or distant spread
365
Which histology parameter may have a role in prognosis of EMP?
-polymophous-blastic and plasmablastic may be more aggressive
- proliferation indices (ex. ki67), intravascular tumour cells/ emboli, and histological grading = not prognostic
366
What's the MST of colorectal EMP?
15m with surgery only
367
What's the outcome of RT for plasma cell tumours in dogs?
Good, they are radiosensitive: 86% RR
- for non-MM, MST - 771ays (2.1y)
- for MST for all dogs = 697d (1.9y)
Elliot et al 2020
368
What's the RR and outcome of canine multicentric LSA treated with lomustine and prednisolone as first line?
RR = 87% (CR 15/30: 8 T cell, 4 B cell); not statistically different
MST = 3m
(Catalucci et al 2024)
369
The describe the biological behaviur of canine granular lymphocyte LSA.
in a Yale et al 2024 with 65 dogs
- most common c/s = lethargy and hyporexia
- most common anatomical form = hepatosplenic, and GI
- 30% had peripheral blood/ bone marrow involvement
- treatment with MTD chemo
- 74% RR but MST only 28d; 6 had long term ST, MST of 198d
- negative prognostic factors = monocytosis and peripheral blood involvement
- intermediate cell size = better
370
What's the outcome of cats diagnosed with myeloid related disorder?
- most cats have splenic or hepatic involvement, just over half have bone marrow involvement
- overall RR with prednisone and: Melphalan = 87%, cyclophosphamide = 90%, and chlorambucil = 100%
- anemia and thrombocytopenia = negative prognostic factor
- MST = 122d (4m)
- melphalan and cyclophosphamide MST = 315d (11m); less AE with cyclophosphamide vs melphalan
371
Does endogenous serum cortisol concentration influence outcome of dogs with LSA treated with chemotherapy?
Yes!
PFS 136d vs 180d (4.5m vs 6)
MST = 96d vs 180d (3 vs 6m)
Although no significant differences were found in the rate of P-gp-positive cells between the 2 groups, the rate of GCR-positive cells was significantly lower in the high COR group
372
What's the outcome of cast with high grade and large granular alimentary LSA treated with CHOP or COP?
RR = 42% (20% CR, 22% PR)
- MST = 131d (4m)
- if achieving CR = 203d (~7m)
Bernardo et al 2024
373
What's the outcome of cats with cutaneous/ SQ hemangiosarcoma and lymphamgiosarcoma treated with surgery +/- chemo/ Palladia?
HSA = 166d (factor VIII positive, PROX-1 negative)
LAS = 197d (both factor VIII and PROX-1 positive)
- difficult to remove completely
- local recurrence is high (60%)
374
What are some prognostic factors for canine T cell nodal LSA receiving alkylators?
if bone marrow involvement > 5%, MST = 114d (4m)
vs if <5%, MST = 178d (6m)
375
Is mesenteric LN biopsy appropriate for small intestinal LSA in cats?
- 43% had nodal infiltration
- clonality results correctly identified 63% of the LNs as reactive (ie. counted the remaining 37% of reactive LNs as neoplastic).
376
What's the outcome of cats with intermediate/large cell LSA treated with CMOP (mitoxantrone)?
- RR = 74%
- PFI = 139d (~4,5m)
- MST = 206d (~7m)
- if achieved CR, 2y survival rates = 57%
Webster et al 2024
377
What's the outcome of pegylated Elspar for cats with large cell LSA?
- RR = 74%, 38% CR
- PFI = 70d
- MST = 79d
IM elspar injection
Bik et al 2023
378
What's the outcome of dogs treated with MVPP for resistant LSA?
mechlorethamine, vinblastine, procarbazine, and prednisone
- RR = 25%
- PFI = 15d
- MST = 45d
Zimmerman et al 2023
379
What's the outcome of 10-day cyclic melphalan cycle for canine multiple myeloma?
10 days of melphalan @ 2mg/m2/day, with 10day break. Each cycle = 20 days
- RR= 76% (CR = 59%, PR = 18%)
- MST = 512d (1.4y)
Teddy et al 2023
380
Which needle gauge would be most appropriate for FNA of the canine spleen?
tested 23G, 25G, and 27G
- 23G had higher cellularity than 27G
- pain was low in all 3, but lowest in 27G
- would recommend 23G due to better cellularity and low pain
Launay et al 2023
381
What's the outcome of cats with tracheal LSA treated with chemo?
MST = 214d (7m)
382
Which tumours can be positive for MUM-1?
typically used for plasma cell tumours, but histiocytic and LSA can also be positive
383
What's the outcome of dogs with MDS/AML treated with doxorubicin/ cytarabine combination?
Doxorubicin @ 30mg/m2 with cytarabine @ 300mg/m2 CRI over 4h, once every 2-3 weeks for 4-6 cycles
MST = 369d
median duration of remission for responders = 344d
Matsuyama et la 2023
384
What histological features are associated with poor prognosis in canine cutaneous T cell LSA?
- extensive infiltration of the panniculus
- MC ≥7/high-power field
- cell diameter ≥10.0 µm
- nuclear diameter ≥8.3 µm
Dettwiler e al 2023
385
What can be seen on MRI for intravascular lymphoma in dogs?
ischemia and hemorrhagic lesions
Mattei et al 2023
386
What dose intensity associated with ST in dogs with T cell LSA treated with CHOP-based protocols?
No
PFI= 91d (3m)
MST = 196d (~6m)
Lenz et al 2023
387
What was one feature in oral EMP in dogs that may lead to an increased risk of systemic progression?
MC >28/10 hpf
- most oral EMP had long MST = 973d (2.7y)
- but 1/3 did have progression with 2 --> multiple myeloma
Evenhuis et al 2023
388
What's the outcome of feline tracheal/laryngeal LSA?
26% had surgery
all received chemotherapy
- MST = 909d (2.5y)
- most common presenting signs = increased respiratory effort and upper respiratory tract sounds
- the majority are B cells
Rodriguez-Piza et al 2023
389
What's the outcome of low dose HBI as consolidation for dogs with multicentric LSA in CR after CHOP?
With HBI:
2y disease free rate = 56%, survival = 78%
Without HBI:
2y disease free rate = 0%, survival = 11%
Best et al 2023
390
How much can drugs be escalated in a 15w CHOP protocol?
Vincristine was successfully escalated to 0.8 mg/m(2) or higher in 11 dogs, cyclophosphamide to 300 mg/m(2) or higher in 16 dogs, and doxorubicin to 35 mg/m(2) or 1.4 mg/kg or higher in 9 dogs.
RR = 100%
PFI = 171d (~6m)
MST = 254d (8.5m)
Siewert et al 2023
391
What's the most common etiology for cats with eosinophilic pleural effusion?
neoplasia (ex. LSA)
Wheatley et al 2023
392
What's the outcome of cats <18m treated for lymphoma?
- most common form = mediastinal
- CR = 46%, PR = 50% with chemotherapy
- PFF = 133d (4m)
- MST = 268d (9m)
- 7 cats lived > 2y
Regato et al 2023
393
What's the outcome of canine nodal small cell B cell LSA?
- median PFS = 119d (4m)
- MST = 222d (~7m)
- factors associated with shorter OS: low MHC II, high CD25, low Cd21, greater age, and substage B
Rout et al 2023
394
What's the significance of baseline serum C reactive protein for dogs with diffuse large B cell LSA?
lower = longer ST
<1mg/dL, MST = 315d (10m)
>1mg/dL, MST = 232d (8m)
Childress et al 2022
395
What's the outcome of cats with nasal/ nasopharyngeal LSA treated with SBRT?
MST = 365d
PFI = 225d
negative prognostic factors = cribriform plate invasion and intracalvarial invasion
Reczynaska, et al 2022
396
What's the MST of retrobulbar LSA in cats?
MST = 85d
397
What's the outcome difference in cats with nasal LSA receiving PRT as first line vs receiving PRT after chemo failure?
PRT alone: ~ 1y
PFS = 336d
MST = 346d
PRT after chemo failure: 7-8m
PFS = 228d
MST = 242d
Yamazaki et al 2022
398
What's the RR to rabacfosadine for canine LSA?
73%: 50% CR, 23% PR
Weishaar et al 2022
399
What the accuracy of LN FNA for canine LSA?
Generally good, but not for further characterization of the LSA:
- >60% for low grade T-cell lymphomas,
- <40% for low grade B-cell lymphomas
- >30% for high grade B-cell lymphomas
- >20% for high grade T-cell lymphomas.
Martini et al 2022
400
What's the RR of cyclophosphamide with prednisone as an induction to treatment naive B cell LSA in dogs?
RR: 84% - 62% PR, 9% CR
side effects in 47% of patients
Todd et al 2022
401
What's the importance of serum amyloid A in feline nasal LSA?
Serum amyloid A is significantly higher in non-nasal LSA compared to nasal LSA, but it's not prognostic for LSA
- prognostic factors = no response to treatment and low HCT
Schiavo et al 2022
402
What's the proportion of B cell CLL with monoclonal gammopathy?
M-protein was detected in 67%
Hyperproteinemia found in 35%
IgM = most common isolate
Harris et al 2022
403
404
What's the RR for single pegylated Elspar injection for cats with LSA and those that continue on with COP?
Single pegylated Elsapr:
RR = 82%, CR in 38%
- 34/56 continued with COP
- 92% achieved CR
- PFI = 816d with CR (2.2y)
- OST = 181d (6m)
405
In a dose finding study for pegylated Elspar in healthy beagle dogs, which doses resulted in antibody developlment?
20 and 40 IU/kg (found in 5 dogs)
at 10 IU/kg there is evidence of asparagine depletion lasting 9-29d
(Feensra et al, 2022)
406
Can prednisolone pre-treatment affect sensitivity to doxorubicin and vincristine in cats?
Yes, according to cell line studies
Hlavaty et al 2021
407
407
What's the outcome of diffuse small cell B cell LSA in dogs?
it's not indolent!
MST = 140d (~5m)
Hughes et al 2021
408
What's the utility of serum haptoglobin concentration in feline GI disease?
it can be useful to distinguish between normal and those with GI disease; but cannot distinguish between GI disease and LSA.
Love et al, 2021
409
What's the outcome of using cyclophosphamide as a rescue after chlorambucil for cats with small cell GI LSA?
good!
CR in 90%
median PFS = 215d (7m)
Kim et al 2021
410
What's the outcome of renal LSA in cats treated with prednisolone vs chemo?
Pred, MST = 50d
L-CHOP based, MST = 203d (~7m)
Not prognostic:
therapy administered, renal LSA vs multicentric LSA , CNS involvement, presence of azotemia, anemia and IRIS stage
Williams et al 2021
411
Is monoclonality an exclusive feature of small cell GI LSA?
NO!
70% of LPE had monoclonality (vs. 100% in LSA)
- LPE also has marked fibrosis in the lamina propria (94%)
- LSA had in-depth mucosal infiltration (68%)
Freiche et al 2021
412
What are some negative prognostic factors for canine chronic B cell leukemia?
generally B cell CLL is not as good - MST = 300d (10m)
Negative prognostic factors include:
- Boxer (178 vs 423d)
- high lymphocyte count >60K
- high Ki67 (>40%) (MST = 173d)
- symptomatic
Rout et al 2021
413
What's the outcome of a novel LOPH protocol for feline high grade multicentric or mediastinal LSA?
Lomustine, vinc (IP), doxorubicin, and vinc (IP)
CR = 81%
MST = 214d (7m) for mediastinal, not reached for multicentric
for FeLV (+) = 171d (~6m)
414
What's the outcome of feline high grade LSA rescued with methotrexate, lomustine, and cytarabine?
RR = 46%
MPFI = 61d (2m)
- 2 cats with grade III anemia and 1 cat with grade III thrombocytopenia
Smallwood et al 2021
415
What are some features that can distinguish between feline nasal LSA and adenocarcinoma based on MRI?
- adenocarcinoma has higher apparent diffusion coefficient values compared to lymphoma
Tanaka et al 2021
416
What are some risk factors for creatinine elevation in cats receiving doxorubicin?
- more likely with single agent vs CHOP
- anemia, neutropenia and number of RT under GA = risk factors
417
What are some prognostic factors for canine B cell LSA?
- CD25+: increased expression = decreased ST
- RR = 96% for DLBCL, with MPFS = 233d, MST = 325d (~11m)
- RR = 60% for nodal marginal zone LSA
- RR = 67% for small cell B cell LSA
Wolf-Ringwall et al 2020
418
What's the outcome of CD4-/CD8- and CD8+ nodal T cell LSA in dogs?
CD4-/CD8- MST = 145d (~5m)
CD8+ MST = 198 (~6.5m)
- hypercalcemia and mediastinal mass more likely to be CD4-/CD8-
Harris et al 2020
419
Describe the IHC expression of English bulldog non-neoplastic lymphocytosis.
- polyclonal
- B cell
- low MHCII and CD25 expression
- splenomegaly
- hyperglobulinemia (IgA +/- IgM)
- mostly male (74%), young (6.8y)
Rout et al 2020
420
What's the outcome for rabacfosadine + Elspar for relapsed LSA?
Elspar given with the first 2 doses of Tanovea
RR= 67%, 41% CR
- MPFS = 63d (2m)
- MPFS = 144d (4.5m) if CR
- negative prognostic factors: no CR or previous Elspar use
Cawley et al 2020
Compared to Saba et al 2018 paper (just B cell):
- RR = 74%, 45% CR (73.3%; 50%)
- MPFI = 108d (63)
- MPFI = 203d if CR
421
How reliable is mass spectrometry for differentiating LPE and small cell GI LSA in cats?
relative sensitivity, specificity, and accuracy of 86.7%, 91.7%, and 88.9%, respectively, compared to clonality testing, which had sensitivity, specificity, and accuracy of 85.7%, 33.3%, and 61.5%
Marsilio et al 2020
422
How does the immunophenotype of feline lymphocytosis affect the outcome?
MST:
CD4+ = 752d (2y)
CD4-/CD8- = 271d (9m)
CD5 low = 27.5d (4w)
Rout et al 2020
423
What are some CT features to differentiate between thymoma and mediastinal LSA in dogs?
- thymoma is more likely to have heterogenous attenuation
- lymphoma is more likely to wrap around the cranial vena cava
Reeve et al 2020
424
What's the significance of honeycomb spleen in cats on AUS?
- mostly benign!
- 16% = neoplastic: 3/4 = LSA, 1/4= carcinoma
Harel et al 2020
but in Quinci et al 2020, 24% of cats = LSA
425
What's the general outcome of Tanovea for naive canine multicentric LSA?
RR = 87% (CR = 52%, PR = 35%)
- MPFI = 122d (4m)
- most common AE = GI
- grade 5 pulmonary fibrosis in 3/63 (4.7%)
- pre-treatment with steroids and T cell = negative prognostic factor
- T cell RR = 50%, (22% CR) vs B cell RR = 97% (62% CR)
Saba et al 2020
426
What are some flow cytometry features for non-indolent T cell LSA that influences the survival?
RR = 80%
but MFPI = 105d (3m) with MST of 136d (4m)
- negative prognostic factors: CD3-/CD79a, anemia, and thrombocytopenia = shorter OST
Purzycka et al 2020
427
What's the response of MOPP (mustargen, vinc/vinb, procarbazine, predniosolone) for relapsed/ resistant LSA in cats?
RR = 70%
median remission = 166d (5.5m)
- if CR, median remission = 190d
- most common AE = neutropenia and GI
- 15% in remission at 1y
Maloney Huss et al 2020
428
What's the clinical out come of primary bone marrow T cell LSA in dogs?
- the study looked at 11 dogs with hypercalcemia and they have T cell LSA in the bone marrow
- no evidence of LSA outside of the medulla
- MST = 260d (~9m)
Portanova et al 2024
429
What's the outcome of MOC (melphalan, vincristine, cytozar) for treatment of relapsed canine LSA?
RR = 38%, CR in 19%
MPFI = 29d
430
What's the difference in outcome for cats receiving hypofractionated RT alone or in combination with CHOP for nasal lymphoma?
RT + Chemo:
- PFI = 677d (1.9y)
- MST = 983d (2.6y)
RT only
- PFI = 104d (3.5m)
- MST = 263d (8.8m)
Goto et al 2022
431
Is neutrophilia a good or bad prognostic factor for dogs with LSA treated with CHOP?
- has shorter PFI and RR compared to those with normal neutrophil counts
- PFI: 70d vs 184.5d (2.5 vs 6m)
- RR: 75% vs. 97%
Veluvolu et al 2021
432
What's the MST of dogs with multicentric LSA treated with prednisone only?
50days
pred: 40mg/m2 PO x 7 d then 20mg/m2 PO thereafer
Rassnick et al 2021
433
What are some uncommon side effects with Elspar in dogs?
- uric acid crystalluria (Tvedten et al 2019)
-
434
Is a 12week CHOP-based protocol better than the CHOP-19?
No, even though it's more dose intense.
12week:
- PFS = 141d (3m)
- MST = 229d (7m)
19week:
- PFS = 245d (8m)
- MST = 346d (1y)
Vos et al 2019
435
What are some common bloodwork changes and what's the outcome for dogs with primary renal LSA?
Azotemia and erythrocytosis were common.
MPFI = 10d
MST = 12d
if responded to chemo, MPF = 41d, MST = 47d
Taylor et al 2019
436
What's the difference in outcome with hypercalcemic T cell LSA treated with L-CHOP vs MOPP?
median PFI:
133d (4m) for L-CHOP
97d (3m) for MOPP
Angeloa et al 2019
437
What's the outcome of RT for feline nasal LSA?
median PFI = 974d
MST = 922d
1/3 of cats developed systemic disease
Meier et al 2019
438
What are some radiographic features to distinguish between thymoma and mediastinal LSA?
If you can see at least 2 distinct margins on the laterals, then it's more likely to be thymoma than LSA
Oura et al 2019
