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Canine Lymphoma + Leukemia Flashcards

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1
Q

Gains of chromosomes __ and __ and loss of chromosome __ have been documented in canine lymphoma

A

Gains: 13, 31
Loss: 14

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2
Q

What chromosomal aberration has been associated with prognosis in dogs with lymphoma? Did it positively/negatively impact duration of first remission? ST?

A

trisomy of chromosome 13

Positively impacted duration of first remission and ST - dogs with trisomy had longer times

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3
Q

Somatic mutations in what genes (determined by exome sequencing) have been identified to overlap in several breeds in canine B cell lymphoma? What about T cell?

A

TRAF3-MAP3K14
FBXW7
POT1

T cell: none

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4
Q

What percentage of cats undergoing renal transplant developed cancer while on cyclosporine, and what percentage of those cases were lymphoma?

A

24% developed cancer (vs. 5.1% of control cats)

36% of those were lymphoma (0% of controls)

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5
Q

What percent of dogs with lymphoma present with multicentric lymphoma?

A

80%

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6
Q

What percent of dogs with lymphoma present with GI lymphoma?

A

5-7%

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7
Q

What breed has been documented to have lymhoplasmacytic IBD that progresses to GI lymphoma?

A

Basenji

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8
Q

GI lymphoma in dogs arises from T or B cells?

A

T cells and has epitheliotropism (new study, they used to think B cell)

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9
Q

What breeds may be overrepresented in cases of canine GI lymphoma?

A

Boxers
Shar Peis

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10
Q

What percent of canine lymphomas are medistainal?

A

5%

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11
Q

What percent of canine lymphomas are hypercalcemic?

A

10-40%

Most common with mediastinal (43% of hyperCa2+ lymphomas in one study)

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12
Q

Mediastinal lymphoma is most commonly B or T cell?

A

T cell

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13
Q

From what cells does canine epitheliotrophic lymphoma arise?

A

T cells - specifically more commonly CD8+ (humans CD4+)

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14
Q

Non epitheliotrophic lymphoma likes what layer of skin?

A

Middle and deep portions of dermis and subcutis

Spare the epidermis and papillary dermis

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15
Q

Hepatosplenic lymphoma is most commonly T cell or B cell?

A

T cell

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16
Q

What receptor do the T cells express in hepatoplenic lymphoma in dogs? Is it the same in people?

A

Gamma delta TCR

Same in humans

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17
Q

What percent of canine lymphomas are considered low grade?

A

5.3-29%

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18
Q

What breeds of dog are more likely to get B cell lymphoma?

A

Cockers
Dobies

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19
Q

What breeds of dog are most likely to get T cell lymphoma?

A

Boxers

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20
Q

Do goldens get more B or T cell lymphoma?

A

Equal - equal likelihood of both B and T cell

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21
Q

What percent of canine lymphomas are:
B cell
T cell
Mixed B and T cell
Null cell

A

B cell 60-80%
T cell 10-38%
Mixed 22%
Null <5%

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22
Q

In humans, MALT lymphomas are typically negative for what markers?

A

CD5
CD10

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23
Q

What percent of dogs with multicentric lymphoma have pulmonary infiltration on rads? Is it higher or lower using BAL?

A

27-34%

May be higher with BAL per Withrow (percentage not listed)

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24
Q

Most CNS lymphomas are B or T cell?

A

B cell

(Neuro chapter says B and T cell reported and doesn’t say one over the other)

T cell more likely to involve peripheral nerves

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25
Presumed solitary ocular lymphoma MST vs. peripheral lymphoma with ocular involvement?
PSOL = 769d Peripheral with ocular involvement = 103d
26
What percent of multicentric lymphomas have ocular involvement?
37%
27
What percent of uveitis was secondary to lymphoma?
17%
28
What is the most common paraneopalstic syndrome with lymphoma?
Anemia
29
What mediates paraneoplastic hyperCa in lymphoma?
PTHrP primarily Also: IL-1, TNF-alpha, TGF-beta, Vit D analogs
30
What percent of dogs with lymphoma are thrombocytopenic? Neutrophilic? Lymphocytosis?
Thrombocytopenia: 30-50% Neutrophilia: 25-40% Lymphocytosis: 20%
31
Monoclonal gammopathies happen in what percent of dogs with lymphoma?
6%
32
CSF was diagnostic for lymphoma in what percent of 27 samples in two studies?
74%
33
B cell markers
CD79a CD20 CD21 - can also be expressed in T zone lymphoma
34
T cell markers
CD3 - pan T CD4 - helper T CD8 - cytotoxic T
35
Sensitivity and false positive rate of colonality assays
Sensitivity 70-90% False positive rate 5%
36
>80% of dogs with multicentric lymphoma present at what stage
Stage III-IV
37
What percent of dogs with lymphoma had circulating cells and what percent of those dogs had actual bone marrow involvement?
28% had circulating cells 57% of those had true bone marrow involvement
38
What percent of dogs with lymphoma have abnormalities on CXR?
60-75% (27-34% of these are pulmonary infiltrates, 2/3 thoracic lymphadenopathy)
39
What lung pattern is typically seen with pulmonary infiltrates
Interstitial and/or alvealar Modular (rarely) and bronchial infiltrates can also occur
40
What percentage of dogs with lymphoma have cranial mediastinal lymphadenopathy?
20%
41
What percentage of dogs with lymphoma have abdominal LN, spleen, or liver involvement on AXR?
50%
42
Is cranial lymphadenopathy prognostic?
Yes -
43
MST without treatment for intermediate to high grade lymphoma?
4-6 weeks
44
CHOP-based chemo induces remission in what percentage of dogs with lymphoma?
80-95%
45
What is the MST overall for dogs treated with CHOP
10-12m
46
What percent of dogs are alive at 2y after treatment with CHOP
20-25%
47
What was the remission rate for dogs receiving dox + tanovea and what was the duration of remission
Remission Rate = 98% - similar to CHOP Remission duration = 6.5m
48
What is the expected CR with single agent dox and the anticipated MST
CR 50-75% MST 8m
49
PFS with dox+cytoxan+pred vs dox+pred for naive canine lymphoma
Dox+cytoxan+pred PFS = 8.2m Dox+pred PFS = 5.6m **Was not statistically significant
50
Median remission duration with single agent CCNU FOR FIRST LINE TX per withrow
40d - Sauerbrey JAVMA 2007
51
What percent should you decrease indicated drug by for MDR1 mut/mut patients
40-50%
52
How long does Withrow say a remission needs to be to use that protocol for reinduction?
Greater than or equal to 2m
53
Reinduction rates of nearly __ can be expected in dogs that have completed CHOP-based protocols and then relapse while not receiving chemo
80-90%
54
Overall response rates of __ are reported to rescue protocols with median response duration of __
Response rates: 40-90% Median response durations: 1.5-2.5m
55
What percent of dogs will experience longer rescue durations with rescue protocols
<20%
56
What is the response rate for CCNU+L-spar+pred in a RESCUE setting? Med duration of response? Med duration of CR?
Response rate: 77-87% (52-65% CR) Med response duration: 63-70d Med duration of CR: 90-111d
57
What was the response rate and % CR for Tanovea in a rescue setting for B cell lymphoma?
RR: 74% CR: 45%
58
What was the median response duration and median duration of CR for Tanovea in a rescue setting for B cell lymphoma?
Med response duration: 108d Med duration CR: 203d Saba VCO 2018
59
Rituximab targets what
CD20 Monoclonal antibody
60
Does rituximab work in dogs?
NO - it lacks external recognition of a similar antigen on canine lymphoma cells, and also is antigenic in dogs
61
What is the name of the canininzed mAb designed to target B cells in dogs? T cells?
B cells = blontuvetmab (Blontress) T cells = tamtuvetmab (Tactress) No longer available, they didn’t work
62
What are the response rates and median remission durations for cutaneous lymphoma treated with chemotherapy?
Response rate 40-80% Remission duration 3-6m
63
What factors have strong association as prognostic factors for lymphoma in dogs
Histopath/subclass - high grade unfavorable Immunophenotype T cell and low MHC II unfavorable WHO clinical substage - substage B unfavorable Genetic/gene expression analysis - some scores highly predictive of outcome Anatomic location - leukemia, diffuse cutaneous and alimentary, hepatosplenic forms unfavorable Anemia at presentation - unfavorable Steroid pretreatment - long pretreatment unfavorable Cranial mediastinal lymphadenopathy - unfavorable
64
What circulating biomarkers are prognostic indicators in dogs and is increased/decrease bad
Lactate dehydrogenase activity - increased is unfavorable Thymidine kinase activity - increased is unfavorable Haptoglobin - increased is unfavorable Serum VEGF - increased is unfavorable Glutathione-S-transferase - increased is unfavorable Hypercalcemia - unfavorable Serum cobalamin - decreased in unfavorable Serum albumin - decreased is unfavorable Serum C-reactive protein - variable, not really useful
65
What factors had modest association as negative prognostic indicators for canine lymphoma
WHO clinical stage - stage V unfavorable, stage I/II favorable Sex - females/neutered females unfavorable in the table but text says neutered females have better prognosis and males have higher incidence of T cell Neutrophilia - unfavorable Neutrophil:lymphocyte ratio - low is unfavorable Thrombocytopenia - unfavorable Lymphocyte:monocyte ratio - low is unfavorable Measures of proliferation - contradictory Chemo-induced hematologic toxicity - grade III or IV chemo induced neutorpenias may be favorable Geographic location - mixed, dogs in the west did worse than east and south in one study
66
Lower levels of what antigen and what receptor is associated with shorter survival
B5 antigen MHC II expression
67
Marginal zone lymphoma med PFI and overall ST
Med PFI = 5m overall ST = 8.5m **while it’s classified as indolent it’s generally more aggressive
68
Breeds overrepresented with CLL
GSDs and goldens
69
Small breed dogs are significantly more likely to get B or T cell CLL
B cell
70
What is the average age of onset for English bulldogs who get B-CLL
6y - this is younger than average, they get a different form
71
What proportion of CLLs are T vs. B cell
2/3 T cell 1/3 B cell
72
What three subtypes of CLL have been reported and what are their immunophenotypes
1. T-CLL - CD3+/CD8+ 2. B-CLL - CD21+ 3. Atypical CLL - many flavors - CD3-/CD8+ - CD3+/CD4-/CD8- - CD3+/CD4+/CD8+ - CD3+/CD21+
73
Immunophenotype for ALL of T cells is what
CD3+/CD4-/CD8-/CD21- **This is different from CLL b/c T-CLL is CD8+
74
What percent of dogs with B-CLL are reported to be hyperglobulinemic? Hypercalcemic?
Hyperglob = 80% Hypercalcemic = 13%
75
In a normal dog what percent of circulating lymphocytes are: T cells B cells NK cells
Normal dog: T cells = 80% B cells = 15% NK cells = 5%
76
In a normal dog’s circulating T cells are CD4 or CD8 more common
CD4 >>> CD8
77
Ddx for Lymphocytosis in dogs
Chronic ehrlichiosis Post-vx response in young dogs IL-2 administration Transient physiologic or epinephrine-induced Lymphocytosis
78
STs for CLL
1-3y
79
How long did it take for CLL to progress to acute disease in 8 dogs reported with Richter’s syndrome? What was the MST after progression?
2-16m MST after progression 41d despite aggressive chemo (CHOP) in half
80
What percent of CLLs will have normalization of lymphocyte counts with treatment?
70%
81
MST for 17 dogs treated with COP? Expected 2y survival?
MST 12m Expected 2y survival 30%
82
MSTs based on Immunophenotype for CLL
T-cell = 930d (31m) B-cell = 480d (16m) atypical CLL = 22d (<1m)
83
CLL with CD8+ phenotype: MST for <30k lymphocytes and >30k lymphocytes
<30k = 1098d (36.6m) >30k = 131d (4.3m)
84
Dogs with ALL treated with vincristine and pred - what percent reached CR or PR? What was MST?
CR + PR = 29% total MST = 120 (4m)
85
MST with CHOP for ALL with CD34+ phenotype
16d (range 3-128d)
86
B-cell ALL MST with CHOP
129d (4.3m)

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