LSA/Leukemia Flashcards
1
Q
Dogs with trisomy of chromosome ___ have a prognostic advantage in LSA.
A
13
2
Q
What lawn care product has been linked to LSA?
A
phenoxyacetic acid herbicides (particularly 2, 4-dichlorphenoxyactic acid; 2, 4-D)
3
Q
What % of cats undergoing renal transplant developed cancer? What % was lymphoma?
A
24%; 36% of those were LSA
4
Q
What % of dogs with LSA have hypercalcemia?
A
10-40%
5
Q
The mediastinal form of LSA occurs in ___%.
A
5%
6
Q
In a study of 37 dogs with LSA and hyperCa, what % had mediastinal LSA?
A
43%
7
Q
What LSA cells make up hepatosplenic LSA in humans and have been reported in dogs?
A
gamma-delta-T cells
8
Q
What % of high grade LSA are B-cell?
A
60-80%
9
Q
Diffuse pulmonary infiltration is seen in ___ to ___% of dogs with multicentric LSA.
A
27-34%
10
Q
Ocular involvement of LSA:
Up to ___ % have ocular changes consistent with LSA.
A
37%
11
Q
Other than PTHrp, what are some other mechanisms of hyperCa in LSA? (4)
A
IL-1, TNF-a, TGF-B, vit D analogs
12
Q
What percent of LSA dogs have lymphocytosis?
A
20%
13
Q
What % of LSA dogs have thrombocytopenia?
A
30-50%
14
Q
Conventional CHOP induces remission in ___ to ___% of dogs.
A
80-95%
15
Q
MST for conventional CHOP?
A
10-12 months per Withrow, recent Thamm presentation said 12-16 months.
16
Q
% of dogs that will be alive 2 years after initiation of CHOP?
A
20-25%
17
Q
CR for single agent DOX with pred? MST?
A
50-75%; MST 6-8 months
18
Q
What are three potential biomarkers of MRD?
A
serum lactate dehydrogenase, thymidine kinase 1, serum C-reactive protein
19
Q
What % of dogs will have successful reinduction with CHOP if they relapsed after completing a CHOP-based protocol?
A
nearly 80-90%
20
Q
What biomarkers have been associated with worse prognosis in canine LSA? (4)
A
lactate dehydrogenase, thymidine kinase, hypocobalaminemia, glutathione-S-transferase
21
Q
Does clonality testing help distinguish origin of AML?
A
No. Frequently were both B or T cell and some had biclonality. (Stokol 2017)
22
Q
In one report of 22 dogs with CLL, 68% had monoclonal gammopathies. What type of immunoglobulins?
A
Mostly IgM or IgA.
23
Q
What PE feature is common with ALL and may be seen in CLL?
A
splenomegaly
24
Q
Do Golden Retrievers have increased T-zone cells?
A
Yes (study evaluated dogs without LSA - 31% of older GR had T-zone cells vs. 14% non-GR; Hughes 2018)
25
What is most common form of peripheral T-cell LSA?
CD4+
26
What markers are characteristic of T-zone LSA?
CD45-, CD25+, MHCII high
27
What % of dogs with T-zone LSA have demodicosis?
10%
28
What is the normal distribution of T-cells, B-cells, and NK cells/double-negative T-cells in circulation?
80% T-cells (CD4+ outnumber CD8+)
15% B-cells
5% NK/double-negative
29
Which envelop protein is thought to be one of the mediators of immunosuppression in FeLV cats?
P15E
30
Per Withrow, what percentage of cats with non lymphoid hematopoietic neoplasia (myeloproliferative dz) test positive for FeLV?
70-90%
31
What % of cats with spinal, mediastinal, ocular, and renal LSA test positive for FeLV?
70%
32
The relative risk of developing LSA is ___ times higher in FeLV positive cats.
62
33
How does FeSV form?
Via recombination of FeLV DNA provirus with cat porto-oncogenes --> when FeLV-derived DNA inserts near a photo-oncogene and takes up the porto-oncogene into the FeLV provirus, formation of FeSV results.
34
Cats with FeSV always test positive on what viral antigen test?
FeLV
| tests p27
35
__% of fibrosarcomas in cats are viral induced.
2%
36
Metastasis to lungs or other organs occurs in approximately ___% of virally induced fibrosarcomas in cats.
30%
37
What is a missense mutation? Which missense mutations have been identified in canine acute myelogenous leukemia?
Missense mutation = nucleotide change that results in a different amino acid.
FLT3, c-KIT, RAS
38
Which gene mutation was reported in a dog with polycythemia vera that is similar to the human mutation in the same disease?
JAK2
39
What are the analogous chromosomes in dogs to the Philadelphia chromosome in people?
Philadelphia = BCR-ABL translocation btw chromosomes 9 and 22
Analogous in dogs = chromosomes 9 and 26 (Raleigh chromosome)
Associated with CML
40
What is seen in the peripheral blood in cats with FeLV myelodysplasia?
macrocytic erythrocytes; metarubricytosis
41
What is used to treat polycythemia vera?
hydroxyurea (inhibits DNA synthesis)
42
What disease in mink can lead to a monoclonal gammopathy?
Aleutian disease -- persistent infection of autonomous parvovirus
43
What is RR of feline intermediate/large cell GI LSA to CCNU? PFS? MST? (Rau 2017)
50% RR
PFS 132d
MST 108d
44
What factors significantly affected PFS in cats with intermediate/large cell GI LSA treated with CCNU? (Rau 2017)
Hx of hyporexia
Anemia
Dose of CCNU
45
Did dose intensification improve outcome for canine LSA?(Sorenmo 2010)
No, did not improve outcome. (note majority of dogs were stage 5b)
46
What was the incidence of toxicity with dose-intensified CHOP? Did toxicity affect outcome? (Sorenmo 2010)
53.9% toxicity (45% needed dose adjustment/delays)
| Yes, dogs with delays had longer TTP and MST.
47
How did BCS affect LSA survival? (Romano 2016)
Obesity did not affect survival, however being underweight (BCS <4/9) at time of dx was associated with shorter survival.
48
What is the RR of cats with LSA to DOX after failing COP?
22%
49
What is the RR of cats to L-spar?
30%
50
What is the MST with COP or CHOP for GI LGL in cats?
2 months (57d Krick 2008)
51
T/F: Transmural infiltration is common in feline low grade T cell GI LSA.
False
52
What % of cats with renal LSA develop CNS extension?
40-50%
53
T/F: Epitheliotropism is common in feline nasal LSA.
True
54
Which cells are characteristic of Hodkin's-like LSA in cats?
Reed-Sternberg cells (bizarre, multinucleated)
| Hodgkin's like is usually T cell rich, B cell LSA; FeLV negative
55
Which cat breed develops mediastinal LSA at a young age without being FeLV positive?
Siamese
56
What % of cats receiving renal transplants develop LSA?
10%
57
What is the relative risk of LSA in a cat with ETS exposure?
2. 4
| 3. 5 with 5 or more years of exposure
58
T/F: Feline small cell LSA is typically B cell.
False
59
Which form of canine CLL has the poorest prognosis?
Atypical (combo of phenotypes)
T cell: 930d, B cell 480d, Atypical 22d
60
What % of dogs with CLL will respond to tx with normalization of their lymph count?
70%
61
T/F: B cells are the most common circulating lymphs in normal dogs.
False
62
How does ocular involvement affect px in dogs with LSA?
Lifespan only 60-70% as long
| as compared to dogs without ocular involvement when treated with COP or DOX
63
What is the most common form of CLL in dogs?
CD8+ T-cell
64
What is the RR to CCNU in dogs with epitheliotropic cutaneous LSA? DFI?
80%
| DFI 3 months
65
What is the average latency period before sarcoma development following trauma to the feline orbit? What are two negative px factors?
5 years
| extension beyond sclera, extension into optic nerve
66
What doesn't rituximab work in dogs?
lack of external antigen recognition of a similar antigen on canine LSA cells
67
How does rituximab work?
chimeric murine/human mAb directed against CD20 (found on normal pre-B and mature B lymphocytes)
68
What is the RR for MOPP in rescue setting for dogs?
65%
| 31% CR
69
What is the RR to CCNU/Lspar/pred in rescue setting for dogs?
77-87%
| 52-65% CR
70
What is the RR to CCNU in rescue setting for dogs?
27%
| 7% CR
71
What is the RR to DMAC in the rescue setting for dogs?
72%
| 44% CR
72
What finding on CXR is negative px factor for canine LSA?
cranial mediastinal lymphadenopathy
73
What % of dogs with LSA have monoclonal gammopathy?
6%
74
What phenotype is hepatosplenic LSA?
gamma delta T-cell
| γδT-cells
75
What is the disease distribution of hepatosplenic LSA? (what organs are involved)
spleen, liver, BM
76
Which layer of the skin does non-epitheliotropic LSA affect?
middle and deep portions of the dermis/subcutis
77
Which chromosomal aberrations were most common in a group of 25 dogs with LSA?
gain of chromosomes 13 and 31
| loss of chromosome 14
78
Which is not seen with MDS?
1. blasts are >30% of all nucleated cells in BM
2. macrocytic erythrocytes
3. metarubricytosis
4. cytopenias in 2 or 3 lines in peripheral blood
5. normo- or hypercellular BM
1. blasts >30% of all nucleated cells in BM
| This is false, blasts are <30% per Withrow.
79
What gene mutation was reported in a dog with polycythemia vera that is similar to the human mutation?
JAK2
80
Which cell type stains for peroxidase, Sudan Black B, and chloreacetate esterase?
neutrophils
81
Which cells are positive for CD41?
megakaryocytic
| also CD9, CD61 - VCO 2012
82
What dx test can distinguish true leukemia from a leukemoid reaction?
liver/spleen biopsy
83
What disease in mink can lead to a monoclonal gammopathy?
viral Aleutian disease
84
MRD was detected 2 weeks or more before relapse in what % of dogs? (using PCR to measure MRD in PBMCs)
14/15 (93%)
| Sato 2011
85
What was the most sensitive test for detecting MRD, flow or PARR? (Aresu 2014)
PARR was more sensitive but the combo of flow and PARR was even more sensitive than either alone.
86
What was MST for feline high grade GI LSA treated with surgery and CHOP? (Gouldin 2015)
417d (14 months)
87
Response rate to L-spar in cats? (LeBlanc 2007)
30%
| decreased asparagine at day 2 (not day 7)
88
Was Pgp expression predictive of outcome in feline LSA? (Brenn 2008)
No
89
What metabolic abnormalities were detected with doxycycline in canine LSA patients? (Hume, McCleary-Wheeler on paper)
ELE - Five dogs developed grade 3 and/or 4 metabolic abnormalities suggestive of hepatopathy with elevations in bilirubin, ALT, ALP, and/or AST
90
What are response rates, median remission, and survival reported for single agent DOX with B cell LSA? (Higginbotham 2013)
Response rates reported for canine lymphoma treated with single-agent doxorubicin range from 69% to 74%, and median remission and survival times ranged from 131 days to 206 days and from 169.5 days to 270 days, respectively.
91
What were the results of intermittent DOX treatment for LSA? (Higginbotham 2013)
CR: 78%
median total doxorubicin remission time (TDR): 80.5 days, median overall survival (OS) was 169.5 days (5.6 months)
They gave 3 DOX doses q 2 weeks and then additional doses only when PD noted
92
What is the most common lymphoma type to occur in the stomach of cats? (Pohlman 2009, Higginbotham on paper)
Diffuse large B cell
93
What was the only prognostic factor affecting MST and DFI for cats with discrete intermediate/high grade GI LSA? (Gouldin 2015)
```
Clinical stage
(variables that were assessed but not significant = sex, breed, haematocrit, white blood cell count, serum albumin concentration, gastrointestinal obstruction and peritonitis)
```
94
What % of dogs lived longer than 1 year with VELCAP-TSC for T cell LSA? Which dogs had shorter MST? (Goodman 2016)
>30% 1 year survival
| Shorter MST for Boxers and substage b
95
ORR for 15 week CHOP? Prognostic factors? (Curran 2015)
98%
PFS 176d, LSS 311d
Prognostic factors: substage, immunophenotype, hospitalization for adverse events, need for dose reduction, neutrophilia and anemia and diagnosis, and CR
96
How does the RR to DOX single agent differ for B cell and T cell? (Beaver 2010)
B cell - 100%
| T cell - 50%
97
ORR for epitheliotropic LSA to CCNU? (Williams 2006)
78% (17% CR, 61% PR)
| In Risbon 2006, ORR was 83%
98
Is there a significant difference in DOX/placebo vs. DOX/CTX for LSA? (Lori 2010)
No
99
ORR to CCNU/pred as first line tx for LSA? Positive prognostic indicators? (Sauerbrey 2007)
53%
DLT was neutropenia, median response only 39d
Positive - higher dose, female sex (only 17 dogs in study)
100
ORR to Tanovea for relapse? (Saba 2017)
ORR 74%
| CR 45%
101
DTIC as single agent for LSA, what was ORR? (Griessmayr 2009)
35%
102
When was minimal residual disease detected before relapse? What technique was used? (Sato 2011)
MRD 2 weeks or more for 14/15 dogs
| Used PCR - amplified rearranged Ig heavy chain
103
How does presence of FoxP3+ cells in lymphoma LN compare to reactive? (Muir 2017)
Significantly fewer FoxP3 in LN effaced by LSA, but no relation to proliferation (Ki67 expression)
104
Does lymphocyte/monocyte ratio affect LSA survival? (Marconato 2015)
Yes, lymph/mono ratio <1.2 had significantly shorter TTP and LSS
105
In dogs with primary colorectal LSA, how did hematochezia correlate with survival? (Desmas 2017)
longer PFS for dogs presenting with hematochezia
106
Which IHC marker identifies lymphangiosarcoma?
PROX-1
107
Which serum biomarker is useful to predict recurrence of lymphoma in dogs that have achieved remission on chemotherapy?
a. C-reactive protein
b. TNF-α
c. LDH
d. Serum amyloid A
c. LDH
108
Which of the following factors is NOT a negative prognostic indicator in canine lymphoma?
a. Anemia
b. Hypocobalaminemia
c. p53 mutation
d. High lymphocyte:monocyte ratio
d. High lymph:monocyte ratio
LOW ratio is negative prognosticator
(Marconato 2015)
109
Which is TRUE regarding canine T-zone lymphoma?
a. German Shepherds are overrepresented.
b. Detection of lymphocytosis is rare.
c. 10% of dogs develop a second malignancy.
d. CD45 expression is a diagnostic feature.
C. 10% of dogs develop a second malignancy
