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Onco Board Review 2 > LSA/Leukemia > Flashcards

LSA/Leukemia Flashcards

1
Q

Dogs with trisomy of chromosome ___ have a prognostic advantage in LSA.

A

13

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2
Q

What lawn care product has been linked to LSA?

A

phenoxyacetic acid herbicides (particularly 2, 4-dichlorphenoxyactic acid; 2, 4-D)

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3
Q

What % of cats undergoing renal transplant developed cancer? What % was lymphoma?

A

24%; 36% of those were LSA

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4
Q

What % of dogs with LSA have hypercalcemia?

A

10-40%

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5
Q

The mediastinal form of LSA occurs in ___%.

A

5%

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6
Q

In a study of 37 dogs with LSA and hyperCa, what % had mediastinal LSA?

A

43%

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7
Q

What LSA cells make up hepatosplenic LSA in humans and have been reported in dogs?

A

gamma-delta-T cells

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8
Q

What % of high grade LSA are B-cell?

A

60-80%

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9
Q

Diffuse pulmonary infiltration is seen in ___ to ___% of dogs with multicentric LSA.

A

27-34%

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10
Q

Ocular involvement of LSA:

Up to ___ % have ocular changes consistent with LSA.

A

37%

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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

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12
Q

What percent of LSA dogs have lymphocytosis?

A

20%

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13
Q

What % of LSA dogs have thrombocytopenia?

A

30-50%

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14
Q

Conventional CHOP induces remission in ___ to ___% of dogs.

A

80-95%

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15
Q

MST for conventional CHOP?

A

10-12 months per Withrow, recent Thamm presentation said 12-16 months.

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16
Q

% of dogs that will be alive 2 years after initiation of CHOP?

A

20-25%

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17
Q

CR for single agent DOX with pred? MST?

A

50-75%; MST 6-8 months

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18
Q

What are three potential biomarkers of MRD?

A

serum lactate dehydrogenase, thymidine kinase 1, serum C-reactive protein

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19
Q

What % of dogs will have successful reinduction with CHOP if they relapsed after completing a CHOP-based protocol?

A

nearly 80-90%

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20
Q

What biomarkers have been associated with worse prognosis in canine LSA? (4)

A

lactate dehydrogenase, thymidine kinase, hypocobalaminemia, glutathione-S-transferase

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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)

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22
Q

In one report of 22 dogs with CLL, 68% had monoclonal gammopathies. What type of immunoglobulins?

A

Mostly IgM or IgA.

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23
Q

What PE feature is common with ALL and may be seen in CLL?

A

splenomegaly

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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)

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25
Q

What is most common form of peripheral T-cell LSA?

A

CD4+

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26
Q

What markers are characteristic of T-zone LSA?

A

CD45-, CD25+, MHCII high

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27
Q

What % of dogs with T-zone LSA have demodicosis?

A

10%

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28
Q

What is the normal distribution of T-cells, B-cells, and NK cells/double-negative T-cells in circulation?

A

80% T-cells (CD4+ outnumber CD8+)
15% B-cells
5% NK/double-negative

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29
Q

Which envelop protein is thought to be one of the mediators of immunosuppression in FeLV cats?

A

P15E

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30
Q

Per Withrow, what percentage of cats with non lymphoid hematopoietic neoplasia (myeloproliferative dz) test positive for FeLV?

A

70-90%

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31
Q

What % of cats with spinal, mediastinal, ocular, and renal LSA test positive for FeLV?

A

70%

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32
Q

The relative risk of developing LSA is ___ times higher in FeLV positive cats.

A

62

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33
Q

How does FeSV form?

A

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.

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34
Q

Cats with FeSV always test positive on what viral antigen test?

A

FeLV

tests p27

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35
Q

__% of fibrosarcomas in cats are viral induced.

A

2%

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36
Q

Metastasis to lungs or other organs occurs in approximately ___% of virally induced fibrosarcomas in cats.

A

30%

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37
Q

What is a missense mutation? Which missense mutations have been identified in canine acute myelogenous leukemia?

A

Missense mutation = nucleotide change that results in a different amino acid.
FLT3, c-KIT, RAS

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38
Q

Which gene mutation was reported in a dog with polycythemia vera that is similar to the human mutation in the same disease?

A

JAK2

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39
Q

What are the analogous chromosomes in dogs to the Philadelphia chromosome in people?

A

Philadelphia = BCR-ABL translocation btw chromosomes 9 and 22
Analogous in dogs = chromosomes 9 and 26 (Raleigh chromosome)
Associated with CML

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40
Q

What is seen in the peripheral blood in cats with FeLV myelodysplasia?

A

macrocytic erythrocytes; metarubricytosis

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41
Q

What is used to treat polycythemia vera?

A

hydroxyurea (inhibits DNA synthesis)

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42
Q

What disease in mink can lead to a monoclonal gammopathy?

A

Aleutian disease – persistent infection of autonomous parvovirus

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43
Q

What is RR of feline intermediate/large cell GI LSA to CCNU? PFS? MST? (Rau 2017)

A

50% RR
PFS 132d
MST 108d

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44
Q

What factors significantly affected PFS in cats with intermediate/large cell GI LSA treated with CCNU? (Rau 2017)

A

Hx of hyporexia
Anemia
Dose of CCNU

45
Q

Did dose intensification improve outcome for canine LSA?(Sorenmo 2010)

A

No, did not improve outcome. (note majority of dogs were stage 5b)

46
Q

What was the incidence of toxicity with dose-intensified CHOP? Did toxicity affect outcome? (Sorenmo 2010)

A

53.9% toxicity (45% needed dose adjustment/delays)

Yes, dogs with delays had longer TTP and MST.

47
Q

How did BCS affect LSA survival? (Romano 2016)

A

Obesity did not affect survival, however being underweight (BCS <4/9) at time of dx was associated with shorter survival.

48
Q

What is the RR of cats with LSA to DOX after failing COP?

A

22%

49
Q

What is the RR of cats to L-spar?

A

30%

50
Q

What is the MST with COP or CHOP for GI LGL in cats?

A

2 months (57d Krick 2008)

51
Q

T/F: Transmural infiltration is common in feline low grade T cell GI LSA.

A

False

52
Q

What % of cats with renal LSA develop CNS extension?

A

40-50%

53
Q

T/F: Epitheliotropism is common in feline nasal LSA.

A

True

54
Q

Which cells are characteristic of Hodkin’s-like LSA in cats?

A

Reed-Sternberg cells (bizarre, multinucleated)

Hodgkin’s like is usually T cell rich, B cell LSA; FeLV negative

55
Q

Which cat breed develops mediastinal LSA at a young age without being FeLV positive?

A

Siamese

56
Q

What % of cats receiving renal transplants develop LSA?

A

10%

57
Q

What is the relative risk of LSA in a cat with ETS exposure?

A
  1. 4

3. 5 with 5 or more years of exposure

58
Q

T/F: Feline small cell LSA is typically B cell.

A

False

59
Q

Which form of canine CLL has the poorest prognosis?

A

Atypical (combo of phenotypes)

T cell: 930d, B cell 480d, Atypical 22d

60
Q

What % of dogs with CLL will respond to tx with normalization of their lymph count?

A

70%

61
Q

T/F: B cells are the most common circulating lymphs in normal dogs.

A

False

62
Q

How does ocular involvement affect px in dogs with LSA?

A

Lifespan only 60-70% as long

as compared to dogs without ocular involvement when treated with COP or DOX

63
Q

What is the most common form of CLL in dogs?

A

CD8+ T-cell

64
Q

What is the RR to CCNU in dogs with epitheliotropic cutaneous LSA? DFI?

A

80%

DFI 3 months

65
Q

What is the average latency period before sarcoma development following trauma to the feline orbit? What are two negative px factors?

A

5 years

extension beyond sclera, extension into optic nerve

66
Q

What doesn’t rituximab work in dogs?

A

lack of external antigen recognition of a similar antigen on canine LSA cells

67
Q

How does rituximab work?

A

chimeric murine/human mAb directed against CD20 (found on normal pre-B and mature B lymphocytes)

68
Q

What is the RR for MOPP in rescue setting for dogs?

A

65%

31% CR

69
Q

What is the RR to CCNU/Lspar/pred in rescue setting for dogs?

A

77-87%

52-65% CR

70
Q

What is the RR to CCNU in rescue setting for dogs?

A

27%

7% CR

71
Q

What is the RR to DMAC in the rescue setting for dogs?

A

72%

44% CR

72
Q

What finding on CXR is negative px factor for canine LSA?

A

cranial mediastinal lymphadenopathy

73
Q

What % of dogs with LSA have monoclonal gammopathy?

A

6%

74
Q

What phenotype is hepatosplenic LSA?

A

gamma delta T-cell

γδT-cells

75
Q

What is the disease distribution of hepatosplenic LSA? (what organs are involved)

A

spleen, liver, BM

76
Q

Which layer of the skin does non-epitheliotropic LSA affect?

A

middle and deep portions of the dermis/subcutis

77
Q

Which chromosomal aberrations were most common in a group of 25 dogs with LSA?

A

gain of chromosomes 13 and 31

loss of chromosome 14

78
Q

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
A
  1. blasts >30% of all nucleated cells in BM

This is false, blasts are <30% per Withrow.

79
Q

What gene mutation was reported in a dog with polycythemia vera that is similar to the human mutation?

A

JAK2

80
Q

Which cell type stains for peroxidase, Sudan Black B, and chloreacetate esterase?

A

neutrophils

81
Q

Which cells are positive for CD41?

A

megakaryocytic

also CD9, CD61 - VCO 2012

82
Q

What dx test can distinguish true leukemia from a leukemoid reaction?

A

liver/spleen biopsy

83
Q

What disease in mink can lead to a monoclonal gammopathy?

A

viral Aleutian disease

84
Q

MRD was detected 2 weeks or more before relapse in what % of dogs? (using PCR to measure MRD in PBMCs)

A

14/15 (93%)

Sato 2011

85
Q

What was the most sensitive test for detecting MRD, flow or PARR? (Aresu 2014)

A

PARR was more sensitive but the combo of flow and PARR was even more sensitive than either alone.

86
Q

What was MST for feline high grade GI LSA treated with surgery and CHOP? (Gouldin 2015)

A

417d (14 months)

87
Q

Response rate to L-spar in cats? (LeBlanc 2007)

A

30%

decreased asparagine at day 2 (not day 7)

88
Q

Was Pgp expression predictive of outcome in feline LSA? (Brenn 2008)

A

No

89
Q

What metabolic abnormalities were detected with doxycycline in canine LSA patients? (Hume, McCleary-Wheeler on paper)

A

ELE - Five dogs developed grade 3 and/or 4 metabolic abnormalities suggestive of hepatopathy with elevations in bilirubin, ALT, ALP, and/or AST

90
Q

What are response rates, median remission, and survival reported for single agent DOX with B cell LSA? (Higginbotham 2013)

A

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
Q

What were the results of intermittent DOX treatment for LSA? (Higginbotham 2013)

A

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
Q

What is the most common lymphoma type to occur in the stomach of cats? (Pohlman 2009, Higginbotham on paper)

A

Diffuse large B cell

93
Q

What was the only prognostic factor affecting MST and DFI for cats with discrete intermediate/high grade GI LSA? (Gouldin 2015)

A 
Clinical stage
(variables that were assessed but not significant = sex, breed, haematocrit, white blood cell count, serum albumin concentration, gastrointestinal obstruction and peritonitis)
94
Q

What % of dogs lived longer than 1 year with VELCAP-TSC for T cell LSA? Which dogs had shorter MST? (Goodman 2016)

A

> 30% 1 year survival

Shorter MST for Boxers and substage b

95
Q

ORR for 15 week CHOP? Prognostic factors? (Curran 2015)

A

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
Q

How does the RR to DOX single agent differ for B cell and T cell? (Beaver 2010)

A

B cell - 100%

T cell - 50%

97
Q

ORR for epitheliotropic LSA to CCNU? (Williams 2006)

A

78% (17% CR, 61% PR)

In Risbon 2006, ORR was 83%

98
Q

Is there a significant difference in DOX/placebo vs. DOX/CTX for LSA? (Lori 2010)

A

No

99
Q

ORR to CCNU/pred as first line tx for LSA? Positive prognostic indicators? (Sauerbrey 2007)

A

53%
DLT was neutropenia, median response only 39d
Positive - higher dose, female sex (only 17 dogs in study)

100
Q

ORR to Tanovea for relapse? (Saba 2017)

A

ORR 74%

CR 45%

101
Q

DTIC as single agent for LSA, what was ORR? (Griessmayr 2009)

A

35%

102
Q

When was minimal residual disease detected before relapse? What technique was used? (Sato 2011)

A

MRD 2 weeks or more for 14/15 dogs

Used PCR - amplified rearranged Ig heavy chain

103
Q

How does presence of FoxP3+ cells in lymphoma LN compare to reactive? (Muir 2017)

A

Significantly fewer FoxP3 in LN effaced by LSA, but no relation to proliferation (Ki67 expression)

104
Q

Does lymphocyte/monocyte ratio affect LSA survival? (Marconato 2015)

A

Yes, lymph/mono ratio <1.2 had significantly shorter TTP and LSS

105
Q

In dogs with primary colorectal LSA, how did hematochezia correlate with survival? (Desmas 2017)

A

longer PFS for dogs presenting with hematochezia

106
Q

Which IHC marker identifies lymphangiosarcoma?

A

PROX-1

107
Q

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

A

c. LDH

108
Q

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

A

d. High lymph:monocyte ratio
LOW ratio is negative prognosticator
(Marconato 2015)

109
Q

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.

A

C. 10% of dogs develop a second malignancy

Onco Board Review 2 (20 decks)

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