Bachata Rosa Flashcards
Mutation and overexpression of what gene is present in both human and canine LSA?
What other TSG was also recently evaluated and found to be abnormal in both human and canine B-LSA?
p53 - lower remission rate and ST
Mutated in 16% and overexpressed in 22% of dogs with high-grade LSA
Hypermethylation of DAPK CpG islands - 45% of B-cell LSA; negative PI for survival in both humans and dogs
DAPK involved in IFN-y mediated apoptosis
What is the most common immunophenotype and cytomorphologic sub-classification of LSA in Boxers?
85% T-cell lymphoma
TCR ab+, CD4+
Lymphoblastic high-grade
What is the MST of Boxers and Boxer mix breeds when treated with the LOPP chemotherapy protocol? Prognostic indicators found?
MST - 3m (99d)
Boxers 6x more likely to develop PD
Boxer breed = negative PI for PFI
What is Ritcher’s syndrome and the MST* in dogs?
CLL -> lymphoma
Characterized by the presence of pleomorphic immunoblasts
Poor tx response and prognosis
MST 41d
What are the identified prognostic factors in dogs with CD21+ LSA (2)?
Large cell size = shorter remission duration and ST (HR: 2.77x more likely to die and 1.75x more likely to develop PD); also more likely to have lymphadenopathy and thrombocytopenia
MST: large cell 5m vs medium 9m vs small NR
Low MHC class II = shorter remission duration and ST (HR: 2.87x more likely to die and 3.49x more likely to develop PD)
MST: low 4m vs high 10.5m
What is the PFS* and MST in dogs with LSA treated with CCNU as a first line therapy? ORR? CR and PR?
PFS: 40d
MST 3.5m (111d)
ORR 52%, CR 35%, PR 17%
What is the PFS, and MST of dogs with LSA when treated with doxo/pred vs doxo/pred/CTX?
Main findings on this study?
Addition of CTX did NOT result in statistical improvement of ORR, PFS, or MST. Study was underpowered, however.
Doxo/pred/placebo - PFS 5 to 6m, MST 6 to 10m
Doxo/pred/CTX - PFS 8m, MST 14m
CR, PFI, MST with single agent doxo/pred in dogs with LSA of unknown phenotype?
ORR, CR, PFI, MST for B-cell?
ORR and CR* for T-cell?
Unknown: CR 78% PFS 4-6m, MST 5-10m
B-cell: ORR 100%, CR 70 to 86%, PFS 5-6m, MST 6-10m
Only chemo completion prognostic for PFS and ST; no diff when compared to historic controls that included T cell
T-cell: ORR 50%, CR 17%
CR to CHOP for T-cell vs B-cell canine multicentric LSA?
T-cell 88% (ORR 95%, PFI 5m, MST 8m)* largest study with specifically multicentric T-cell (no GI); 15% alive at 1 yr and 5% at 2 yr
B-cell 85 or >%
MOPP for T-cell: ORR 98%, CR 78%, PFI 6.3m, MST 9m)
25% alive at 2.5yrs
Main findings of RNA-loaded CD40-activated B-cells in dogs with spontaneous lymphoma?
Used CD40L transfected K562 cells to generate functional CD40-B cells from the peripheral blood of humans and dogs
It was administered to dogs in remission after induction of chemotherapy
Goal: Induce functional tumor-specific T cells in cancer patients
- CD40 activated B cells are highly efficient antigen-presenting cells capable of priming naive T cells, boosting memory T-cell responses and breaking tolerance to tumor antigens
- The use of tumor RNA as the antigenic payload allows for gene transfer without viruses or vectors and permits MHC-independent, multiple-antigen targeting
RESULTED IN:
-Higher % of dogs achieving a durable 2nd remission and improved lymphoma specific ST in relapsed dogs after rescue therapy
-Induced functional, antigen-specific T cells from healthy dogs and dogs with lymphoma
DID NOT affect: initial response, TTP, or ST compared to dogs tx with chemo alone
What is the ORR, CR, and PFI in dogs with NAIVE lymphoma when treated with alternating rabacfosadine/doxorubicin?
How does immunophenotype affect ORR?
Prognostic indicators (2)?
ORR 84% (CR 68%, PR 16%)
PFI 6.5m, if CR 7.2m
Immunophenotype predicted ORR:
95% - B cell
25% - T-cell
Substage and phenotype were associated with PFI; longer for B-cell
What is the ORR, CR, and PFI in dogs with B-cell LSA when treated with rabacfosadine in the RESCUE setting?
How does the PFI change for dogs with a CR or any response?
ORR: 74% (CR 45%, PR 29%)
PFI: 3.5m, 7m if CR, 6m with any response
No difference between doses used
What % of dogs with lymphoma vs myeloma develop dermatologic AE when treated with Tanovea?
Lymphoma: 25-37%
Myeloma: 50%
What is the most common phenotype, overall PFS and MST in dogs with colorectal lymphoma?
Does local therapy improve outcome?
B-cell, high-grade
PFS 3.6yrs
MST: 4-5yrs
Addition of local therapy to chemotherapy DOES NOT improve outcome
ORR, CR, PR to chemotherapy in dogs with colorectal LSA?
100% ORR
95% CR
5% PR
Prognostic factors in dogs with colorectal LSA (2)?
Younger dogs (<7yrs) = longer PFS (NR) and dz-specific MST
Hematochezia/substage b = longer PFS (NR)
What is the most common intestinal location in cats with LGL?
Most common phenotype?
IHC used for granules?
What % is NK origin?
Jejunum
granzyme B+ for granules (seen on cytology but not H&E sections)
CD3+ CD8+, CD20-, TCR gene rearrangement - most common
CD103 (integrin) - 60%
10% are NK origin (CD57+) and negative for B and T cell markers; C
What % of cats with LGL experience clinical benefit and a response when treated with chemotherapy?
35% - clinical benefit
30% - ORR
What is the overall TTP and MST in cats with LGL when treated with chemotherapy? MST w/o chemo? What % survives >7m?
TTP 50d
MST 2m; CHOP 60d, CCNU 60-130d
MST w/o chemo 2w
7% >6m SR
CHOP/COP ORR 30%
CCNU/Elspar ORR 56%
Negative prognostic indicators in cats with LGL (4)? Positive (1)?
- Substage b
- Circulating neoplastic cells
- Lack of chemo administration
- Lack of chemo response
Positive: chemo administration
What are the negative (4) and positive (3) prognostic factors identified in cats with nasal LSA?
Negative:
- Anemia
- Cribriform plate lysis
- Total RT dose of <32Gy
- BW of <4kg
Positive:
- Achievement of a CR
- Total RT dose of >32Gy
- Apoptotic index and Ki67 >40%
What is the overall MST in dogs with intermediate to high vs low-grade nasal LSA? Most common phenotype?
B-cell
Intermediate to high - MST 12.5m
Low - MST 2.3yr
No statistical difference in MST, but chemo alone had lowest MST of 5m vs RT + chemo MST of 15m
Most common primary and metastatic* intramedullary spinal tumor in dogs? Location?
Primary - ependymoma (neuroepithelial)
Metastatic- HSA and LSA per Withrow
HSA and TCC new paper; 33% each
T3-L3
Most common secondary brain tumor in cats vs dogs?
Cats - LSA #1, pituitary #2
Dogs - HSA #1, pituitary #2, LSA #3