Myeloma Related Disorders

Question 1

Breed of dog overrepresented in one study of multiple myeloma

Answer 1

GSDs

Question 2

Has multiple myeloma been associated with coronavirus, FeLV, or FIV in cats

Answer 2

NO

Question 3

Over expression of what cell cycle control component may contribute to development of multiple myeloma

Answer 3

Cyclin D1

Question 4

What disease in mink results in monoclonal gammopathy

Answer 4

Viral Aleutian disease

Question 5

Grading system based on percentage of plasmablasts within neoplastic cells

Answer 5

Well differentiated = <15% plasmablasts
Intermediate-grade = 15-49% plasmablasts
Poorly differentiated = >50% plasmablasts

Question 6

What is the M component?

Answer 6

The overproduced immunoglobulin - can be single type of or component of Ig

Question 7

In dogs and cats the M component is usually __. Describe difference in makeup in dogs and cats

Answer 7

IgA or IgG for both
Dogs: IgA now thought more than IgG
Cats: IgG&raquo_space; IgA (5:1 in some reports, 1:1 in others)

Question 8

What percent of dogs in a recent study had IgA M component

Answer 8

78%

Question 9

What Ig is the M component in Waldenstrom macroglobulinemia

Answer 9

IgM

Question 10

Light chain M component has what protein

Answer 10

Bence Jones - this is rare but has been reported in dogs and cats

Question 11

What percent of dogs have radiographic evidence of bone lysis or diffuse osteoporosis in multiple myeloma

Answer 11

25-67% (1/4 - 2/3)

Question 12

Are skeletal lesions common with Waldenstrom?

Answer 12

NO - usually the malignant cells infiltrate spleen, liver, lymphoid tissue

Question 13

Way since which M components interfere with coagulation

Answer 13

Inhibiting platelet aggregation and the release of platelet factor-3

Causing adsorption of minor clotting proteins

Generating abnormal fibrin polymerization

Producing a functional decrease in calcium

Question 14

What percent of dogs have clinical evidence of hemorrhage with multiple myeloma

Answer 14

10-30% (25% of cats)

Question 15

What proportion of dogs have abnormal PT/PTT with multiple myeloma

Answer 15

Nearly half

Question 16

Hyperviscosity syndrome is more common with __. Why?

Answer 16

IgM macroglobulinemia (Waldenstrom)

Because IgM has a high molecular weight

Question 17

IgA leads to hyperviscosity syndrome why?

Answer 17

Polymerization - IgA usually is a dimer in dogs

Question 18

Hyperviscosity syndrome happens in what percent of multiple myeloma patients

Answer 18

20-40%

Question 19

What percent of retinal hemorrhage was due to multiple myeloma in a retrospective?

Answer 19

5%

Question 20

Percent of dogs and cats with renal disease secondary to multiple myeloma

Answer 20

Dogs: 25-50%
Cats: 30-40%

Question 21

Mechanisms of azotemia with multiple myeloma

Answer 21

Bence jones proteinuria
Tumor infiltration into renal tissue
Hypercalcemia
Amyloidosis
Diminished perfusion secondary to hyperviscosity syndrome
Dehydration
Ascending UTI

Question 22

What is characteristic of pure light chain (Bence jones) multiple myeloma

Answer 22

Light chains in urine without concomitant monoclonal spike in serum

Question 23

What percent of dogs and cats have Bence jones proteinuria

Answer 23

Dogs: 25-40%
Cats: 40%

Question 24

Percent hypercalcemia in dogs and cats with multiple myeloma

Answer 24

Dogs: 15-50%
Cats: 10-25%

Question 25

What is thought to regulate hyperCa in dogs with multiple myeloma

Answer 25

Osteoclast-activating factor production from neoplastic cells PTHrP has been documented in 2 dogs w/hyperCa Other factors implicated in people: increased cytokines, TNF-alpha, IL-1, IL-6

Question 26

What percent of dogs with multiple myeloma are anemic? Thrombocytopenic? Leukopenic?

Answer 26

Anemia: 50-67% (1/2 to 2/3) Thrombocytopenia: 30% Leukopenia: 80%

Question 27

What percent of cats are anemic with multiple myeloma? Thrombocytopenic? Neutropenic?

Answer 27

Anemia: 67% (2/3) Thrombocytopenia: 50% (1/2) Neutropenia: 33% (1/3)

Question 28

Med duration of clinical signs in dogs with MM before diagnosis?

Answer 28

1 month (can be present up to a year prior to diagnosis)

Question 29

MGUS

Answer 29

Monoclonal gammopathy of unknown significance NOT associated with osteolyisis, bone marrow infiltration, or Bence Jones proteinuria

Question 30

Criteria for multiple myeloma diagnosis in dogs

Answer 30

Bone marrow plasmacytosis Presence of osteolytic bone lesions M component in serum or urine

Question 31

Can a diagnosis of MM be made without osteolytic bone lesions

Answer 31

YES - if marrow plasmacytosis is associated with progressive increase in M component or if plasma cell clonality (PARR) is documented

Question 32

Is bone marrow infiltration as common in cats as in dogs and how does this affect diagnosis

Answer 32

NO - degree of infiltration in cats may not be as marked as dogs If <20% marrow plasmacytosis with atypical plasma cell morphology and visceral organ infiltration - still consistent with MM

Question 33

Can urine dip detect Bence jones proteins

Answer 33

NO

Question 34

Percent plasma cells in normal dog bone marrow

Answer 34

<5%

Question 35

Current recommendations require ___ plasmacytosis to be present in dogs, but a __ cutoff in cats has now been proposed.

Answer 35

Dogs: >20% marrow plasmacytosis Cats: >10% - even if they aren’t above this you could still have myeloma if there is cellular atypia and visceral organ involvement

Question 36

T/F: PARR can be used to determine clonality of the Ig heavy chain variable region gene in multiple myeloma and plasmacytoma

Answer 36

YES

Question 37

What percent of organs in cats with MM that had US abnormalities were confirmed to have plasma cell infiltration

Answer 37

85%

Question 38

How long before clinical signs improve with chemo with MM? Lab changes? Bone lesions?

Answer 38

Clinical signs improve within 3-4 weeks (cats 2-4 weeks) Lab changes take 3-6 weeks (Cats 8 weeks) Bone lesions may take months

Question 39

Good response to treatment is defined as

Answer 39

Reduction in the M component of at least 50% of pretreatment values

Question 40

You may see Bence Jones proteinuria respond faster than serum immunoglobulin levels. Why?

Answer 40

Bence Jones proteins have half life of 8-12h (vs. 15-20d for Ig)

Question 41

60 dogs with MM treated with melphalan - CR, PR, non-response percents?

Answer 41

CR = 43% PR = 49% No response = 8%

Question 42

MST for MM in dogs

Answer 42

540d

Question 43

Dogs - Pulse dose vs daily - objective RR, response for each protocol, med PFS, MST

Answer 43

Objective RR 86% - 96% pulse dose, 79% daily Med PFS 601d MST 930d 1y survival = 81% 2y = 55% 3y = 30%

Question 44

What percent of cats with MM respond to chemo

Answer 44

50-83%

Question 45

MST for cats with MM older paper vs. newer studyies

Answer 45

Old: 4m New: 8-13m

Question 46

Aggressive vs. less aggressive criteria for feline MM

Answer 46

Aggressive = Hypercalcemia, presence of bony lesions with pathologic fracture, low PCV, presence of light-chain Bence Jones protein in urine, azotemia, hypercreatinemia, persistence of high serum protein level after 8 weeks of treatment, little or no clinical improvement Less aggressive = Normal serum calcium, normal creatinine, blood urea nitrogen, PCV levels; presence of bony lesions without pathologic fractures, absence of light-chain Bence Jones protein, normalization of serum protein level after 8 weeks of treatment

Question 47

MST for aggressive vs. less aggressive in one study (9 cats)

Answer 47

Aggressive = 5d Non-aggressive = 387d

Question 48

Response rate for IgM macroglobulinemia to chlorambucil? MST

Answer 48

77%, MST 11m