PLasma Cell disorders

Question 1

What is multiple myeloma characterized by?

Answer 1

neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin.

bone marrow is making cancerous blood cells which in turn is weakenng your bones

Question 2

Where do plasma cells develop from?

Answer 2

B Lymphocytes

Question 3

What do plasma cells produce?

Answer 3

antibodies

Question 4

Where are plasma cells mainly present in?

Answer 4

bone marrow and lymph npdes

Question 5

How do plasma cells divide?

Answer 5

Divide repeatedly to form a clone of many identical cells

Many clones=vast number of antibodies

Question 6

What are the signs and symptoms of multiple myeloma related to?

Answer 6

the infiltration of plasma cells into the bone or other organs or to kidney damage from excess light chains (protein subunt that forms part of the antibody).

Question 7

Is MM curable?

Answer 7

incurable progressive neoplasm. treatable. some pt can live up to 7 -10 years

Question 8

Multiple Myeloma is highly associated with what?

Mildly associated with what?

Answer 8

Anemia – 73%
●Bone pain – 58%
●Elevated creatinine – 48%

Fatigue/generalized weakness – 32%

●Hypercalcemia – 28%

●Weight loss – 24%

Question 9

What can the anemia be associated with in MM and what kind of anemia is it?

4

Answer 9

Normocytic, normochromic anemia

This anemia can be related to:
Bone marrow replacement
Kidney damage
Dilution in the case of a large M-protein
B12 deficiency in 14%

Question 10

Conventional radiographs abnormal 80% of patients who present with multiple myeloma. What kinds of bone disease can be present?
4

Answer 10

1. Osteopenia or osteoporosis 20%
2. Focal lytic (destructive) bone 57%%- punched out lesiosns in skull for example
3. Pathologic fractures 20%
4. Vertebral body compression fractures 20%

These are fractures that can happen without an trauma. There must be a malignancy somewhere.

Question 11

How will renal failure present in the 50% of patients that has MM?

Answer 11

serum creatinine is increased

Question 12

What is this renal failure due to?

4

Answer 12

1. Light chain cast nephropathy (also called myeloma kidney)
2. Hypercalcemia (binding of the monoclonal protein w/ calcium)
3. Concurrent Light chain amyloidosis (deposition of amyloid-abnormal protein produced in marrow- that deposits in tissue)
4. Drug-induced renal damage

Question 13

Symptoms and signs in less than 5% of MM pts?

8

Answer 13

paresthesias/neurologic disease
hepatomegaly
splenomegaly
lymphadenopathy 
Infections
CNS involvement
pleural effusion & pulmonary involvement
extramedullary plasmacytomas (7%) - red purple nodules or lesions

Question 14

Patients suspected of having multiple myeloma (MM) should initially undergo what??

Answer 14

complete history and physical examination!!!!!!

Question 15

The history should pay specific attention to complaints of what?
4

What about the physical exam?

Answer 15

1. bone pain,
2. constitutional (the i dont feel goods) symptoms,
3. neurological symptoms, and
4. infections.

The physical examination should include a detailed neurologic exam

Question 16

What labs would we do for MM?

8

Answer 16

1. CBC with diff, peripheral blood smear
2. CMP; kidney function and calcium
3. LDH
4. beta-2 microglobulin (protein inc. with cell turn over)
5. C-reactive protein
6. Serum protein electrophoresis (SPEP) + IF Quantification of immunoglobulins
7. Urinalysis and a 24-hour urine collection for electrophoresis (UPEP) + IF
8. Serum free monoclonal light chain (FLC)

CBC with diff and smear
beta-2 microglobulin
CMP w/ kidney function and Ca
LDH
CRP
SPEP and Ig quantifications
Urinalysis + IF
FLC

Question 17

What would you look for on the blood smear for MM?

Answer 17

Rouleaux Formation!

Cell stacked like coins (elevated serum proteins level)

Question 18

In an abnormal SPEP where will the spike be to indicate a positive test?

Answer 18

gamma globulin spike

Question 19

What is monoclonal gammopathy characterized by?

Answer 19

disorder characterized by proliferation of a single clone of lymphoid or plasma cells

Question 20

What is hyperviscoity due to in MM?

Answer 20

Excess protein. This protein is most likely IgM

Question 21

When should serum viscosity be checked in MM?

Answer 21

If the M protein (IgM) is high

Question 22

What three procedures should be done in patients with MM for evaluation?

Answer 22

1. Bone marrow aspiration and biopsy with immunophenotyping
2. conventional cytogenetics (function of cells in chromosomes)
3. fluorescence in situ hybridization (FISH)-looks for chromosome abnormalities

Question 23

What imaging should we have done with MM?

Answer 23

MRI, CT, or PET/CT

Question 24

How would we see lytic changes in the bone that would definitely point to abnormalitites and possibly MM?

Answer 24

Metastatic bone survey with plain radiographs including the humeri and femoral bones should be performed in all patients

Question 25

What is the pathologist looking for in a bone marrow biopsy in an MM pt?

Answer 25

clonal plasma cells | 10% or more of clonal plasma cells

Question 26

Best imaging test for MM dx? What kind of patients would we do this in? 3

Answer 26

PET scan looking for metabolic areas --pt with compression facture or neurological deficient, or any uncertainty about the extent of the bone disease This is an emergency

Question 27

For the diagnosis of MM what needs to be present? 3

Answer 27

1. Presence of a serum or urinary monoclonal protein 2. Presence of clonal plasma cells in the bone marrow or a plasmacytoma 3. Presence of end organ damage felt related to the plasma cell dyscrasia (malfunction)

Question 28

What are examples of end organ damage felt related to the plasma cell dyscrasia? 4 M-CRAB

Answer 28

Increased calcium concentration Lytic bone lesions Anemia Renal failure M-CRAB ``` Monoclonal protein (Lab test) Calcium Renal failure Anemia Bone marrow +/bone pain with lytic lesions ```

Question 29

Five other types of myeloma?

Answer 29

``` Monoclonal gammopthy of undetermined significance Smouldering myeloma- Intramedullary myeloma Extramedullary myeloma Myeloma cell line ```

Question 30

Monoclonal Gammopathy of Undetermined Significance (MGUS). What criteria must be met for diagnosis? What would we do with this present?

Answer 30

1. Serum monoclonal protein

Question 31

Smoldering Multiple Myeloma SMM. What criteria must be met to diagnose this? 3

Answer 31

1. Serum monoclonal protein ≥3 g/dL and/or 2. bone marrow plasma cells ≥10 percent 3. . No end organ damage related to plasma cell dyscrasia

Question 32

MM: Indications for Treatment | 5

Answer 32

1. Anemia (hemoglobin 11.5 mg/dL) 3. Renal insufficiency (serum creatinine>2 mg/dL) 4. Lytic bone lesions or severe osteopenia 5. Extramedullary plasmacytoma Maybe a FISH test looking for abnormalities in chromosome

Question 33

MM: RISK STRATIFICATION | risk identification for the pt?

Answer 33

FISH for detection of t(4;14), t(14;16), and del17p13 Conventional cytogenetics (karyotyping) for detection of del 13 or hypodiploidy The presence of any of the above markers defines high risk myeloma, which encompasses the 25% of MM patients who have a median survival of two years or less despite standard treatment

Question 34

MM: INITIAL THERAPY | 2

Answer 34

The initial therapy of patients with symptomatic myeloma varies depending on whether patients are eligible or not to pursue autologous hematopoietic cell transplantation Chemo: Survival equal or less than 3 yrs Tranplantation: 4-5 yrs (perfered but sometimes they are not a candidate for surgery)

Question 35

Key issues with stem cell transplantation? | 5

Answer 35

1. Efficacy compared with conventional chemotherapy 2. Timing: early vs delayed (have to monitor the disease to decide when) 3. Single vs tandem (hit you with one and then another) 4. Role of allogeneic and miniallogeneic transplantations - --dont use a lot of chemo proir to stem cells acquired from another person)- risk? host vs craft and relapse increase because of no chemo 5. Maintenance post-SCT common: chemo followed by autologous

Question 36

Could use Immunomodulatory drugs (IMiDs) to treat. What are they?2 Same with proteasome inhibitors. What are they?2

Answer 36

Thalidomide Lenalidomide Bortezomib Carfilzomib

Question 37

If a patient is clearly not a transplantation candidate based on age, performance score, and comorbidity what route would we take?

Answer 37

MPT, MPV, Len/dex or clinical trial* Melphalan/prednisone Chemo drug plus steroid

Question 38

If a patient is a potential transplantation | candidate for MM treatment what would we start treatment with?

Answer 38

1. Induction therapy- reduce the number of plasma cells before we transplant - -We would use a nonalkylator based induction X4 cycles 2. Then we would harvest stem cells for furture transplantation

Question 39

Induction therapy may consist of one or a combination of the following types of drugs: 3

Answer 39

chemotherapy targeted therapy corticosteroids

Question 40

What is waldenstrom macroglobulinemia?

Answer 40

is a type of non-Hodgkin lymphoma (NHL) . The cancer cells make large amounts of an abnormal protein (called a macroglobulin). Lymphoplasmacytic lymphoma in bone marrow with an IgM monoclonal gammopathy in the blood. Usually doesnt cause that many problems. Effects are due to infiltration of hematopoietic tissues

Question 41

The most common presenting features of WM include? | 4

Answer 41

weakness, fatigue, weight loss, and chronic oozing of blood from the nose or gums ``` Other symptoms: ●Asymptomatic — 25% ●Constitutional symptoms — 23% ●Bleeding — 23% ●Neurologic symptoms — 22% ●Hyperviscosity (HA, vertigo, diplopia) — 31% ●Lymphadenopathy — 25% ●Hepatomegaly — 24% ●Splenomegaly — 19% ●Funduscopic abnormalities — 34% ```

Question 42

What symptoms are due to tumor infiltration in WM? | 6

Answer 42

``` Anemia/Cytopenia Fever Night sweats Weight loss Lymphadenopathy Organomegaly ```

Question 43

What symptoms are due to monoclonal IgM? | 5

Answer 43

``` Hyperviscosity Cryoglobulinemia Cold agglutinin Neuropathy Amyloidosis ```

Question 44

WM: Lab Evaluation | 9

Answer 44

1. Complete blood count 2. Platelet function and blood coagulation 3. Bone marrow examination 4. Serum protein electrophoresis 5. Serum viscosity 6. Serum free light chain assay 7. Immununofixation 8. Serum ß2-microglobulin—for prognostic evaluation. 9. CT

Question 45

What is the criteria to diagnose WM? | 3

Answer 45

1. An IgM monoclonal gammopathy must be present in the serum. 2. 10% or greater of the bone marrow biopsy must demonstrate infiltration by small lymphocytes that exhibit plasma cell differentiation

Question 46

Treatment of asymptomatic WM pt with adequate hgb and platelets?

Answer 46

Observe, no treatment

Question 47

How would we treat Symptomatic WM?

Answer 47

rituximab (either alone or with other agents) rather than chemotherapy alone (cyclophosphamide )

Question 48

If the WM pt has a high tumor burden and meets transplant requirements what kind of transplant should they have?

Answer 48

hematopoietic cell transplantation (HCT)

Question 49

If the patient is hyperviscous how should we treat them?

Answer 49

``` therapeutic plasmapheresis (remove affected blood from the body, take out the diseased plasma and put it back in) ```