Multiple Myeloma -Krafts/Johns

Question 1

Multiple Myeloma

Things you must know:

Answer 1

• Monoclonal plasma cell proliferation
• Monoclonal gammopathy
• Decreased normal Ig’s
• Osteolytic lesions

Question 2

Lab findings

Answer 2

• M-spike: a bunch of Ig’s that come from monoclonal plasma cell
• Type of IgG
  
  • IgG in 60% of cases -most common
  • IgA in 20% of cases
  • IgD or IgE in rare cases
  • Never IgM
• Bence-Jones protein in urine -
  
  • sometimes myelomas only make light chains
• Decreased normal Ig

Question 3

Morphology?

Blood:

Bone Marrow:

Answer 3

Blood: anemia, rouleaux (RBC stacking up)

Marrow: plasma cells, amyloid (collection of light chains that plasma cells are making)

Flame cells, Russel bodies (in cytoplasm), Dutcher body (in nucleus)

Lots of russel bodies == Mott cell

Question 4

Other Plasma Cell Tumors

1. solitary plasmacytoma
2. Plasma cell leukemia
3. Waldenstrom macroglobulinemia
4. MGUS

Answer 4

• Solitary plasmacytoma–localized myeloma
• Plasma cell leukemia – presents de novo or end result of myeloma
• Waldenstrom macroglobulinemia –
  
  • Lymphoplasmacytoid lymphoma –but act and look like plasma cells
  • Cells make IgM
  • Hyperviscosity syndrome – blood sludges in eye –> retinal problems
• MGUS (Monoclonal gammopathy of undetermined significance)
  
  • Small M spke with no myeloma symptoms
  • Occasionally transforms into myeloma

Question 5

Biology of normal plasma cells:

Answer 5

Plasmablasts in lymph nodes (IgM)

—> Activated B cells in bone marrow (IgG, IgA)

—>Differentiate inot plasma cells

(small in #, well-differentiated, characteristic phenotype, die by apoptosis)

Question 6

Biology of Malignant plasma Cell:

Answer 6

Plasmablasts in lymph nodes

—>plasmablasts in BM (IgG, IgA)

—>Plasmablasts do not differentiate into plasma cells, continue to proliferate and accumulate in marrow, produce lots if Ig’s,

normal cell death does not occurs, crowds out other cells

Suppress antibody synthesis by normal plasma cells

Question 7

Clinical Features:

Answer 7

• Bone pain –associated with multiple lytic bone lesions
• Bruising or bleeding from decreased platelets
• Infections from decreased levels of normal Igs
• Hypercalcemia from bone destruction
• renal failure
• Hyperviscosity syndrome

Question 8

Classic Triad?

Answer 8

Anemia

bone pain

renal failure

Question 9

Major cause of death?

Answer 9

Infection

Renal Failure

Question 10

Criteria for Diagnosis:

Answer 10

1. BM with >20% plasma cells OR
2. Plasmacytoma plus one of:

• Monoclonal protein in serum > 3 g/dl
• Monoclonal protein in urine
• lytic lesions

3. Usual clinical features of myeloma
4. Exclude CT diseases, chronic infections, carcinoma, lymphoma, leukemia

Question 11

Therapy:

Answer 11

• Symptomatic disease (active) – treat immediately
• Tx strategy related to age and other conditions
• NOT A CURABLE DISEASE

Question 12

Classic Agents for Tx:

Answer 12

Dexamethasome - steriod

Melphalan - alkylating agent

Cyclophosphamide -alkylating agent

Question 13

Autologous peripheral blood stem cell transplant (PBSC)

Answer 13

• Hematopoietic stem cells from peripheral blood
• Growth factors given after transplant
• Problem - contamination of autologous graft by myeloma cells

Question 14

New agents?

Answer 14

Thalidomide: antiangiogenic agent

Lenalidomide: newer antiangiogenic agent

Bortezomib: proteasome inhibitor

Question 15

New Supportive Therapies

Answer 15

Biphosphonates - inhibit bone resorption, treats bone lesions and hypercalcemia

Erythropoietin - helps anemia and decreases need for transfusions

Question 16

Prognosis:

Answer 16

Conventional Chemo: 3-4 years

Intensive therapy: depends on age

Question 17

Causes of Death:

Answer 17

marrow replacement with pancytopenia (16%)

Renal failure (10%)

Acute leukemia (5%)

other chronic illnesses (23%)