Multiple Myeloma Flashcards
What is multiple Myeloma?
Neoplastic disease characterized by plasma cell accumulation in the bone marrow, the presence of monoclonal protein in the serum and /or urine.
What is the age range of patients presenting with MM?
98% of cases present over the age of 40
What is the incidence of MM among public?
Is the most common primary malignancy of bone.
What serum finding (IL) is common among MM patients?
Increased IL-6 as well as IgG>IgA>IgM
An increased serum monoclonal IgM production would indicate?
Waldenstrom Macroglobulinemia.
What is a primary physical finding in patients with MM?
Punch out lesions of bone
How are the punch out lesions generated?
The neoplastic plasma cells produce osteoclast activating factor which activates the RANK receptor on Osteoclasts leading to bone destruction.
What do the “punch out lesions” lead to?
Hypercalcemia and increased risk of fracture.
What would plasma cells of MM cause on serum protein electrophoresis?
An “M spike” most commonly due to monoclonal IgG IgA
What pre-existing condition usually leads to MM?
MGUS
What are the tissues most likely damaged in MM?
CRAB
- Hypercalcemia
- Renal impairment
- Anemia
- Bone disease (Back pain)
What are other concurrent findings?
- Amyloid
- Hyperviscosity
- Recurrent infections (lack of Ig diversity)
What are the characteristic immunophenotypes of the plasma cells in MM?
- CD38
2. CD138
How do you obtain a difinitive diagnosis for MM?
- M-Protein in serum or urine
- Marrow clonal plasma cells or plasmacytoma
- Related organ or tissue impairment
Using the ISS system how is MM staged?
Based on B2 microglobulin and albumin levels.
- Stage 1 B2M <3.5g/dl
- Stage 3 B2M ≥5.5
What are the poor prognostic indicators in MM?
- Del 17p
- t(4;14)
- t(14;16)
- cytogenic deletion 13
- cytogenic hypoploidy
- PCL1≥3%
- A HIGH B2M
What are the good prognostic indicators?
- Hyperdiploid
- t(11:14)
- t(6:14)
What are the revolutionary drugs currently for MM?
- IMiDs
2. Proteosome Inhibitor
How do Immunomodulatory drugs work?
1.Activates NK and T_Cell destruction of myeloma cells.
What is the proteosome inhibitor used in MM?
Bortezomib-inhibits the the cellular proteosome and NF-KB activation, resulting in destruction of MM cells.
What is the cut off eligibility age for MM transplants?
Under 70.
What is the treatment for High risk transplant ineligible patients?
MP + Bortezomib
What is the treatment for LOW risk transplant ineligible patients?
MP + IMiD
What is Waldenstrom’s Macroglobulinemia?
Low grade lymphoma which produces excess monoclonal IgM paraprotein.
What are symptoms of Waldenstrom’s Macroglobulinemia?
- Hyperviscosity- blurred vision, mental status change, ataxia
- Fatigue
- Weight Loss
- Lymphadenopathy and hepatosplenomegaly
What treatment may work in Waldenstrom’s Macroglobulinemia that won’t in MM?
Rituximab due to the disease having CD20 cells.
WHat treatment is recommended for hyperviscosity?
Plasmaphoresis
What is Amyloidosis?
A heterogeneous group of disorders characterized by extracellular deposition of protein in an abnormal fibrillar form.
Except for intracerebral amyloid plaques what are all amyloid deposits made of?
A non-fibrillary glycoprotein amylouid P which is derived from a serum precursor structurally related to C-reactive protein.
What is the classic diagnostic histological test for Amyloidosis?
Staining with Congo red and viewing under polarized light.
What is a positive Congo red test?
Red-Green bifringence.
What are the different proteins involved in the different forms of Amyloidosis?
- Systemic-Ig light chains
- Reactive systemic AA Amyloidosis-Protein A
- Familial Amyloidosis-Transthyretin
- Localized Amyloidosis-B-Amyloid protein,peptic hormones
