Flashcards in Chapter 18: Multiple Myeloma Deck (37):
What is paraproteinemia?
The presence of a monoclonal immunoglobulin band in the serum.
What is Multiple myeloma?
Multiple myeloma is a neoplastic proliferation of plasma cells usually in the bone marrow.
What is the epidemiology of multiple myeloma?
98% of cases occur over the age of 40 with a peak incidence in the seventh decade (60's). More common among afro-caribbeans.
What are the characteristics of the myeloma cell?
Myeloma cells are post-germinal center plasma cells that have undergone class switching and somatic hypermutation. The immunophenotype is
(1) CD38 high
(2) CD138 high
(3) CD 45 low.
What is the cause of multiple myeloma?
The genetic changes involved in multiple myeloma are complex, but they usually involve
(1) increased or dysregulated expression of cyclin D
(3) translocation of the IgH locus.
(4) 13q deletion.
What growth factor is important for myeloma cells?
How is multiple myeloma diagnosed?
(1) monoclonal protein in serum or urine.
(2) increased plasma cell in the bone marrow
(3) Related organ or tissue impairment
What sorts of organ impairment occur in multiple myeloma?
(1) bone disease/hypercalcemia
(2) renal impairment
(4) hyperviscosity (2%)
(5) amyloidosis (5%)
What is smouldering or asymptomatic myeloma?
Myeloma that is characterized greater than 10% plasma cell count in the bone marrow without organ impairment.
What causes the bone pain and hypercalcemia associated with multiple myeloma?
In multiple myeloma over expression of RANKL by the bone marrow stroma leads to activation of oseoclasts that breakdown bone leading to hypercalcemia and pathologic fractures.
What are the four major signs and symptoms of multiple myeloma?
(1) Calcium increased
(2) renal failure
(4) bone lesions.
Why do patients with multiple myeloma experience recurrent infections?
Because multiple myeloma leads to deficient antibody production and neutropenia.
What leads to the renal failure associated with multiple myeloma?
Deposition of light chains and calcium in the kidneys.
Why do multiple myeloma patients experience increased bleeding?
Because myeloma proteins interfere with platelet function and coagulation factors.
How often does amyloidosis occur secondary to multiple myeloma?
Amyloidosis occurs in about 5% of multiple myeloma patients.
How is the presence of paraprotein in the serum assayed?
By immunoglobulin electrophoresis. (usually IgG or IgA)
What is unusual about the blood cells in patients with multiple myeloma?
Rouleaux formation (with normocytic/normochromic anemia)
What abnormal laboratory values are associated with multiple myeloma?
(1) High ESR
(2) High CRP
(3) elevated serum calcium
(4) Elevated creatinine (20%)
(5) Serum Beta-2-microglobulin increased (associated with a poor prognosis)
Is multiple myeloma curable?
Usually not! only younger patients who can undergo a successful allogenic stem cell transplant have a hope for a cure.
How is intensive therapy used to treat multiple myeloma?
Intensive therapy is reserved for patients under the age of 65. it involves chemotherapy and autologous stem cell transplant.
How is non-intensive therapy used to treat multiple myeloma?
In older patients melphalan is used in conjunction with prednisolone. Thalidomide or cyclophosphamide may also be used.
What is the effect of bortezomib on multiple myeloma?
Bortezomib is a proteosome inhibitor that stops NFkB activation
How is radiotherapy used to treat multiple myeloma?
Radiotherapy is useful for treating the symptoms of multiple myeloma including bone pain
What supportive care is given to patients with multiple myeloma to manage renal failure, bone disease, paraplegia, anemia, bleeding, and infections?
(1) rehydration and dialysis for renal failure
(2) Bisphosphonates for bone disease and hypercalcemia
(3) radiation for compression paraplegia
(4) transfusion/EPO for anemia
(5) Plasmapharesis helps with bleeding
(6) Prophylaxis with antimicrobials and Ig infusions.
What is the prognosis for multiple myeloma?
High albumin and low beta-2 microglobulin are associated with a better prognosis. High beta-2 microglobulin and low albumin are associated with a poor prognosis. median survival is 3-4 years with non-intensive therapy
What are solitary plasmacytomas?
isolated plasma cell tumors usually of bone, respiratory tract, or GI tract. Lesions disappear after radiotherapy.
What is plasma cell leukemia?
20% or more plasma cells in the blood can be primary or secondary to multiple myeloma. The prognosis is poor
What is heavy chain disease?
A disorder in which cells secrete and incomplete heavy chain. Most common in mediterranean areas and starts with a malabsorbtion syndrome
What is Waldenstrom's macroglobulinemia (WM)?
A rare condition characterized by lymphoplasmacytoid lymphomas that secrete monoclonal IgM. Occurs most commonly in men over 50.
How does WM usually present?
(2) weight loss
(3) Neurological symptoms
(5) heart failure
What secondary complications can result from WM?
(1) hyperviscosity (due to IgM)
(2) Visual problems (engorged retina)
(3) Anemia (from increased plasma volume)
(4) Bleeding (due to inhibition of platelets)
How is WM diagnosed?
(1) monoclonal IgM
(2) Lymph node in filtration by lymphoplasmacytoid cells.
(3) peripheral blood lymphocytosis.
What specific treatments are used for WM?
Chlorambucil or cyclophosphamide are the mainstays of therapy. Rituximab may also be used. SCT may be considered in severe cases.
What supportive therapies are used for WM?
(1) plasmapheresis for hyperviscosity
(2) EPO for anemia.
What is monoclonal gammopathy of undetermined significance (MGUS)?
MGUS is characterized by transient or persistent paraproteins in the serum without evidence of myeloma or other underlying disease.
Why does systemic amyloidosis sometimes develop secondary to myeloma?
Because the deposition of Ig light chains can cause amyloidosis.