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Flashcards in Myeloma Deck (27)

51 yr old male, epigastric distress, weight loss, low hemoglobin (extremely), Very high creatinine [severe anemia, acute renal failure with proteinuria, epigastric distress, weight loss] What does he have?

Multiple Myeloma


What does a bone marrow slide look like in multiple myeloma?

-Large, odd looking plasma cells, eccentric nucleus with a little clearing where golgi is --> sometimes binucleate
-Usually you need at least 30% odd cells/plasma cells to be myeloma


What things MUST you know about multiple myeloma?

-Monoclonal plasma cell proliferation
-Monoclonal gammopathy
-Decreased normal immunoglobulins
-Osteolytic lesions


What are the laboratory findings in multiple myeloma?

-M-spike on serum protein electrophoresis
-Type of IgG
---IgG in 60% of cases
---IgA in 20% of cases
---IgD or IgE in rare cases
---Never IgM (may be very rare case)
-Bence-Jones protein in urine
-Decresed normal Ig


What are Bence-Jones proteins? Where are they found?

-Light chains made with no heavy chain counterpart that clump up
-Protein in urine in multiple myeloma


What is seen in the blood of multiple myeloma patients?

Anemia, Rouleaux (red cells stacking up on each other)


What is seen in the bone marrow of multiple myeloma?

Plasma cells, amyloid (composed of light chains plasma cells make)


What do you see in bone marrow of multiple myeloma patients?

-Little fat, monomorphous (similar) cells, lots of cell proliferation
-Shows many many malignant plasma cells
-Sometimes the cells look like mature plasma cells, sometimes they look like blasts --> developmental stage is not correlated to clinical outcome for the patient
-Flame cells, Russell bodies (collections of Ig - abnormally formed immunoglobulin chains)
-Dutcher body (gray circle in nucleus) & Mott cell (large white circles of all shapes in cytoplasm)
-Rouleaux: red cells stacking on top of each other


What are four other plasma cell tumors?

1. Solitary plasmacytoma
2. Plasma cell leukemia
3. Waldenstrom Macroglobinemia
4. MGUS (monoclonal gammopathy of undetermined significance)


What is solitary plasmacytoma?

Localized myeloma - single focus of clonal plasma cells that don't go anywhere


What is Plasma cell leukemia?

Presents de novo or its an end result of myeloma


What is Waldenstrom Macroglobinemia (EXAM!!)?

-Lymphoplasmacytoid lymphoma
-Hyperviscosity syndrome - causing retina symptoms


What is MGUS?

Monoclonal gammopathy of undetermined significance
-Small M spike with no myeloma symptoms
-Occassionally transforms into myeloma
-Not malignant but you watch this one!


What will serum and urine immunoelectrophoresis show in multiple myeloma?

Monoclonal IgA kappa protein/fragment


What is the biology of normal plasma cells and how do malignant plasma cells differ?

1. Plasmablasts in lymph nodes (IgM)
2. Activated B cells in bone marrow (IgG, IgA)
3. Differentiate into plasma cells (small in number, well-differentiated, characteristic phenotype, die by apoptosis)
--Malignant plasma cells stay plasmablsats in the bone marrow (with IgG, IgA). Then they do not differentiate into plasma cells but continue to accumulate in bone marrow, produce many Ig, normal death of cells doesn't occur, crowds out other cells like rbc precursors - suppresses antibody synthesis by normal plasma cells


What are some of the clinical features seen in Multiple Myeloma?

-80% of patients present with bone pain (low back, pelvis, or ribs). Pain is associated with lytic bone lesions
-Bruising or bleeding - dec. platelets
-Infections -dec. levels of normal Ig
-Multiple lytic lesions (skull, arms, etc.)
-Pathological fractures
-Bone destruction (osteoclasts) may also cause hypercalcemia!
-Hypercalcemia from bone destruction
-50% of patients present with renal failure
-Hyperviscosity syndrome - caused by large amounts of circulating Ig causing purport, confusion, decreased vision


What is the 'Classic triad' seen in multiple myeloma?

-Anemia, bone pain, renal failure!


What is the major cause of death in MM?

Infection, renal failure


What is the average age of diagnosis for multiple myeloma?

69 years (can be as young as 40 in some cases through)


What criteria is used for diagnosis of MM?

1. Bone marrow with >20% plasma cells OR
1. Plasmacytoma plus one of the following: Monoclonal protein in serum > 3 g/dl, monoclonal protein in urine, lytic lesions
2. Usual clinical features of myeloma
3. Exclude connective tissue disease, chronic infections, carcinoma, lymphoma, leukemia


How should therapy for MM be adjusted?

-Symtomatic disease (active) should be treated immediately
-Treatment strategy related to age and coexisting conditions (heart, lung, kidneys)


What are the classic agents used to treat multiple myeloma and how do they work?

1. Dexamethasone - steroid
2. Melphalan - alkylating agent
3. Cyclophosphamide - alkylating agent


How does an autologous peripheral blood stem cell transplant (PBSC) work?

-Hematopoietic stem cells from peripheral blood
-Growth factors are given after transplantation
-Safe - 1-2% death rate from the transplantation
-Problem: contamination of the autologous graft by myeloma cells


What are three newer agents used to treat multiple myeloma?

1. Thalidomide - antiangiogenic agent: first used with advanced and refractory myeloma (2001)
2. Lenalidomide - newer antiangiogenic agent
3. Bortezomib - proteasome inhibitor


What did the study say about using lenalidomide as maintenance after Stem-Cell transplantation for MM?

-Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma
-Four years after randomization, overall survival was similar in the two study groups


What are two new supportive therapies for MM?

1. Bisphosphates - inhibit bone resorption, treats bone lesions and hypercalcemia
2. Erythropoietin - helps anemia and decreases need for transfusions


What is the prognosis for Multiple Myeloma?

-Conventional chemotherapy for 3-4 years
-Intensive therapy - variable depending on age. Under 45 - 50% ten year survival
-Causes of death: marrow replacement with pancytopenia (16%), renal failure (10%), sepsis (14%), acute leukemia (5%), other chronic illnesses unrelated to myeloma (23%)