Multiple Myeloma Flashcards
lymphoid stem cell development
Lymphoid cells
T cells, B cells, plasma cells, NK cells
Monoclonal AB
MAde by 1 clone of plasma cells or lymphocytes
- consists of 1 class of heavy chain and 1 type of light chain (kappa or lambda)
Multiple myeloma
overview
proliferation of neoplastic plasma cells
cells are clinal and have monoclonal antibody production
high levels of this antibody found in blood and urine
Proliferation of plasma cells leads to:
1. crowding out of normal marrow cells
- pancytopenia, anemia, infections (mostly encapsulated bacteria), bleeding
2. bone lesions
- tumor growth + bone resorption
- Cells make IL-1 and other bone resortion factors
- “punched out” osteolytic lesions on xray
- bone pain, pathologic fractures
- hypercalcemia
3. increased cell turnover
- uric acid and calcium phosphate deposits
Criteria for MM dx
- monoclonal plasma cells in bone marrow
- monoclonal protein present in serum and/or urine
- myeloma- related organ disfucntion
Calcium high in serum
Renal insufficiency
Anemia
Bone lesions or osteoporosis
Monoclonal AB production leads to:
- elevated serum protein (hyperviscosity)
- Hyperglobulinemia
- but effective hypoglobulinemia and increased infections - monoclonal spike on protein electrophoreisis
- Rouleaux formation of RBcs on smear
- RBCs stick together
5. excess light chains
- in urine and serum
- renal failure and amyloidosis
6. ** ABs coat coag factors** - may see bleeding
Multiple myleoma types
IGG— MOST COMMON, CLASSIC FINDINGS
IGM— HYPERVISCOSITY, USUALLY WALDENSTROMS
IGA —MAY HAVE “FLAME CELLS” (SECRETORY PART)
IGD— RARE, MAY MISS ON IEP (NEED ANTI-D)
IGE— RARE. MAY PRESENT WITH PC LEUKEMIA
LIGHT CHAIN ONLY— (HYPOGLOBULINEMIA ON SPEP, +UPEP)
NULL— (NO SECRETION OF AB BUT HAVE NEOPLASTIC PROLIF OF
PLASMA CELLS IN MARROW, USUALLY HYPOGLOBULINEMIC)
- Plasmacytoma
- plasma cell leukemia
- isolated collection of plasma cells, plasma cell tumor
- neoplastic plasma cell in blood
Distribution of monoclonal proteins in MM
M protein found in serum or urine of 97% at time of dx
Myeloma clinical findings
Pathologic fractures
pancytopenias
renal failure
hyperviscosity
Myeloma causes increased infections due to:
- lack of effective antibodies
- decreased opsonization
- neutropenia from marrow myeloma
- chemotherapy
steroids-> immunosuppression
neutropenia
Myeloma renal failure due to
- myeloma kidney: light chains inhibit renal tubular function
- amymoidosis: light chain deposits
- uric acid and calcium deposits (hyper ca and hyper uric acid)
- renal infiltrates by plasma cells
- infections: pylenephritis, glomerulonephritis
Tx for myeloma
1. Bisphosphonates
- supportive and adjunctive therapy for MM
2. Immunomodulatory drugs
- thalidomide, lenalidomide
- disrupts cell-cell, vascular interaction, microenviroment and indirectly supresses neoplasm
3. Proeosome inhibitors
- Bortesomib
- potent, possible directed against nf-kb in myeloma cell
4. stem cell transplant
- others- (ex. phenylalanine mustard, HSP90 inhibitors)
Waldenstroms macroblobulinemia
- lymphoid-plasmacytoid cells in marrow and sometimes blood
- clonal production of igM
- IgM pentamers, large, in plasma lead to hyperviscosity
- sypmptoms from hyperviscosity
- fatigue, malaise, SOB, neurologic, bleeding, headache, visual symptoms - No bone lesions
- early lymphocytoi-plasma cells dont made bone resorption factors