PLasma Cell disorders Flashcards
What is multiple myeloma characterized by?
neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin.
bone marrow is making cancerous blood cells which in turn is weakenng your bones
Where do plasma cells develop from?
B Lymphocytes
What do plasma cells produce?
antibodies
Where are plasma cells mainly present in?
bone marrow and lymph npdes
How do plasma cells divide?
Divide repeatedly to form a clone of many identical cells
Many clones=vast number of antibodies
What are the signs and symptoms of multiple myeloma related to?
the infiltration of plasma cells into the bone or other organs or to kidney damage from excess light chains (protein subunt that forms part of the antibody).
Is MM curable?
incurable progressive neoplasm. treatable. some pt can live up to 7 -10 years
Multiple Myeloma is highly associated with what?
Mildly associated with what?
Anemia – 73%
●Bone pain – 58%
●Elevated creatinine – 48%
Fatigue/generalized weakness – 32%
●Hypercalcemia – 28%
●Weight loss – 24%
What can the anemia be associated with in MM and what kind of anemia is it?
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Normocytic, normochromic anemia
This anemia can be related to: Bone marrow replacement Kidney damage Dilution in the case of a large M-protein B12 deficiency in 14%
Conventional radiographs abnormal 80% of patients who present with multiple myeloma. What kinds of bone disease can be present?
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- Osteopenia or osteoporosis 20%
- Focal lytic (destructive) bone 57%%- punched out lesiosns in skull for example
- Pathologic fractures 20%
- Vertebral body compression fractures 20%
These are fractures that can happen without an trauma. There must be a malignancy somewhere.
How will renal failure present in the 50% of patients that has MM?
serum creatinine is increased
What is this renal failure due to?
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- Light chain cast nephropathy (also called myeloma kidney)
- Hypercalcemia (binding of the monoclonal protein w/ calcium)
- Concurrent Light chain amyloidosis (deposition of amyloid-abnormal protein produced in marrow- that deposits in tissue)
- Drug-induced renal damage
Symptoms and signs in less than 5% of MM pts?
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paresthesias/neurologic disease hepatomegaly splenomegaly lymphadenopathy Infections CNS involvement pleural effusion & pulmonary involvement extramedullary plasmacytomas (7%) - red purple nodules or lesions
Patients suspected of having multiple myeloma (MM) should initially undergo what??
complete history and physical examination!!!!!!
The history should pay specific attention to complaints of what?
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What about the physical exam?
- bone pain,
- constitutional (the i dont feel goods) symptoms,
- neurological symptoms, and
- infections.
The physical examination should include a detailed neurologic exam
What labs would we do for MM?
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- CBC with diff, peripheral blood smear
- CMP; kidney function and calcium
- LDH
- beta-2 microglobulin (protein inc. with cell turn over)
- C-reactive protein
- Serum protein electrophoresis (SPEP) + IF Quantification of immunoglobulins
- Urinalysis and a 24-hour urine collection for electrophoresis (UPEP) + IF
- Serum free monoclonal light chain (FLC)
CBC with diff and smear beta-2 microglobulin CMP w/ kidney function and Ca LDH CRP SPEP and Ig quantifications Urinalysis + IF FLC
What would you look for on the blood smear for MM?
Rouleaux Formation!
Cell stacked like coins (elevated serum proteins level)
In an abnormal SPEP where will the spike be to indicate a positive test?
gamma globulin spike
What is monoclonal gammopathy characterized by?
disorder characterized by proliferation of a single clone of lymphoid or plasma cells
What is hyperviscoity due to in MM?
Excess protein. This protein is most likely IgM
When should serum viscosity be checked in MM?
If the M protein (IgM) is high
What three procedures should be done in patients with MM for evaluation?
- Bone marrow aspiration and biopsy with immunophenotyping
- conventional cytogenetics (function of cells in chromosomes)
- fluorescence in situ hybridization (FISH)-looks for chromosome abnormalities
What imaging should we have done with MM?
MRI, CT, or PET/CT
How would we see lytic changes in the bone that would definitely point to abnormalitites and possibly MM?
Metastatic bone survey with plain radiographs including the humeri and femoral bones should be performed in all patients
What is the pathologist looking for in a bone marrow biopsy in an MM pt?
clonal plasma cells
10% or more of clonal plasma cells
Best imaging test for MM dx?
What kind of patients would we do this in? 3
PET scan
looking for metabolic areas
–pt with compression facture or neurological deficient, or any uncertainty about the extent of the bone disease
This is an emergency
For the diagnosis of MM what needs to be present? 3
- Presence of a serum or urinary monoclonal protein
- Presence of clonal plasma cells in the bone marrow or a plasmacytoma
- Presence of end organ damage felt related to the plasma cell dyscrasia (malfunction)
What are examples of end organ damage felt related to the plasma cell dyscrasia?
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M-CRAB
Increased calcium concentration
Lytic bone lesions
Anemia
Renal failure
M-CRAB
Monoclonal protein (Lab test) Calcium Renal failure Anemia Bone marrow +/bone pain with lytic lesions
Five other types of myeloma?
Monoclonal gammopthy of undetermined significance Smouldering myeloma- Intramedullary myeloma Extramedullary myeloma Myeloma cell line
Monoclonal Gammopathy of Undetermined Significance (MGUS). What criteria must be met for diagnosis?
What would we do with this present?
- Serum monoclonal protein
Smoldering Multiple Myeloma
SMM. What criteria must be met to diagnose this?
3
- Serum monoclonal protein ≥3 g/dL
and/or
- bone marrow plasma cells ≥10 percent
- . No end organ damage related to plasma cell dyscrasia
MM: Indications for Treatment
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- Anemia (hemoglobin 11.5 mg/dL)
- Renal insufficiency (serum creatinine>2 mg/dL)
- Lytic bone lesions or severe osteopenia
- Extramedullary plasmacytoma
Maybe a FISH test looking for abnormalities in chromosome
MM: RISK STRATIFICATION
risk identification for the pt?
FISH for detection of t(4;14), t(14;16), and del17p13
Conventional cytogenetics (karyotyping) for detection of del 13 or hypodiploidy
The presence of any of the above markers defines high risk myeloma, which encompasses the 25% of MM patients who have a median survival of two years or less despite standard treatment
MM: INITIAL THERAPY
2
The initial therapy of patients with symptomatic myeloma varies depending on whether patients are eligible or not to pursue autologous hematopoietic cell transplantation
Chemo: Survival equal or less than 3 yrs
Tranplantation: 4-5 yrs (perfered but sometimes they are not a candidate for surgery)
Key issues with stem cell transplantation?
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- Efficacy compared with conventional chemotherapy
- Timing: early vs delayed (have to monitor the disease to decide when)
- Single vs tandem (hit you with one and then another)
- Role of allogeneic and miniallogeneic transplantations
- –dont use a lot of chemo proir to stem cells acquired from another person)- risk? host vs craft and relapse increase because of no chemo - Maintenance post-SCT
common: chemo followed by autologous
Could use Immunomodulatory drugs (IMiDs) to treat. What are they?2
Same with proteasome inhibitors. What are they?2
Thalidomide
Lenalidomide
Bortezomib
Carfilzomib
If a patient is clearly not a transplantation
candidate based on age, performance
score, and comorbidity what route would we take?
MPT, MPV, Len/dex
or clinical trial*
Melphalan/prednisone
Chemo drug plus steroid
If a patient is a potential transplantation
candidate for MM treatment what would we start treatment with?
- Induction therapy- reduce the number of plasma cells before we transplant
- -We would use a nonalkylator based induction X4 cycles - Then we would harvest stem cells for furture transplantation
Induction therapy may consist of one or a combination of the following types of drugs:
3
chemotherapy
targeted therapy
corticosteroids
What is waldenstrom macroglobulinemia?
is a type of non-Hodgkin lymphoma (NHL) . The cancer cells make large amounts of an abnormal protein (called a macroglobulin).
Lymphoplasmacytic lymphoma in bone marrow with an IgM monoclonal gammopathy in the blood. Usually doesnt cause that many problems. Effects are due to infiltration of hematopoietic tissues
The most common presenting features of WM include?
4
weakness, fatigue, weight loss, and chronic oozing of blood from the nose or gums
Other symptoms: ●Asymptomatic — 25% ●Constitutional symptoms — 23% ●Bleeding — 23% ●Neurologic symptoms — 22% ●Hyperviscosity (HA, vertigo, diplopia) — 31% ●Lymphadenopathy — 25% ●Hepatomegaly — 24% ●Splenomegaly — 19% ●Funduscopic abnormalities — 34%
What symptoms are due to tumor infiltration in WM?
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Anemia/Cytopenia Fever Night sweats Weight loss Lymphadenopathy Organomegaly
What symptoms are due to monoclonal IgM?
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Hyperviscosity Cryoglobulinemia Cold agglutinin Neuropathy Amyloidosis
WM: Lab Evaluation
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- Complete blood count
- Platelet function and blood coagulation
- Bone marrow examination
- Serum protein electrophoresis
- Serum viscosity
- Serum free light chain assay
- Immununofixation
- Serum ß2-microglobulin—for prognostic evaluation.
- CT
What is the criteria to diagnose WM?
3
- An IgM monoclonal gammopathy must be present in the serum.
- 10% or greater of the bone marrow biopsy must demonstrate infiltration by small lymphocytes that exhibit plasma cell differentiation
Treatment of asymptomatic WM pt with adequate hgb and platelets?
Observe, no treatment
How would we treat Symptomatic WM?
rituximab (either alone or with other agents) rather than chemotherapy alone (cyclophosphamide )
If the WM pt has a high tumor burden and meets transplant requirements what kind of transplant should they have?
hematopoietic cell transplantation (HCT)
If the patient is hyperviscous how should we treat them?
therapeutic plasmapheresis (remove affected blood from the body, take out the diseased plasma and put it back in)
