MM and Plasma Cell Disorders Flashcards
What are the etiologies and risk factors of Multiple Myeloma?
Age, African American race, first-degree relative, exposure to radiation, pesticides, cleaners, military, autoimmune or inflammatory disorders, and possibly infections.
What is the underlying pathology of Multiple Myeloma?
Malignant proliferation of a single clone of plasma cells producing an abnormal amount of M Protein.
What are the presenting signs and symptoms of Multiple Myeloma?
Bone pain, vertebral compression fractures, weakness, fatigue, recurrent or serious infections.
What diagnostic studies are appropriate for Multiple Myeloma?
CBC with differential, peripheral smear, CMP, LDH, β2 microglobulin, serum protein electrophoresis, serum immunofixation electrophoresis, quantitative immunoglobulins, 24-hour urine for electrophoresis and immunofixation, serum free light chains.
What are the major criteria for diagnosing POEMS syndrome?
Polyneuropathy, Monoclonal Plasma cell disorder, Sclerotic bone lesions, Castleman disease, VEGF elevation
What is the purpose of serum PEP and IEP tests?
To detect the presence of an M-spike in the gamma region.
How is Multiple Myeloma staged and risk stratified?
Based on laboratory findings, imaging studies, and clinical presentation.
How many major criteria are required to diagnose POEMS syndrome?
Three
What are the treatment modalities for Multiple Myeloma?
Chemotherapy, stem cell transplant, radiation therapy, targeted therapy, immunotherapy.
What does IEP stand for?
Immunofixation electrophoresis.
What is a common feature of Castleman disease in POEMS syndrome?
Lymph node hyperplasia
What are the adverse effects of Multiple Myeloma treatments?
Nausea, fatigue, infections, bone marrow suppression, neuropathy.
Why is a 24-hour urine collection required for PEP and IEP?
To detect Bence-Jones Protein, an Ig or light chain found in the urine.
What does VEGF stand for in the context of POEMS syndrome?
Vascular endothelial growth factor
What is a higher rate of neutropenia associated with?
Lenalidomide and Dexamethasone (RD)
What are plasma cells?
B lymphocytes that mature and produce antibodies for humoral immunity.
What requires ASA prophylaxis?
Lenalidomide and Dexamethasone (RD)
Why are UPEP and UIEP tests done along with serum tests?
20% of patients only produce free light chains, which may not be detectable in serum.
What is one of the minor criteria for diagnosing POEMS syndrome?
Organomegaly, ECF volume overload, Endocrine disorder, skin changes, papilledema, thrombocytosis/polycythemia
What increases the sensitivity of detecting free light chains?
Serum free light chains.
What are the side effects of Bortezomib and Dexamethasone (VD)?
Peripheral neuropathy, HSV reactivation
What are immunoglobulins?
Antibodies produced by plasma cells, also known as gammaglobulins.
What are the heavy chain isotypes of immunoglobulins?
G, M, A, D, E.
What imaging study is used to evaluate for lytic lesions?
Skeletal survey with plain films.
What is the clinical course of POEMS syndrome often defined by?
Progressive polyneuropathy
What prophylaxis is required for Bortezomib and Dexamethasone (VD)?
HSV prophylaxis
Why is a bone scan not used for lytic lesions?
Radioisotope is not taken up by lytic lesions.
Why is the diagnosis of POEMS syndrome often delayed?
It is often confused with other neurologic diseases.
What are the light chain isotypes of immunoglobulins?
Kappa (κ) and lambda (λ).
What are the components of the CyBorD regimen?
Cyclophosphamide, Bortezomib, and Dexamethasone
What can MRI detect in multiple myeloma?
More lesions and assess for spinal cord compression.
What is hypogammaglobulinemia?
Low levels of antibodies.
What are the components of the VRD regimen?
Bortezomib, Lenalidomide, and Dexamethasone
What is monoclonal gammopathy?
Disease involving a single antibody clone.
What is used for pain control in plasmacytomas or lytic lesions?
Radiation
What are plasma cell disorders?
Monoclonal neoplasms arising from uncontrolled maturation and proliferation of antibody-secreting B-lymphocytes.
Why is PET often preferred in combination with a skeletal survey?
Increased uptake with lytic lesions.
What can neuropathy in POEMS syndrome progress to?
Respiratory compromise
What is the treatment for POEMS syndrome aimed at?
Underlying plasma cell disorder
What treatment has shown significant or complete resolution of symptoms in POEMS syndrome?
Autologous SCT
What is used to treat hypercalcemia?
Bisphosphonates
What is the role of CT in multiple myeloma?
Characterization of soft tissue masses/plasmacytomas.
What resource is known as a comprehensive guide for internal medicine and is useful for POEMS syndrome?
Harrison’s Principles of Internal Medicine
What is required for the diagnosis of lytic lesions?
Bone marrow biopsy.
What are some examples of plasma cell disorders?
Multiple Myeloma, MGUS, Waldenstrom’s macroglobulinemia, primary amyloidosis.
What was the 5-year survival rate for all ages and sexes in 1975 according to SEER data?
26.6%
What does a bone marrow biopsy quantify and characterize?
Plasma cells.
What is Multiple Myeloma?
A malignant proliferation of a single clone of plasma cells producing an abnormal amount of M Protein.
What is the purpose of flow cytometry in multiple myeloma?
Immunophenotyping to differentiate normal from malignant plasma cells.
Which resource provides current medical diagnosis and treatment information relevant to POEMS syndrome?
Current Medical Diagnosis & Treatment
What online resource is mentioned for up-to-date information on POEMS syndrome?
Up to Date
What do cytogenetics and karyotyping help determine in multiple myeloma?
Risk and prognosis.
What was the 5-year survival rate for all ages and sexes from 2006-2012 according to SEER data?
48.1%
What is M protein in Multiple Myeloma?
Monoclonal protein that may be intact immunoglobulin or fragments of heavy or light chains.
What was the 5-year survival rate for all ages and sexes from 2012-2018 according to SEER data?
57%
What are the three criteria required for diagnosing symptomatic multiple myeloma?
Any level of M-protein in serum/urine, bone marrow biopsy with >10% plasma cells or biopsy-proven plasmacytoma, and evidence of organ/tissue involvement (CRAB criteria).
What does SEER stand for?
Surveillance, Epidemiology, and End Results Program
What does CRAB stand for in the context of multiple myeloma?
Hypercalcemia, renal disease, anemia, bone disease.
What does ‘multiple’ in Multiple Myeloma refer to?
Bony lesions in multiple sites at the time of diagnosis.
What is a plasmacytoma?
Proliferation of plasma cells outside the bone marrow.
What happens in Plasma Cell Leukemia?
Plasma cells exit BM and enter peripheral bloodstream
What is the International Staging System (ISS) used for?
Staging multiple myeloma based on albumin and B2-macroglobulin levels.
What percentage of patients are affected by Plasma Cell Leukemia?
~1%
What are the most common subtypes of Multiple Myeloma?
IgG (60%) and IgA (20%).
What are the albumin and B2-macroglobulin levels for Stage I multiple myeloma?
B2M ≤ 3.5 mg/L, albumin ≥ 3.5 g/dL.
What is the median survival for Stage I multiple myeloma?
62 months.
How is Plasma Cell Leukemia reported?
On CBC with Differential as % Plasma cells
What defines Stage II multiple myeloma?
Neither Stage I nor III criteria are met.
What is the epidemiology of Multiple Myeloma?
More common in males, median age 69, African American > Caucasian 2:1.
What does the presence of plasma cells on a peripheral smear indicate?
Poorer prognosis
What is the median survival for Stage II multiple myeloma?
44 months.
What are the risk factors for Multiple Myeloma?
Age, African American race, first-degree relative, exposure to radiation, pesticides, cleaners, military, autoimmune or inflammatory disorders, possibly infections.
What are the B2-macroglobulin levels for Stage III multiple myeloma?
B2M ≥ 5.5 mg/L.
What are other plasma cell disorders mentioned?
Waldenstrom Macroglobulinemia, Amyloidosis, POEMS syndrome
What is the median survival for Stage III multiple myeloma?
29 months.
What are common symptoms of Multiple Myeloma?
Bone pain, vertebral compression fractures, weakness, fatigue, recurrent or serious infections.
What is another name for Waldenstrom Macroglobulinemia?
Lymphoplasmacytic Lymphoma
What type of cells are involved in Waldenstrom Macroglobulinemia?
Mature B lymphocytes undergoing plasmacytic differentiation
What is smoldering multiple myeloma?
Asymptomatic multiple myeloma with M protein ≥ 3g/dL or BM plasma cells ≥ 10%, no CRAB criteria.
What are common physical exam findings in Multiple Myeloma?
Often normal, anemia (pallor), extramedullary plasmacytomas, palpable masses, point tenderness at fracture sites.
What is the expected progression time for smoldering multiple myeloma to symptomatic multiple myeloma?
4-5 years.
What do the cells in Waldenstrom Macroglobulinemia produce?
Monoclonal IgM
What is MGUS?
Monoclonal gammopathy of undetermined significance, a pre-malignant condition.
What are the criteria for MGUS?
M protein < 3g/dL, bone marrow plasma cells <10%, no CRAB criteria.
Is treatment indicated for smoldering multiple myeloma or MGUS?
No.
What laboratory evaluations are used for Multiple Myeloma?
CBC with differential, peripheral smear, CMP, LDH, β2 microglobulin, serum protein electrophoresis, serum immunofixation electrophoresis, quantitative immunoglobulins, 24-hour urine for electrophoresis and immunofixation, serum free light chains.
What are the common presentations of Waldenstrom Macroglobulinemia?
Anemia, Lymphadenopathy, splenomegaly, hyperviscosity
What is the expected survival without treatment for symptomatic multiple myeloma?
~6 months.
What is usually absent in Waldenstrom Macroglobulinemia?
Lytic lesions
How much can chemotherapy or transplant increase survival in symptomatic multiple myeloma?
2-5+ years.
What are common laboratory findings in Multiple Myeloma?
Anemia, renal dysfunction, hypercalcemia, hyperproteinemia, hypogammaglobulinemia, Rouleaux formation on peripheral smear.
What are the symptoms of hyperviscosity in Waldenstrom Macroglobulinemia?
Vision changes, HA, dizziness, cardiopulmonary symptoms, bleeding
How is the response to treatment monitored in multiple myeloma?
By reduction of M protein in serum/urine and size of plasmacytomas.
What is Rouleaux formation?
Stacking of RBCs related to increased serum protein levels.
Is there a cure for multiple myeloma?
No, treatment is for disease control, palliation, and prolonging survival.
How is hyperviscosity treated in Waldenstrom Macroglobulinemia?
Plasmapheresis
What is the work-up for Waldenstrom Macroglobulinemia similar to?
Multiple Myeloma
What is the frontline treatment for multiple myeloma?
Autologous stem cell transplantation with high-dose melphalan chemotherapy.
What is the significance of serum protein electrophoresis (SPEP) in Multiple Myeloma?
Used to confirm the type of hyperproteinemia and detect M-spike in the gamma region.
What is the treatment approach for asymptomatic Waldenstrom Macroglobulinemia?
Observation
What is immunofixation electrophoresis (IEP)?
A technique to identify specific types of immunoglobulins in the serum.
What is the benefit of autologous stem cell transplantation over chemotherapy alone?
Significant survival benefit.
What precedes autologous stem cell transplantation?
2-4 cycles of chemotherapy to reduce disease burden.
What are the treatment indications for Waldenstrom Macroglobulinemia?
Hyperviscosity, Hgb <10 g/dL, Platelet <100K, Bulky adenopathy or symptomatic organomegaly, Neuropathy
What factors determine eligibility for autologous stem cell transplantation?
Co-morbidities and age (Performance Status).
What is the treatment for Waldenstrom Macroglobulinemia?
Rituximab +/- combination chemotherapy, Autologous SCT after disease control if eligible
What is tandem transplantation?
Two transplants 3-6 months apart.
When might an allogeneic transplant be required?
Depending on risk and response to autologous transplant.
What is another name for Amyloidosis?
Systemic Light-Chain Amyloidosis
What are the components of the RD treatment regimen?
Lenalidomide and dexamethasone.
What are the side effects of the RD regimen?
Higher rate of neutropenia and VTE, requires ASA prophylaxis.
What is deposited in organs in Amyloidosis?
Residues of light-chains (amyloid fibrils)
What are the components of the VD treatment regimen?
Bortezomib and dexamethasone.
What are the side effects of the VD regimen?
Peripheral neuropathy and HSV reactivation, requires HSV prophylaxis.
What are the components of the CyBorD treatment regimen?
Cyclophosphamide, bortezomib, and dexamethasone.
What are the components of the VRD treatment regimen?
Bortezomib, lenalidomide, and dexamethasone.
What percentage of Amyloidosis cases involve lambda light chains?
75%
What percentage of patients with Multiple Myeloma have Amyloidosis?
10-15%
What does the presentation of Amyloidosis depend on?
Organ involvement
What are the renal symptoms of Amyloidosis?
Renal insufficiency, nephrotic syndrome
What are the cardiac symptoms of Amyloidosis?
Cardiomyopathy, arrhythmia
What are the nervous system symptoms of Amyloidosis?
Peripheral neuropathy, weakness, orthostatic hypotension, ED, anhidrosis
What are the gastrointestinal symptoms of Amyloidosis?
Hepatomegaly, GI bleeding, diarrhea, malabsorption
How is Amyloidosis diagnosed?
Biopsy of abdominal fat pad or organ involved, Congo Red stain, mass spectrometry analysis
What does Congo Red stain show in Amyloidosis?
Positive apple-green birefringence on polarized light exam
What is the treatment goal for Amyloidosis?
Preventing further deposition
What is the treatment for Amyloidosis?
High-dose chemotherapy + Autologous Stem Cell Transplant
What is the prognosis for Amyloidosis with organ involvement?
Poor, particularly with cardiac involvement
What is POEMS syndrome associated with?
Plasma cell disorder (typically Myeloma)
What does POEMS stand for?
Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, Skin Changes
How many major criteria are required for POEMS syndrome diagnosis?
3
What are the major criteria for POEMS syndrome?
Polyneuropathy, Monoclonal Plasma cell disorder, Sclerotic bone lesions, Castleman disease, VEGF elevation
How many minor criteria are required for POEMS syndrome diagnosis?
One
What are the minor criteria for POEMS syndrome?
Organomegaly, ECF volume overload, Endocrine disorder, skin changes, papilledema, thrombocytosis/polycythemia
