multiple myeloma - semantic scholarpdfs.semanticscholar.org/presentation/8f59/...myeloma-...
TRANSCRIPT
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Multiple Myeloma
Brian Berryman, M.D.Brian Berryman, M.D.
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Myeloma- Introduction
•• A clonal disorder of plasma cells (BA clonal disorder of plasma cells (B--cells).cells).•• Affects 1 in 300,000. Affects 1 in 300,000.
–– 1% of all new malignancies (16,000 per year)1% of all new malignancies (16,000 per year)–– 10% of all new hematologic malignancies10% of all new hematologic malignancies–– 2% of all cancer deaths (11,300 per year)2% of all cancer deaths (11,300 per year)
•• Median age of onset: 66 Median age of onset: 66 •• Most common hematologic malignancy in Most common hematologic malignancy in
African Americans.African Americans.
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Myeloma- Introduction
•• Survival:Survival:–– PrePre--chemotherapy: 7 monthschemotherapy: 7 months–– Current: 24Current: 24--30 months +30 months +
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Myeloma- Risk Factors
•• No specific etiologic agentNo specific etiologic agent•• Risk factors include:Risk factors include:
–– Ionizing radiation.Ionizing radiation.–– Chronic Antigenic Stimulation.Chronic Antigenic Stimulation.–– Environmental. Environmental.
•• BenzeneBenzene•• Hair dyesHair dyes
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Symptoms
•• Fatigue.Fatigue.•• Bone pain.Bone pain.•• Recurrent infections. Recurrent infections.
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Diagnostic Work-up•• History and physicalHistory and physical•• CBC with differentialCBC with differential•• Chemistry panel to include: Chemistry panel to include: CreatinineCreatinine, calcium , calcium
and albumin and albumin •• SPEP/IFE SPEP/IFE •• UPEP/IFE (24 hour)UPEP/IFE (24 hour)•• Quantitative Quantitative immunoglobulinsimmunoglobulins•• BetaBeta--22 microglobulinmicroglobulin•• Bone marrow examinationBone marrow examination•• Skeletal surveySkeletal survey
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Diagnostic Work-up
•• Serum free light chain measurement Serum free light chain measurement (especially in light chain, (especially in light chain, oligooligo--secretory secretory and nonand non--secretory secretory disease)disease)
•• LDH LDH •• CRP CRP •• Myeloma FISH panel on bone marrowMyeloma FISH panel on bone marrow•• MRIMRI•• PETPET
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Hypercalcemia
•• Occur in a third of patients.Occur in a third of patients.•• Symptoms: bony pain, polydipsia/ polyuria, Symptoms: bony pain, polydipsia/ polyuria,
confusion, and constipationconfusion, and constipation•• May be precipitated by dehydration or intravenous May be precipitated by dehydration or intravenous
contrastcontrast•• Treat with vigorous hydration, diuresis, Treat with vigorous hydration, diuresis,
bisphosphonates, and steroidsbisphosphonates, and steroids
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Skeletal Manifestations
•• Occur in >70% patientsOccur in >70% patients–– Multiple 70%Multiple 70%–– Isolated lesion or diffuse osteopenia 15%Isolated lesion or diffuse osteopenia 15%–– Normal 15%Normal 15%
•• BlasticBlastic lesions in <2%.lesions in <2%.
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Renal Manifestations
•• Elevated Elevated creatinine creatinine in 50%in 50%•• Myeloma kidneyMyeloma kidney-- usually LC diseaseusually LC disease•• AmyloidAmyloid with nonspecificwith nonspecific proteinuriaproteinuria..•• Caution with Caution with NSAIDsNSAIDs and IV contrastand IV contrast•• HYDRATION!HYDRATION!
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Blood Smear
Rouleaux
Plasma cell leukemia
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SPEP/IFE
IgD λ myeloma
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Bone Survey
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PET Scan
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Definitions
•• MGUSMGUS-- Monoclonal gammopathy of Monoclonal gammopathy of unclear significanceunclear significance–– MM--protein < 3 g/dL protein < 3 g/dL –– Plasma cells in bone marrow <10%Plasma cells in bone marrow <10%–– No related organ or tissue impairment (CRAB)No related organ or tissue impairment (CRAB)
–– May evolve to Multiple Myeloma (20% in 8May evolve to Multiple Myeloma (20% in 8--10 10 years)years)
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Definitions
•• “CRAB”“CRAB”–– CalciumCalcium–– Renal insufficiencyRenal insufficiency–– AnemiaAnemia–– Bone lesionsBone lesions
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Definitions
•• Smoldering or Indolent Multiple MyelomaSmoldering or Indolent Multiple Myeloma–– MM--protein protein ≥≥ 3 g/dL3 g/dL–– Plasma cells in bone marrow Plasma cells in bone marrow ≥≥ 10%10%–– MM--protein in urineprotein in urine–– No related organ or tissue impairment (CRAB)No related organ or tissue impairment (CRAB)
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Definitions
•• Symptomatic Multiple MyelomaSymptomatic Multiple Myeloma–– MM--protein in blood and/or urineprotein in blood and/or urine–– Bone marrow clonal plasma cells or Bone marrow clonal plasma cells or
plasmacytomaplasmacytoma–– Related organ or tissue impairment or Related organ or tissue impairment or
symptomssymptoms
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Staging Low burden (<0.6 x 10Low burden (<0.6 x 101212))-- All below:All below:
-- HB > 10 g/dlHB > 10 g/dl -- Ca<12 mg/dlCa<12 mg/dl -- IgG < 5g/dlIgG < 5g/dl -- IgA < 3 g/dlIgA < 3 g/dl -- UPEP M < 4 g/24 hrsUPEP M < 4 g/24 hrs -- Normal Xrays or solitary plasmacytomaNormal Xrays or solitary plasmacytoma
Intermediate (0.6Intermediate (0.6--1.2 x 101.2 x 101212)) -- Neither I nor IIINeither I nor III
High Tumor burden (>1.2)High Tumor burden (>1.2)-- ANY of:ANY of: -- HB < 8.5HB < 8.5 -- Ca >12Ca >12 -- IgG >7 g/dlIgG >7 g/dl -- IgA > 5 gm/dlIgA > 5 gm/dl -- UPEP M > 12 g/24UPEP M > 12 g/24 -- Extensive bony diseaseExtensive bony disease
Stage I
Stage II
Stage III
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Myeloma- Natural History
•• 90% cases are disseminated and 90% cases are disseminated and progressive, 3% indolent and 7% localizedprogressive, 3% indolent and 7% localized
•• Clinical course and symptoms relate to:Clinical course and symptoms relate to:–– Occurrence and locations plasmacytomasOccurrence and locations plasmacytomas–– Impairment hematopoeisisImpairment hematopoeisis–– Skeletal disease (bony, Ca++)Skeletal disease (bony, Ca++)–– Protein abnormalities (viscosity, low nl Ig, Protein abnormalities (viscosity, low nl Ig,
amyloid, renal, neuropathy)amyloid, renal, neuropathy)
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Plasmacytomas
•• Skeletal or extraskeletal (sinus, Skeletal or extraskeletal (sinus, nasopharynx)nasopharynx)
•• Prognosis of localized ~8 yearsPrognosis of localized ~8 years•• ExtraskeletalExtraskeletal better prognosis.better prognosis.•• Skeletal lesions disseminate in ~3 yearsSkeletal lesions disseminate in ~3 years
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Prognostic Factors
•• Performance status Performance status •• StageStage•• Cytogenetics Cytogenetics •• LDHLDH•• PlasmablasticPlasmablastic variants/Plasma cell leukemiavariants/Plasma cell leukemia
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