mgus (monoclonal gammopathy of unknown...
TRANSCRIPT
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The paraproteinaemias
• MGUS (Monoclonal Gammopathy of Unknown Significance)
• Multiple Myeloma:
- variant: plasmocytoma (without BM involvement)
- smoldering, extramedullary
• Waldenström macroglobulinaemia
• Amyloidosis
• Heavy chain disease
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Myeloma pathogenesis
• B-cell malignancy
• c-myc,RAS oncogen activation,cytokin-
deregulation (IL-6/IL-6R),suppressor-gene
mutation(p53), viral infection(HHV8)
• IL-6+IL-6R complex attaching membrane
gp130 result in induction of tyrosin
phosphorilation---and so the signal
transduction is initiated
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Pathogenesis of MM
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Multiple myeloma
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Disease characteristics
• Monoclonal protein production /serum and
urine samples/, elevated ESR
• Lytic bony lesions( or diffuse osteoporosis)
bone pain and fractures, hypercalcaemia
●Bone marrow involvement-cytopenia
●Renal involvement mostly of lambda light
chain production
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Protein electrophoresis in
myeloma
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Elfo Normal/ MGUS / MM
MGUS
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Characteristic laboratory alterations • Total protein 105.7 g/L H 64.0-83.0
• Albumin 27.7 g/L L 34.0-48.0
• IgG 71.59 g/L H 7.00-16.00
• IgA 0.48 g/L L 0.70-4.00
• IgM 0.27 g/L L 0.40-2.30
• Protein electrophoresis:
• M=62,89 g/L.
• A/G 0.39 - L 1.50-2.00 F
• Serum Immunfixation IgG lambda & free lambda chain
• Béta-2 mikroglobulin 8.9 mg/L H 0.9-2.0
• Kappa light chain in serum 2.91 mg/L L 6.70-22.40
• Lambda light chain in serum 1190.00 mg/L H 8.30-27.00
• Kappa Lamabda ratio in serum 0.00 - L 0.26-1.65
• Urin total protein 1379.50 mg/L H 0.00-110.00 F
• Urin total protein 1655.40 mg/24h F
• Bence-Jones protein pozitív F
• Immunfixation: monoclonal IgG lambda and free lambda chain
• We: 96 mm/h H 3-15
• RBC 3.44 Tera/L L 4.10-5.10
• Hemoglobin 97 g/L L 123-153
• Hematokrit 0.31 L/L L 0.35-0.45
MCV 91.4 fL 80.0-96.0
• Calcium 2.62 mmol/L H 2.20-2.55
• Kreatinin 61 umol/L 44-80
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Rouloux formation in MM
Check the blood smear also for circulating plasma cells!
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Scalp lytic lesions in MM
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MM in humerus
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MRI of MM involvement of vertebral
columne
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Jaw lesions might happen in myeloma causing
pain / pathological fracture upon tooth extraction
Destruction of the maxilla bone
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Durie Salmon classification of MM
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Other prognostic Indicators in
Myeloma
• Chromosome analysis (cytogenetic testing)Assesses the number and structure of chromosomes. It is evaluable only in proliferating cells. Hypoploidity is of poor prognostic significance.
• fluorescence in situ hybridization (FISH) is a test that detects abnormalities of specific chromosomes like 13/13q- wich loss is a poor prognostic marker in MM. FISH is evaluable on interphase cells
• Lactate dehydrogenase (LDH)Measures tumor-cell burden
• Plasmablastic morphologyThe general appearance of plasma cells; increased numbers of immature plasma cells (plasmablasts) indicates poor prognosis.
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Therapeutic considerations
• Overall survival: 3 yrs
1960.Gold standard : Alkeran, Prednisolon
• Others:VAD,M2,VMCP+/-Alpha interferon
From 2006.
• VEGF-INH /THALIDOMID,LENALINOMID (combination with Melphalan and prednison (response 80% 3-yr survival:74%) (side effect: neuropathy, DVT!)
• BORTESOMIB /VELCADE in combination with cyclophosphamide, melphalane, dexamtehasone ( side effect : neuropathy)
• ARSENIC TRIOXIDE
• CY/weekly, dex/monthly, low dose Thal (CR: 17%, PR: 62%)
• (OS at 2 yrs : 66%)
• ASCT( for good performance status age<65): prolongation of life: +2-3 yrs, after that inevitable recurrence of the disease.
Near future: anti CD38 Ab immunotherapy
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Supportive care
• Epo
• GM-CSF
• In hypercalcaemia: bisphosphonates,
hydration, steroid
• Allopurinol
• Irradiation
• plasmapheresis
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Primary amyloidosis causing macroglossia, infiltrating
salivary glands leading to their enlargement and
xerostomia
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Amyloid deposition in the skin
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Black-eye syndrome
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Waldenström macroglobulinaemia
• IgM monoclonality: hyperviscosity
• Fever,Hepato-splenomegaly, lymphadenopathy
• Fundus paraproteinaemicus: segmentated
dilatation of the retinal veins
• Staging: bone marrow analysis, US, CT
• Therapy: plasmapheresis,
myeloma-protocols
anti-CD20 immunotherapy
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Oral manifestations of Waldenstrom's macroglobulinaemia
• Gingival and mucosal bleeding
(spontaneous or postextraction)
• Mucosal ulcers
• Infiltration caused enlargement of the
salivary glands
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Haevy chain disease: called according to the
secreted haevy chain
• Gamma: lgl,H,S>, fever, anemia, involvement of the
Waldeyer ring - palatum-oedema
• Alpha: Mediterranean lymphoma: small intestine lamina
propria lymphoplasmocytoid infiltration- secondary
chr.diarrhoea, weight loss,mediastinal lgl↑, antibiotic
therapy might be effective in the begining
• μ(mű): frequent association to CLL, κ (kappa) light chain
in the urine, vacuolizated lymphocytes in the smear