Multiple Myeloma (Definition/Incidence)

MULTIPLE MYELOMA
(DEFINITION/INCIDENCE)
PATHOGENESIS OF MULTIPLE MYELOMA
MULTIPLE MYELOMA
(CLINICAL FEATURES)
• Neoplasm of terminally differentiated B lymphocytes called plasma cell
• plasma cell accumulation in the bone marrow
• the presence of monoclonal protein (M-protein) in the serum or urine (light chain component, large cant pass
glomerular, after urine overwhelmed, paraprotein accumulate in plasma)
• tissue damage
• hypercalcemia
• Renal problem
• Anemia
• Bone pain
• 98% after age 40 y/o
• Peak 65-70%
1. MGUS develops as a result of abnormal response to antigenic stimulation. Leads to Primary cytogenetic
abnormality
• Ig heavy chain gene translocation ( chromosome 14) with D-cyclin gene
• Deletion of chromosome 13
• hyperdiploidy
2. Random second hit dependent conversion

• Due to Genetic lesion (RAS mutations, secondary translocation)
3. Which forms Myeloma cells with end organ damage.

• Plasma cell infiltration to BM
• Kidney damage from excessive light chain.
1. Bone pain (vertebral compression fracture, lytic bone lesion) – MM secretes cytokines – inhibit osteoblast, stimulate
osteoclast
2. hypercalcemia
3. Renal failure – light chain cast in renal tubules
4. Anemia – plasma cell infiltration in BM
5. Recurrent Infection – hypogammaglobulinermia
6. Hemorrhage tendency – Ig coats plt interfering aggregation.
7. Hyperviscocity syndrome – high paraprotein – triade (visual change, bleeding, neurology)

MULTIPLE MYELOMA
(LAB FEATURES)
MULTIPLE MYELOMA
(STAGES OF PROGRESSION)
MULTIPLE MYELOMA
(STAGING – REVISED INTERNATIONAL STAGING SYSTEM - RISS)
• FBC - NCNC anemia, leukopenia, thrombocytopenia
• FBP – Rouleaux formation.
• Biochem – RP, LFT, Ca, ESR, serum B2 microglobulin, LDH
• Serum quantitative Ig – measure amount of different Ig (60% IgG, 20% IgA, 1% IgD/IgE, 20%light chain)
• Serum/Urine protein electrophoresis (SPEP) – paraprotein appear as large peak
• Immunofixation – types of Ig and heavy/light, kappa/lambda
• Serum free light chain quantification – abnormal kappa:lambda (normal 0.6, range 0.26-1.65)
• BM – increased plasma cell immunophenotyped with anti CD138. (>10%clonal plasma cells)
• Xray – bone survey
• MRI of spine, CT, PET – myeloma bone disease
• Cytogenetics – aneuploidy, translocation.

MULTIPLE MYELOMA
(TREATMENT)
MULTIPLE MYELOMA
(DRUGS SIDE EFFECT)
MULTIPLE MYELOMA
(TREATMENT – SUPPORTIVE CARE)
• COMBINATION OF 2-3 DRUGS
• BORTEZOMIB
• DEXAMETHASONE
• THALIDOMIDE
• LENALIDOMIDE
• CYCLOPHOSPHOMIDE
• NEW DRUGS
• POMALIDOMIDE
• CARFILZOMIB
MULTIPLE MYELOMA
(PROGNOSIS)
MULTIPLE MYELOMA
(PLASMACYTOMA OF BONE DIAGNOSIS)
MULTIPLE MYELOMA
(POEMS SYNDROME)
• median survival – 7- 10 years
• younger patient (<50 years old) can be > 10 years
• Poor prognosis when

• High LDH.
• hypodiploidy
• ≥4% plasma cells in the peripheral blood.
• Beta 2 Microglobulin(β2M) level: reflects tumor load, renal function , disease activity and drug sensitivity.
• CRP: Reflect IL-6 activity.
• Combination of β2M & CRP allows classification into three groups.

• Low-risk group with both CRP and β2M < 6 mg/L
• Intermediate-risk group with CRP or β2M < 6 mg/L
• High-risk group with CRP and β2M ≥ 6 mg/L.
• Favourable when
• Hyperdiploidy
• No adverse FISH lesion
• Biopsy-proven solitary tumor of bone with evidence of clonal plasma cells
• Metastatic bone survey and either CT or MRI of the spine and pelvis must show no other lytic lesions.
• BMAT must contain no clonal plasma cells.
• There is no anemia, hypercalcemia, or renal insufficiency that could be attributed to a clonal plasma cell proliferative disorder.
• The presence of a monoclonal (M) protein does not exclude the diagnosis of SPB,
• Treatment
• Radiotherapy
• Mostly progressed to MM
• Polyneuropathy
• Organomegaly, lymphadenopathy
• Endocrinopathy
• M protein
• Skin changes
• Must have M protein with monoclonal lambda light chain, bone lesion, plasma cell in BM<20%
MULTIPLE MYELOMA
(AMYLODOISIS)
MULTIPLE MYELOMA
(WALDENSTORM MACROGLOBULINEMIA)
• Deposition of monoclonal light chains produced from a clonal plasma cell proliferation.
• Complication
• restrictive cardiomyopathy,
• kidneys
• Tongue
• Gastrointestinal tract
• peripheral nerves and autonomic nervous system
• Ix - A serum amyloid P (SAP) scan is used to determine the extent and severity of disease.
• Treatment
• chemotherapy, possibly with autologous SCT,
• M-protein is IgM
• IgM higher molecular weight, confined to vascular space
• Hyperviscocity syndrome
• Big molecule does not cause renal impairment.
• BM infiltration with lympho-plasmacytoid cells
• lymphoplasmacyticlymphoma+ macroglobulinaemia= WM
• Clinical Features
• More in male + median age:63 years.
• Lymphadenopathy or hepato-splenomegaly.
• Bleeding caused by platelet dysfunction or clotting abnormalities.
• Hyperviscosity syndrome.

Multiple Myeloma (Definition/Incidence)

Uploaded by

Copyright:

Available Formats

Multiple Myeloma (Definition/Incidence)

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Multiple Myeloma (Definition/Incidence)

Uploaded by

Copyright:

Available Formats

MULTIPLE MYELOMA

PATHOGENESIS OF MULTIPLE MYELOMA

• plasma cell accumulation in the bone marrow

• 98% after age 40 y/o

2. Random second hit dependent conversion

3. Which forms Myeloma cells with end organ damage.

3. Renal failure – light chain cast in renal tubules

4. Anemia – plasma cell infiltration in BM

5. Recurrent Infection – hypogammaglobulinermia

6. Hemorrhage tendency – Ig coats plt interfering aggregation.

7. Hyperviscocity syndrome – high paraprotein – triade (visual change, bleeding, neurology)

• FBP – Rouleaux formation.

• Biochem – RP, LFT, Ca, ESR, serum B2 microglobulin, LDH

• Serum/Urine protein electrophoresis (SPEP) – paraprotein appear as large peak

• Immunofixation – types of Ig and heavy/light, kappa/lambda

• Xray – bone survey

• MRI of spine, CT, PET – myeloma bone disease

• Cytogenetics – aneuploidy, translocation.

• Poor prognosis when

• Combination of β2M & CRP allows classification into three groups.

• Biopsy-proven solitary tumor of bone with evidence of clonal plasma cells

• BMAT must contain no clonal plasma cells.

• BM infiltration with lympho-plasmacytoid cells

You might also like

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.