1. Epidemiology 12,000 deaths in United States per year
Median age of diagnosis is 65 years
Two-fold more common in African-Americans than Caucasians
Higher incidence in men than women
Median survival is three years

2. Diagnosis CBC, CMP, Uric Acid SPEP, UPEP, Immunofixation
Quantitative Ig’s
Skeletal survey
Bone marrow aspirate and Trephine biopsy
Cytogenetics

3. Diagnostic Criteria Durie and Salmon
Major criteria-- >30% plasma cells in BM or
biopsy proven plasmacytoma,
M spike of >3.5 IgG, 2.0 IgA or
>1 g/24h in urine
2. Minor criteria BM with 10-30% plasma cells,
M-component of serum or urine less than
above,
lytic lesions,
Normal IgM <500 mg/L, IgA<1g/L and
IgG<6g/L
Need at least one major and one minor or three minor including +BM and M spike.

4. Classical Diagnostic Features of Myeloma
Plasmacytosis in marrow
Monoclonal protein in serum or urine
Lytic disease of bone

5. Marrow Plasmacytosis in Myeloma
Plasma cells > 10%
Usually much higher
Often present in ‘sheets’
Alternatively, biopsy-proven plasmacytoma
Other causes of plasmacytosis:
inflammation, cirrhosis, AIDS

6. Diagnosis of Myeloma: Monoclonal Proteins
75-80% have serum monoclonal Ig
(M-component, paraprotein, or ‘spike’ on electrophoresis)
10-20% make light chains only → rapid renal excretion → serum paraprotein absent
→ do urine electropheresis
Non-secretory myeloma rare (<1%)
Other causes of monoclonal proteins
CLL, lymphoma
Autoimmune disease, infection
Benign monoclonal gammopathy

10. Bone Disease in Myeloma
Unbalanced osteoclast activity
Radiographic manifestations
- Osteoporosis almost invariable
- Usually multiple lytic lesions
- Axial skeleton involved (active marrow)
- Osteoblastic reaction minimal
Hypercalciuria and hypercalcemia

11. Benign Monoclonal Gammopathy
Monoclonal Ig as isolated finding
More common than myeloma
No bone disease, anemia, renal dysfunction
Most remain stable
About 10% eventually develop classical myeloma

12. Clinical Features of Myeloma at Presentation
Early – asymptomatic, incidental diagnosis
Paraprotein on electropheresis
Mild marrow plasmacytosis
Solitary plasmacytoma (10% of cases)
Late – symptomatic
Bone pain (usually lower back)
Pneumococcal infection
Systemic symptoms (e.g. weakness, weight loss)
Related to anemia, renal failure, hypercalcemia

13. Hyperviscosity Syndrome
Due to aggregating paraprotein
Pathogenesis
- Circulatory insufficiency, abnormal hemostasis
Manifestations
- Bleeding
- Dyspnea (congestion on CXR)
- Encephalopathy and visual disturbances

14. Immunological Features of Myeloma
Monoclonal Ig and/or monoclonal light chain
↓ levels of normal Ig’s (functional hypogammaglobulinemia)
Cellular immune responses usually preserved
Bacterial infections common
Early: S pneumoniae
Late: S aureus, Gram negative rods

15. Amyloidosis in Myeloma
Due to light chain deposition in tissues
Incidence: λ amyloid > K amyloid
Organs commonly involved:
Skin
Tongue and GI
Heart
Peripheral nerves
Kidneys
Soft tissues
No effective therapy, except ? Stem cell transplant

16. Therapy for Myeloma Biphosphonates (pamidronate, zoledronate)
Radiotherapy
Conventional dose chemotherapy
Alkylators and corticosteroids
Thalidomide
Myeloablative therapy and stem cell transplantation
Autografting → survival improved, but relapse inevitable
Allografting → cure is possible, but transplant-related mortality is high

17. Differential diagnosis of myeloma and monoclonal gammopathy of undetermined significance (MGUS)
Bone marrow plasma cells
>10% on aspirate
<10% on aspirate
Serum paraprotein
Variable concentration in serum:
no specific diagnostic levels
IgG usually <20 g/l
IgA usually <10 g/l
Bence-Jones proteinuria
>50% cases
Rare
Immune paresis
>95% cases
Lytic bone lesion
Often present
Absent
Symptoms
Frequent
Anaemia
Hypercalcaemia
May be present
Abnormal renal function

18. Stage I—Hb>10. Ca<12. NI bones or solitary plasmacytoma of bone only. Low M-component production (IgG<5, <4g/24 hours) urine light chain.
Stage II—Not I or III
Stage III-Hb<8.5, Ca>12. Advanced lytic lesions. High M-component production.

19. Staging Subclassification
A = Cr<2
B= Cr>2
Prognosis also predicted adversely by high Beta 2 microglobulin, chr 13 deletions

20. Indications for Therapy
Management of symptomatic myeloma or radiographic evidence of bone disease
Chemo is not indicated for MGUS, or indolent myeloma
Two randomized controlled trails have shown no benefit to early intervention