Multiple myeloma

 clonal malignancy of the differentiated β lymphocyte—the plasma cell.

• occurs predominantly in the geriatric population
• It is regarded as a disease of the elderly
  • median age at diagnosis of about 70 years
• classic presenting triad in an older person is
  • anaemia
  • back pain
  • elevated ESR
• slightly more commonly seen in males than females (1.4:1)
• thought to arise from a pre-malignant asymptomatic phase:
  • clonal plasma cell growth called monoclonal gammopathy of undetermined significance (MGUS)
    • detecting monoclonal immunoglobulins in the blood or urine without evidence of end-organ damage.
    • quite common and is known to be detectable in over 3% of persons above age 50
    • exact causes of MGUS development and progression to MM remain unknown.

Clinical

• disease of elderly (median age of px = 60)
• complex illness with interrelationships b/w
  • to the activation of osteoclasts and suppression of osteoblasts 🡪 bone destruction 🡪
    • #’s of long bones
    • vertebral collapse (can 🡪 SC compression)
    • hyperCa2+
  • bone marrow infiltration 🡪
    • anaemia
    • neutroaenia
    • thrombocytopaenia
    • together with the paraprotein production 🡪 symptoms of hyperviscocity ( venous thromboembolism and hyperviscosity syndrome)
  • renal impairment owing to
    • excess monoclonal immunoglobulins 🡪 deposition of light chains
    • hyperviscosity
    • hyperCa2+
    • hyperuricaemia
    • deposits of amyloid (rare)

Life threatening Cx’s of myeloma

• Renal impairment (often a consequence of hyperCa2+ 🡪 may need peritoneal/haemodialysis)
• HperCa2+ 🡪 anorexia, fatigue, constipation, polydipsia, polyuria, confusion, or stupor 🡪 treat with rehydration and bisphosphonates such as pamidronate
• Spinal cord compression 🡪 treat with dexamethasone followed by RT to lesion delineated by MRI
• hyperviscosity due to high circulating levels of paraprotein 🡪 risk for thrombosis,oronasal bleeding, blurred vision, retinal hemorrhage, seizure, other neurologic symptoms, confusion, dyspnea, and heart failure 🡪 correct by plasmapheresis
• ↓↓ in N immunoglobulin levels 🡪 can 🡪 reccurrent infection (most common infections are pneumonia and urinary tract infections, mostly with organisms such as Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli. )

Diagnostic criteria comprise the presence of:

• paraprotein in serum (on electrophoresis)
• Bence–Jones protein in urine
• bony lytic lesions on skeletal survey

• anaemia and renal failure at Px 🡪 very poor prognosis (50% die in 9 months)
• serum B2 microglobulin level 🡪 prognostic factor
• clinical stage of disease at Px 🡪 prognostic factor

Staging according to Durie Salmon criteria

• based on the tumor cell mass, hemoglobin, calcium, IgA and IgG levels, urine monoclonal protein levels, and the extent of bone damage on X-rays
  • 1 = earliest 
  • III = most advanced

Median survival for patients with myeloma = 3-4 years. (younger patients may live longer)

Symptoms

• symptoms of anaemia (73%)
• bone pain (58%) (most commonly backache owing to vertebral involvement
• symptoms of renal failure – elevated creatinine (48%)
• fatigue (32%)
• symptoms of hyper Ca – hypercalcemia (28%)
• weight loss (24%)
• recurrent infection
• rarely symptoms of hyperviscosity and bleeding from thrombocytopaenia

Investigations

• FBC (Hb N or LOW, WCC N or LOW, platelets N or low)
• ESR (almost always HIGH)
• Blood film (maybe rouleax formation as a conseuqnce of paraprotein)
• U & E (may be evidence of renal failure)
• Serum Ca2+ (N or HIGH)
• Serum ALK PHOS (usually N)
• Total protine (N or HIGH)
• Serum albumin (N or LOW)
• Serum protein electrophoresis (shows monoclonal band)
• Uric acid (N or HIGH)
• Skeletal survey (may show characteristic lytic lesions best seen in skull)
• 24 hour urine – for assessment of light chain excretion
• BMA (shows characteristic infiltration by plasma cells)

Treatment

• correct anaemia and infection
• bone pain helped most quickly by RT
• Pathological #’s may be prevented by prompt surgery (pinning of lytic bone lesions)
• Use of alkylating agents (melphalan or cyclophosphamide) in conjuction with prednisolone