Essay 15- Multiple myeloma
Definition
- Multiple myeloma is a neoplastic disease characterized by plasma cell accumulation in the bone marrow, the presence of monoclonal protein in the serum and/or urine and tissue damage!
Etiology
- Exact etiology unknown!
- Translocations and alterations in promotor genes (chromosome 14) are commonly found and likely play a role
- Other oncogenes may participate in plasma cell proliferation (NRAS, KRAS, BRAF)
Pathophysiology
- MM is essentially a stage in the spectrum of monoclonal gammopathy!
- Thought to arise from a pre-malignant, asymptomatic phase of clonal plasma cell growth called monoclonal gammopathy of undetermined significance (MGUS)
- Genetic alterations may cause an increased expression of promoter genes or resistance to apoptosis, both resulting in higher plasma cell proliferation and population
- Under the "second hit" hypothesis, progression could also be a consequence of additional cytogenetic lesions gained by the original plasma cell clone
Durie and Salmon staging
- Durie and Salmon staging
- Class I- small tumour mass
- Class 2- intermediate tumour mass
- Class 3- increase in tumour mass
- A- creatinine is less than 2mg/dL
- B- creatinine is more than 2mg/dL
Symptoms
- Acronym for tissue damage:
- C- hypercalcemia
- R- renal impairment
- A- anemia
- B- bone disease
- Bone pain- resulting from vertebral collapse and pathological fractures
- Features of anemia (lethargy, weakness)
- Recurrent infections
- Features of renal failure and/or hypercalcemia
- Abnormal tendency to bleed- platelet function may be disrupted
- Amyloidosis- seen in 5%
- Hyperviscosity syndrome- seen in 2%
Diagnosis
- Symptomatic myeloma is diagnosed if there is:
- Monoclonal protein in serum and/or urine
- Increased clonal plasma cells in the bone marrow
- Related organ or tissue impairment
- Lab findings:
- CBC- normochromic, normocytic or macrocytic anemia
- Presence of paraproteinemia- IgG in 60% of cases and IgA in 20%
- Elevated serum Ig free light chains
- Immunoparesis- reduced normal serum IgG, IgA, IgM
- High ESR
- Hypercalcemia
- Bone marrow- increased plasma cells
- Greater than or equal to 10%!
- Radiography- osteolytic areas without evidence of surrounding osteoblastic reaction
- Raised serum creatinine in 20%
Treatment
Supportive
- Renal impairment- hydration with 3L of water a day
- Dialysis if indicated
- Bone disease and hypercalcemia- bisphosphonates (zoledronic acid) and rehydration using isotonic saline, diuretic and corticosteroid
- Compression paraplegia- surgical decompression laminectomy or irradiation
- Anemia- transfusion or EPN
- Bleeding- plasmapheresis
- Infections- oral antibiotics (broad) or antifungal agents)
Specific
Intensive combination chemo
- 4-6 courses of chemo
- Followed by autologous SCT (high procedure-related mortality)
- Drugs used combine 2 or 3 which are bortezomib, dexamethasone, thalidomide, lenalidomide, cyclophosphamide!
- VTD – bortezomib (velcade), thalidomide and dexamethasone