Justin A. Crocker

 1 of the monoclonal gammopathies  Neoplastic proliferation of immunoglobulin producing plasma cells (single clone), often resulting in extensive skeletal destruction with focal lytic lesions, bone pain, and hypercalcemia  Cause unknown  1% of all malignant disease and slightly more than 10% of hematologic malignancies in the US  Median age 66 (range 20 to 92)  Survival median is 3 years

Symptoms  Bone pain: back, chest, extremities  Weakness  Fatigue  Weight loss  Symptoms of hypercalcemia, renal insufficiency or amyloidosis

Signs  Pallor  Rare to have HSM or LAD  Extramedullary plasmacytoma: large, purplish, subcutaneous mass seen in the late course of the disease

Other Clinical Findings  Neurologic disease- radiculopathy, cord compression (plasmacytoma or vertebral body fracture), rare peripheral neuropathy  ID- strep pneumo, GN infections common  Lytic bone lesions- pathologic fracture, bone pain

Workup  CBC w/ diff  BMP including BUN/Cr and Ca  U/A  SPEP/UPEP  Bone survey (plain films) not bone scan  CT/MRI  b2 microglobulin, CRP and LDH,  Measurement of free monoclonal light chains if available  Bone marrow aspirate

Diagnostic criteria: International Myeloma Working Group  Calcium elevation  Renal insufficiency (Cr >1.7)  Anemia (<10)  Bone lesions (lytic lesions seen on CT or MRI)

Diagnostic criteria: International Myeloma Working Group cont.  M-protein in serum and/or urine  Bone marrow (clonal) plasma cells or plasmacytoma

WHO criteria  Major Criteria  BM plasmacytosis > 30%  Plasmacytoma on bx  Mspike in serum or urine: IgG > 3.5 g/dL or IgA > 2 g/dL or Urine Bence-Jones > 1g/24 hrs  1 major and 1 minor OR 3 minor criteria  Minor Criteria  * BM plasmacytosis of %  * Monoclonal protein  Lytic bone lesions  Reduced normal immunoglobulins to < 50% nml  * required if using “3 minor”

International Staging System  Based on the serum beta-2 microglobulin and serum albumin levels.  Stage I: beta (g/dL).  Stage II: Neither stage I or III, meaning that either: beta-2 is between (with any albumin level) OR the albumin is < 3.5 while the beta-2 is < 3.5  Stage III: Serum beta-2 is > 5.5

 Other hematologic malignancies (lymphoma/leukemia)  Solid masses  Sarcoid  Cirrhosis  Parasitic diseases  RA  Pyoderma gangrenosum  Sjogren’s syndrome  Cold agglutinin disease

Is it Symptomatic Multiple Myleoma?  20% of monoclonal gammopathies are secondary to another systemic illness  13.5% are due to plasma cell neoplasms (myeloma, solitary plasmacytoma, extramedullary plasmacytoma, osteosclerotic plasmacytoma  66% are MGUS

Other gammopathies Smoldering Mulitiple Myeloma  Serum monoclonal protien > 3 g/dL  Bone marrow plasma cells > 10%  No end organ damage related to plasma cell dyscrasia MGUS  Serum monoclonal protein < 3 g/dL  Bone marrow plasma cells < 10%  No end organ damage related to plasma cell dyscrasia

Other causes of osteolytic lesions  Renal cell cancer  Melanoma  Squamous cell cancers of the aerodigestive tract  Non-SC Lung CA  Thyroid CA  Non Hodgkins Lymphoma

Variations on Multiple Myeloma  Nonsecretory: 3% have no M- protein in serum or urine and remains nonsecretory in 76% in follow up- limits renal failure, no light chain excretion. No survival dif.  Light chain myeloma: 20% of MM is only light chain, no immunoglobulin heavy chain. Increased incidence of renal failure, ? Survival differences.

Therapies  High dose steroids  Chemo: Melphalan, alkylating agent Thalidomide  Stem cell transplant  No cure

Preventing complications  Treat hypercalcemia with IVF, natriuresis, steroids. Also can use calcitonin and/or IV zoledronic acid (bisphosphonate)  Radiation therapy to lytic lesions  Vaccinate for infection prevention  Renal failure- avoid contrast, maintain hydration  Erythropoietin for anemia improvement