Justin A. Crocker. 1 of the monoclonal gammopathies Neoplastic proliferation of immunoglobulin...

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 10- 30 % * 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-2 <3.5 (mg/L) and the albumin

is > 3.5 (g/dL). Stage II: Neither stage I or III, meaning that

either: beta-2 is between 3.5-5.5 (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