Chapter 106. Plasma Cell Disorders (Part 6)

The clinical evaluation of patients with myeloma includes a careful physical examination searching for tender bones and masses. Only a small minority of patients has an enlargement of the spleen and lymph nodes, the physiologic sites of antibody production. Chest and bone radiographs may reveal lytic lesions or diffuse osteopenia. MRI offers a sensitive means to document extent of bone marrow infiltration and cord or root compression in patients with pain syndromes. A complete blood count with differential may reveal anemia. Erythrocyte sedimentation rate is elevated. Rare patients (~2%) may have plasma cell leukemia with 2000 plasma cells/µL. This...
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Chapter 106. Plasma Cell Disorders (Part 6) Chapter 106. Plasma Cell Disorders (Part 6) The clinical evaluation of patients with myeloma includes a carefulphysical examination searching for tender bones and masses. Only a smallminority of patients has an enlargement of the spleen and lymph nodes, thephysiologic sites of antibody production. Chest and bone radiographs may reveallytic lesions or diffuse osteopenia. MRI offers a sensitive means to documentextent of bone marrow infiltration and cord or root compression in patients withpain syndromes. A complete blood count with differential may reveal anemia.Erythrocyte sedimentation rate is elevated. Rare patients (~2%) may have plasmacell leukemia with >2000 plasma cells/µL. This may be seen in disproportionatefrequency in IgD (12%) and IgE (25%) myelomas. Serum calcium, urea nitrogen,creatinine, and uric acid levels may be elevated. Protein electrophoresis andmeasurement of serum immunoglobulins and free light chains are useful fordetecting and characterizing M spikes, supplemented by immunoelectrophoresis,which is especially sensitive for identifying low concentrations of M componentsnot detectable by protein electrophoresis. A 24-h urine specimen is necessary toquantitate protein excretion, and a concentrated aliquot is used for electrophoresisand immunologic typing of any M component. Serum alkaline phosphatase isusually normal even with extensive bone involvement because of the absence ofosteoblastic activity. It is also important to quantitate serum β2-microglobulin (seebelow). Serum soluble IL-6 receptor levels and C-reactive protein may reflectphysiologic IL-6 levels in the patient. The serum M component will be IgG in 53% of patients, IgA in 25%, andIgD in 1%; 20% of patients will have only light chains in serum and urine.Dipsticks for detecting proteinuria are not reliable at identifying light chains, andthe heat test for detecting Bence Jones protein is falsely negative in ~50% ofpatients with light chain myeloma. Fewer than 1% of patients have no identifiableM component; these patients usually have light chain myeloma in which renalcatabolism has made the light chains undetectable in the urine. IgD myeloma mayalso present as light chain myeloma. About two-thirds of patients with serum Mcomponents also have urinary light chains. The light chain isotype may have animpact on survival. Patients secreting lambda light chains have a significantlyshorter overall survival than those secreting kappa light chains. It is not clearwhether this is due to some genetically important determinant of cell proliferationor because lambda light chains are more likely to cause renal damage and formamyloid than are kappa light chains. The heavy chain isotype may have an impacton patient management as well. About half of patients with IgM paraproteinsdevelop hyperviscosity compared with only 2–4% of patients with IgA and IgG Mcomponents. Among IgG myelomas, it is the IgG3 subclass that has the highesttendency to form both concentration- and temperature-dependent aggregates,leading to hyperviscosity and cold agglutination at lower serum concentrations. The various staging systems for patients with myeloma (Table 106-3) arefunctional systems for predicting survival and are based on a variety of clinicaland laboratory tests, unlike the anatomic staging systems for solid tumors. TheDurie-Salmon staging system is based on the hemoglobin, calcium, M component,and degree of skeletal involvement; the total-body tumor burden is estimated to below (stage I), intermediate (stage II), or high (stage III), and the stages are furthersubdivided on the basis of renal function [A if serum creatinine 2)]. Patients in stage IA have a median survival of >5 yearsand those in stage IIIB about 15 months. This staging system has been found notto predict prognosis after treatment with high-dose therapy or the novel targetedtherapies that have emerged. Table 106-3 Myeloma Staging Systems Durie-Salmon Staging SystemStage Criteria Estimated Tumor Burden, x 1012 cells/m2I All of the following: 1. Hemoglobin 100 g/L (>10 g/dL) 2. Serum calcium g/L ( a. IgG level >70 g/L (>7 g/dL) b. IgA level >50 g/L (>5 g/dL) c. Urine light chains >12 g/24 h Level Stage Median Survival, Months Subclassification based on serum creatin ...