Healthy Older Man With Abnormal IgG Level

The results of a preoperative serum protein electrophoresis (SPEP) test wereabnormal in a 72-year-old man who underwent a successful hernia repair2 weeks earlier.

HISTORYThe patient is healthy and has no chronic medical problems. He takesibuprofen and acetaminophen as needed for hip pain, which is worse on the leftside. He has no bone pain elsewhere and denies weakness, fatigue, and bleedingsymptoms, such as bruising. Review of systems is noncontributory.

PHYSICAL EXAMINATION
Blood pressure is 132/80 mm Hg. Mucous membranes are not pale, andlymph nodes are not enlarged. Heart and lungs are normal. The herniorrhaphyscar on the right is healing well. No bony tenderness is evident in the ribs,spine, or pelvis on compression or percussion.

LABORATORY AND IMAGING RESULTSLaboratory results from the preoperative and postoperative evaluations includea white blood cell count of 8700/?L, with a normal differential; hemoglobinconcentration, 14.4 g/dL; and a normal platelet count. Serum chemistriesand serum albumin, calcium, creatinine, and alkaline phosphatase levels arenormal. The SPEP test shows a small monoclonal band, and immunoelectrophoresisreveals an IgG band that measures 1198 mg/dL; IgM and IgA levelsare normal. Urinalysis and urine protein electrophoresis results are normal.An MRI scan of the hips and pelvis reveals severe degenerative disease in bothhips, greater in the left than in the right, but no other bone pathology.

Which of the following is the most appropriate next step for thispatient?

A. Initiate therapy for multiple myeloma using melphalan and prednisone.
B. Order a bone marrow biopsy and aspiration for pathologic evaluationand flow cytometry analysis.
C. Refer the patient for evaluation for autologous marrow transplantationfor multiple myeloma.
D. Reassure the patient that in most cases these types of protein abnormalitiesresolve with time.
E. Arrange to follow the patient at 6- or 12-month intervals to monitorSPEP levels.

CORRECT ANSWER: E
This case highlights the problems involved in the managementof monoclonal gammopathy of unknown significance(MGUS). The incidence of MGUS is relatively high-andprobably increasing-because of both the greater numberof SPEP tests being performed and the enhanced sensitivityof newer testing methods. Studies reveal a 2% incidence inpersons older than 50 years, a 3% incidence in those olderthan 70 years, and a 5% to 10% incidence in those older than80 years.¹

The principal question in patients with MGUS iswhether the gammopathy is part of a more ominous plasmacell dyscrasia, such as multiple myeloma. The first stepin the evaluation of these patients is to determine whetherother criteria for myeloma are present. This involves testingthe urine for monoclonal protein (M-protein) (thereshould be noneor, at the most,moderateamounts ofmonoclonal lightchains), checkingthe hemogramand calcium andcreatinine levelsand, in patientsin whom the Mproteinlevel isgreater than2 g/dL, obtainingskeletal radiographsto detectosteolytic disease.Abnormalresults on any ofthese tests are strong diagnostic and prognostic clues formyeloma.^2,3

Traditionally, a marrow examination has also beenperformed to ensure that plasma cells are morphologicallynormal and comprise less than 10% of the marrow cellcount. Kyle and associates¹ recently reported that thiscumbersome test can be deferred if the gammopathy isless than 2 g/dL, as it is in this man. In addition, the patienthas no other abnormalities that suggest frank multiplemyeloma. Thus, a marrow study (choice B) can safelybe deferred.

Choice C, evaluation for a bone marrow transplantation,and choice A, chemotherapy, represent even moreaggressive stances and are thus not appropriate. Althoughnewer data suggest a definite role for bone marrow transplantationin myeloma, the cutoff age for autologous transplantationthat is used by most authorities is 65 years.

Therefore, even if myeloma had been diagnosed, suchtherapy might not be appropriate for this patient.^4,5

Choice E (regular monitoring with SPEP) reflectsthe excellent new data on the natural history of MGUS.¹In a longitudinal, 35-year follow-up study of more than1000 patients, the risk of developing myeloma or otherserious plasma cell disease (eg, amyloidosis or Waldenstrmmacroglobulinemia) was found to be low as longas the M-protein level was less than 3 g/dL. The overallincidence of progression from MGUS to myeloma wasabout 1% per year. However, MGUS spontaneously resolvedwith time in only 0.4% of patients; thus, choice D(reassurance alone) is incorrect.

The risk of progression 10 years after MGUS wasdiagnosed was 6% for patients whose M-protein level wasless than 0.5 g/dL, 7% for those whose level was 1 g/dL,11% for those whose level was 1.5 g/dL, 20% for thosewhose level was 2 g/dL, and 34% for those whose levelwas greater than 3 g/dL.1 This patient's level is 1.2 g/dL;therefore, he has approximately a 10% risk of a plasma cellneoplasm developing in the next 10 years. He can be safelyand conservatively monitored semiannually or annually.More invasive testing can be done if his gammopathyreaches a more worrisome level.

References:

REFERENCES:1. Kyle RA, Therneau TM, Rajkumar SV, et al. A long-term study of prognosis inmonoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346:564-569.
2. Baldini L, Guffanti A, Cesana BM, et al. Role of different hematologic variablesin defining the risk of malignant transformation in monoclonal gammopathy.Blood. 1996;87:912-918.
3. Bataille R, Harousseau JL. Medical progress: multiple myeloma. N Engl JMed. 1997;336:1657-1664.
4. Attal M, Harousseau JL, Stoppa AM, et al, for the Intergroupe Français duMyelome. A prospective, randomized trial of autologous bone marrow transplantationand chemotherapy in multiple myeloma. N Engl J Med. 1996;335:91-97.
5. Siegel DS, Desikan KR, Mehta J, et al. Age is not a prognostic variable withautotransplants for multiple myeloma. Blood. 1999;93:51-54.