DOI: 10.18410/jebmh/2015/852
ORIGINAL ARTICLE
BIOCHEMICAL PROFILE AND ELECTROPHORETIC PATTERN IN
MULTIPLE MYELOMA PATIENTS
Nihar Ranjan Dash1, Biswajit Mohanty2
HOW TO CITE THIS ARTICLE:
Nihar Ranjan Dash, Biswajit Mohanty. “Biochemical Profile and Electrophoretic Pattern in Multiple Myeloma
Patients”. Journal of Evidence based Medicine and Healthcare; Volume 2, Issue 39, September 28, 2015;
Page: 6166-6170, DOI: 10.18410/jebmh/2015/852
ABSTRACT: OBJECTIVE: To study different biochemical parameters and serum agarose gel
electrophoresis patterns of patients consistent with clinical symptoms of multiple myeloma.
SETTING: The study was carried out at Apollo Hospitals, Bhubaneswar, the premier tertiary care
Centre in Orissa. MATERIALS AND METHODS: A total of 1057 referred cases for protein
electrophoresis were analysed and reviewed between March 2010 to July 2015. RESULTS: Out
of 1057 cases of protein electrophoresis 94 were confirmed cases of Multiple Myeloma. The mean
age of detected cases of Multiple Myeloma was 64.8 years. There was a male prevalence.
Anaemia was initially found in 85.0% cases. The mean protein concentration was 9.0gm/dL and
albumin was 3.2gm/dL. Hypercalcemia was seen in 28.0% case. Serum Creatinine level of
>2.0mg/dL was seen in cases 38.0% case. Serum protein electrophoresis revealed a localized
band in 99% of patients. Immunofixation electrophoresis showed monoclonal band in 92 cases
(98%) and a biclonal pattern in 2 cases (2%). Light chain myeloma was detected in 11 cases
(19.0%). CONCLUSION: Serum protein electrophoresis should be routinely used in all elderly
patients with features of bone pain, anemia and hyperproteinemia. It is still the gold standard for
diagnosing Multiple Myeloma and it collaborate well with the clinical, biochemical and radiological
findings. The abnormal band can be well characterized by Immunofixation electrophoresis.
KEYWORDS: Multiple Myeloma; Protein electrophoresis; Immunofixation.
INTRODUCTION: Multiple myeloma is a malignant disorder characterized by proliferation of
single clone of plasma cells derived from B-cells in the bone marrow. It is the second most
common adult hematological malignancy, and it is the most common cancer with skeleton as its
primary site.1
The median age at diagnosis of multiple myeloma is 70 years, and the occurrence
increases with age.2 Fatigue, bone pain, lytic bone disease, renal insufficiency, anemia and
hypercalcemia are commonly encountered in multiple myeloma patients. Protein electrophoresis
should be undertaken whenever multiple myeloma, is suspected. Serum protein electrophoresis
(SPE) is the mainstay laboratory test for the detection of abnormal monoclonal proteins. Mprotein is generally observed as a localized band which is frequently seen on gamma or beta
region, it may also be seen on alpha-2-globulin region in rare situations.3,4 Very rarely biclonal
gammopathy can be seen.5 The nature of the monoclonal protein is then characterized and
confirmed by an immunofixation electrophoresis (IFE).
The purpose of the prospective study was to assess the biochemical profile and
electrophoretic pattern of all Multiple Myeloma patients that were detected at our hospital during
the period from March 2010 to July 2015.
J of Evidence Based Med & Hlthcare, pISSN- 2349-2562, eISSN- 2349-2570/ Vol. 2/Issue 39/Sept. 28, 2015 Page 6166
DOI: 10.18410/jebmh/2015/852
ORIGINAL ARTICLE
MATERIALS AND METHODS: All patients referred to the Department for protein
electrophoresis during the period from March 2010 to July 2015 were analysed and the
biochemical and electrophoretic pattern of all diagnosed Multiple Myeloma patients was studied.
Out of 1057 cases 94 were confirmed cases of Multiple Myeloma. The diagnosis of multiple
myeloma was based on the following findings: (1) increased numbers of abnormal, atypical, or
immature plasma cells in the bone marrow or histologic proof of plasmacytoma; (2) presence of
an M-protein in the serum; or (3) bone lesions consistent with those of multiple myeloma.
All biochemical investigation was done on Beckman Coulter AU 480. Hematological indices
were measured on SYSMEX Cell Counter (XT-1800i). Serum Protein electrophoresis and
Immunofixation electrophoresis was done on Helena Biosystems using SAS-MX SP-10 SB and
SAX-MX IFE-1 kit respectively. The results were analysed using Helena software PT version 3.0.
The serum protein fractions analyzed included total protein, albumin, α1-globulin, α2globulin, β1-globulin, β2-globulin, and γ- globulin. Laboratory parameters evaluated included
hemoglobin, serum calcium, creatinine, β 2 Microglobulin and lactate dehydrogenase levels and
the erythrocyte sedimentation rate. The bone marrow studies were also included.
RESULTS: Table 1 shows the biochemical profile of 94 diagnosed case of Multiple Myeloma. The
mean Total protein in the diagnosed cases was 9.00±2.47gm/dL. Hyperproteinemia > 8.4gm/dL
was seen in 62% cases while hypoproteinemia <6.4gm/dL was seen in 2% case. In one case
hypogammaglobulinemia with M-spike in β2 globulin was marked. Anaemia was observed in 85%
cases. The mean serum Calcium was 9.77±0.28mg/dL. Renal involvement (Serum creatinine level
>2.0mg/dL) was seen in 38% cases. β2-Microglobulin was raised in all the cases with a mean
value of 8498±2312g/L. Figure 1 shows location of M-spike in all the cases. Majority of cases
(89%) the M-spike was found in γ-region followed by β- region (8% case). Biclonal pattern was
seen in 2 cases. Table 2 shows the type of M-protein in IFE. The most common type of heavy
chain produced in myeloma is IgG (67%) followed by IgA (12%). Free light chains were detected
in 19% cases. Figure 2 shows the percentage of plasma cells in bone marrow. In majority of
cases (92%) the plasma cell was >10%. In 30% cases it was more than 50%.
DISCUSSION: In our study the mean age of incidence was 64.8±8.9 years and there was a
male prevalence (65 out of 94 cases). 92% (85 cases) of cases were detected in the age group
50-79 years with the peak incidence in the age group 60-69 years (39%). Anemia (Hb<10.0
gm%) was initially present in 85.0% cases with mean hemoglobin level at 8.5±1.78 gm%. ESR
was seen to be elevated in all the cases and a value of >100mm/hr was observed in 82% cases.
Total protein and albumin levels were 9.0±2.47 and 3.2±0.56gm/dL respectively. Total protein to
albumin ratio was decreased in all patients. The mean serum Calcium was 9.77±0.28 mg/dL with
hypercalcemia (calcium>10.1mg/dL) in 28% cases. The mean serum creatinine level was
2.96±1.07mg/dL with level >2.0mg/dL in 38% cases. β2-Microglobulin had a mean value of
8498±2312 g/L.
Out of 1057 suspected case of Multiple Myeloma 94 (8.8%) were found to have
monoclonal gammopathy whereas Col. Chopra et al., found 24.4% samples to be positive for the
M protein by SPEP6 and Tripathy S. found 10.6% of samples to be positive.7 Out of 94 positive
J of Evidence Based Med & Hlthcare, pISSN- 2349-2562, eISSN- 2349-2570/ Vol. 2/Issue 39/Sept. 28, 2015 Page 6167
DOI: 10.18410/jebmh/2015/852
ORIGINAL ARTICLE
cases M-Spike was localized in gamma region in 89% cases, Beta region 8% cases and alpha
region in 1% cases. Biclonal gammopathy was noted in 2 cases (2%) while hypogammaglobulinemia was observed in 1 case. Col.G S Chopra et al reported that, 84.8% of the
cases had an M band in the gamma (γ) region and that 15.2% cases had an M spike in the beta
(β) globin region. Tripathy S reported M spike in the gamma region in 87.5% cases and 12.5%
cases in the beta region. Bone marrow aspirate showed Plasma cell >10% in 92% cases. The
mean bone marrow plasma cell was 31%. In normal individuals plasma cells constitute 1% in the
bone marrow but in Multiple Myeloma, tumor load in bone marrow increases up to 80 %
depending on severity.8,9
CONCLUSION: Multiple myeloma or plasma cell myeloma is a cancer that originates in plasma
cells. The myeloma cells grow in an out-of-control manner and accumulate in the bone marrow
throughout the body. Over time, the tumor cells may directly damage bones, causing fractures
and dangerously elevated blood calcium levels, and the overproduction of antibody may damage
the kidneys. Myeloma cells interfere with blood production, resulting in anemia or low red blood
cell counts. They also suppress normal antibody production, interfering with normal immunity and
leaving the patients vulnerable to infections. Elderly male complaining of bone pain and with
anemia should be further investigated. In some cases, individuals present with “smoldering” or
asymptomatic myeloma, and these patients are subject to “watchful waiting,” observation without
therapy while monitoring for the development of symptoms. Despite improvements in treatment
and longer survival, relapse is inevitable.
ACKNOWLEDGEMENT: IT Department at Apollo Hospitals, Bhubaneswar.
REFERENCES:
1. Babatunde O Oyajobi Multiple myeloma/hypercalcemia. Arthritis Research & Therapy 2007,
9(Suppl 1):S4 (doi: 10.1186/ar2168).
2. Nau KC and Lewis WD. Multiple myeloma: diagnosis and treatment. Am Fam Physician
2008; 78(7): 853-9.
3. Kyle AR, Rajkumar SV, Lust AJ. Monoclonal gammopathy of undetermined significance and
smoldering multiple myeloma. In: Greer JP, Foerster J, Lukens JN, Rodgers GM, Paraskevas
F, Glader B, editors. Wintrobe’s clinical hematology. Chapter 97. 11th ed. Philadelphia:
Lippincott Williams & Wilkins; 2004. p. 2566-7.
4. Longo DL, Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, et al.,
Plasma cell disorders. In Harrison’s principles of internal medicine. Vol. 1, Chapter 114. 14th
ed. New York: McGraw-Hill Co; 1998, p. 712-8.
5. Dash NR, Mohanty B. Multiple myeloma-a case of atypical presentation on protein
electrophoresis. Indian Journal of Clinical Biochemistry vol. 27 issue 1 March 2012. p. 100 –
102
6. Chopra GS, Gupta PK, Mishra DK. The evaluation of suspected monoclonal gammopathies:
the experience in a tertiary care hospital. MJAFI 2006; 62: 134-37.
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DOI: 10.18410/jebmh/2015/852
ORIGINAL ARTICLE
7. Tripathy S. The Role of Serum Protein Electrophoresis in the Detection of Multiple Myeloma.
Journal of Clinical and Diagnostic Research. 2012 November, Vol-6(9): 1458-1461.
8. Mehta KD, Khambu B, Lakhey M, Lakhey S, Baral N, Majhi S. Diagnosis of multiple myeloma
by demonstration of M protein in bone marrow aspirate by agar gel electrophoresis: a case
report. Kathmandu Univ Med J 2006; 4(4): 513-6.
9. Durie BG, Salmon S. A clinical staging system for multiple myeloma: Correlation of
measured myeloma cell mass with presenting clinical feautures, response to treatment and
survival. Cancer 1975; 36: 842-54.
PARAMETER
Total protein(gm/dL)
Albumin(gm/dL)
α1-Globulin(gm/dL)
α2-Globulin(gm/dL)
β-Globulin(gm/dL)
γ-Globulin(gm/dL)
Hemoglobin(gm%)
ESR(mm/hr)
Calcium(mg/dL)
Creatinine(mg/dL)
Lactate Dehydrogenase(U/L)
β2-Microglobulin(g/L)
MEAN±SD
9.00±2.47
3.20±0.56
0.4±0.1
0.88±0.4
1.0±0.5
1.74±0.9
8.5±1.78
109±32.6
9.77±0.28
2.96±1.07
235.5±187
8498±2312
Table 1: Biochemical Profile for 94 patients with Multiple Myeloma
Fig. 1: Location of M-Spike in serum
protein electrophoresis (n=94)
J of Evidence Based Med & Hlthcare, pISSN- 2349-2562, eISSN- 2349-2570/ Vol. 2/Issue 39/Sept. 28, 2015 Page 6169
DOI: 10.18410/jebmh/2015/852
ORIGINAL ARTICLE
Type of M-Protein
%
IgG κ
36
IgG λ
31
IgA κ
2
IgA λ
10
IgM κ
0
IgM λ
0
Free κ only
10
Free λ only
9
Biclonal IgA κ
1
Biclonal IgG λ
1
Table 2: Type of monoclonal component
evident on IFE (n=94)
Fig. 2: Plasma cell in bone marrow aspirate (n=94)
AUTHORS:
1. Nihar Ranjan Dash
2. Biswajit Mohanty
PARTICULARS OF CONTRIBUTORS:
1. Junior Consultant, Department of
Biochemistry & Therapeutic Drug, Apollo
Hospitals, Bhubaneswar.
2. Senior Consultant, Department of
Biochemistry & Therapeutic Drug, Apollo
Hospitals, Bhubaneswar.
NAME ADDRESS EMAIL ID OF THE
CORRESPONDING AUTHOR:
Dr. Biswajit Mohanty,
Plot No. 251,
Sainik School Road,
Unit 15, Bhubaneswar-751005.
E-mail: drbiswajit_m@apollohospitals.com
Date
Date
Date
Date
of
of
of
of
Submission: 09/09/2015.
Peer Review: 10/09/2015.
Acceptance: 14/09/2015.
Publishing: 23/09/2015.
J of Evidence Based Med & Hlthcare, pISSN- 2349-2562, eISSN- 2349-2570/ Vol. 2/Issue 39/Sept. 28, 2015 Page 6170