Treatment For Multiple Myeloma
- Responsive disease before transplant.
- Application of transplantation afterfirst-line therapy.
Myeloablative ASCT has significant toxic effects , but the possibility of a potent andpossibly curative graft-versus-myeloma effect in a minority of patients may offset the high transplant-related mortality. In one anecdotal series of 60 patients who underwent ASCT, six of the patients relapsed between 6 and 12 years, suggesting that late relapses still occur with this type of consolidation.
The lower transplant-related mortality from nonmyeloablative approaches has been accompanied by a greater risk of relapse. Since the introduction of lenalidomide and bortezomib, a trial exploring donor versus no donor comparison of ASCT versus autologous SCT and nonmyeloablative allogeneic SCT in 260 untreated patients showed no difference in PFS or OS. This result contrasted with two older trials , which suggested improvement of PFS and OS with a sibling donor. Given the lack of evidence so far that the high-risk patients benefit from allogeneic SCT in this era of novel new agents, it remains debatable whether ASCT should be offered in the first-line setting outside the context of a clinical trial.
Salvage autologous bone marrow or peripheral stem cell transplantation after relapse from first transplantation
What Is An M
Q. Heres a question from Twitter: Can you explain to me what the M protein in multiple myeloma is?
A. Multiple myeloma is a malignant, clonal disorder of plasma cells that originates in the bone marrow. Its a relatively common disorder, accounting for 1% of all malignancies and 10% of all hematologic malignancies in adults. Patients present with painful, lytic lesions of the bones, recurrent and persistent infections, weakness, renal failure, and hypercalcemia. The prognosis is generally not great, but new chemotherapeutic agents seem to hold some promise.
Patients with myeloma have a monoclonal proliferation of plasma cells in the bone marrow, meaning that there are a ton of malignant plasma cells that all originated from the same initial cell. In the bone marrow aspirate above, you can see tons of malignant plasma cells. A few look a lot like plasma cells, with clock-face chromatin and a hof and everything, but others look for all the world like blasts. Thats one thing to remember about myeloma malignant plasma cells dont always resemble their nice little benign counterparts.
In myeloma, the immunoglobulin is monoclonal, so it all migrates to exactly the same spot on the gel! Which gives you a big spike or a very distinct, crisp, strong band . This spike is called an M-spike , and the corresponding monoclonal protein that it represents is called an M protein.
A few other things to note about this M protein:
Magnetic Resonance Imaging Scans
Like CT scans, MRI scans show detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. A contrast material called gadolinium may be injected into a vein before the scan to see details better.
MRI scans are very helpful in looking at bones, the brain, and the spinal cord. Because MRI can find plasmacytomas that cant be seen on regular x-rays, they can be helpful if the patient has pain in a bone but nothing abnormal is seen on the x-ray. MRI can also be used to look at the bone marrow in patients with multiple myeloma.
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Monoclonal Gammopathy And Primary Care
ABSTRACT: With an aging population in Canada, a rise in malignant plasmaproliferative disease can be expected. In the majority of cases, this is preceded by monoclonal gammopathy. However, not all cases of monoclonal gammopathy progress to malignant disease over time. Primary care providers can benefit from considering common concerns related to management and follow-up of monoclonal gammopathy of undetermined significance : When is MGUS likely to be encountered in general practice? What investigations should be undertaken? How should MGUS be managed? What indicates a risk of progression from MGUS to malignant disease? In established MGUS, what follow-up investigations should be undertaken? When should the possibility of systemic AL amyloidosis be investigated? Answers to these questions based on consensus guidelines and recommendations can help primary care providers play a significant role in managing patients with monoclonal gammopathy of undetermined significance, especially those patients found to be at low risk for progression.
Even though most patients diagnosed with monoclonal gammopathy of undetermined significance will never develop malignant disease, follow-up is needed to identify those patients at risk of progression.
Serum protein electrophoresis and immuno-electrophoresis strips kindly supplied by Allison Venner, PhD.
Lab Tests To Confirm A Diagnosis
After your doctor takes samples of your blood and bone marrow, a hematopathologist confirms a diagnosis, identifies the myeloma stage and looks for certain changes in your chromosomes. A hematopathologist is a specialist who studies blood cell diseases by looking at samples of blood and marrow cells and other tissues. The test results determine the direction your treatment will take.
The hematopathologist performs a cytogenetic analysis to identify certain changes in chromosomes and genes. This can involve one or both of the following tests:
- G-banding karyotyping examines your chromosomes’ arrangement, size, shape and number using a special dye called Giemsa to get a better look at the banding patterns of chromosome pairs.
- Fluorescence in situ hybridization is an extra-sensitive test that detects chromosome changes in cells.
Common cytogenetic abnormalities that affect myeloma cells include:
- Deletion of chromosome 13. Deletion of chromosome 13 is associated with myeloma that responds poorly to chemotherapy. Newer drugs, however, are helping to improve response.
- Translocation of chromosome 14. Chromosome 14 commonly involves translocations between it and chromosomes 4, 11 or 16.
- An abnormality or loss of the short arm of chromosome 17. An important tumour suppressor, a gene called p53, is found in chromosome 17. Damage to 17 can indicate how quickly the disease is progressing.
In addition, doctors stage myeloma to help them decide on the best treatment plan.
Serum Heavy/light Chain Assay Or Hevylite Test
The Hevylite® assay is a blood test that measures the intact immunoglobulins. It measures:
- the intact heavy and light chain protein made by the myeloma cells
- the heavy- and light-chain-bound immunoglobulin protein made by normal plasma cells
If your myeloma protein is, for example, IgA kappa, the intact immunoglobulin that is its normal counterpart will be IgA lambda.
Serum Free Light Chain Assay Or Freelite Testing
The serum free light chain assay is used for diagnosis and monitoring of myeloma. Immunoglobulin proteins are made up of two kinds of molecules, heavy chains and light chains .
These heavy and light chains are usually bound together as intact immunoglobulins. For reasons we do not know, the plasma cells produce more light chains than heavy chains. The excess, or unbound, light chains circulate freely in the blood. Hence, they are called free light chains. These free light chains are present in both healthy individuals and in patients with myeloma and related disorders. Related disorders include:
- light chain deposition disease
- Waldenströms macroglobulinemia
Patients with myeloma may learn that their cells secrete:
- both heavy and light chains
- only heavy chains
- only light chains
Some patients, when assessed by SPEP, appear to secrete no M-protein at all. These patients’ myeloma cells secrete no heavy chain protein, only a very small amount of light chain protein. The Freelite test is used for patients who
- only secrete light chains, which is often called Bence-Jones myeloma.” .
- secrete both heavy and light chains
- secrete very low levels of protein, also known as oligosecretory myeloma
The Freelite assay is also used to:
- diagnose and monitor patients with MGUS, a non-cancerous elevation in monoclonal protein. The Freelite assay can help to assess if a patient’s MGUS may develop into active myeloma.
- monitor patients with smoldering or asymptomatic myeloma .
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Serum And Urine Protein Electrophoresis
Serum protein electrophoresis is a test that measures the amount of heavy chain monoclonal protein made by myeloma cells. Learn more at Types of Myeloma.
SPEP separates all the proteins in the blood according to their electrical charge. Urine protein electrophoresis, or UPEP, does the same thing for proteins in the urine.
The first graph represents a normal SPEP result. It shows:
- a peak in the measurement of albumin
- lower levels of the other proteins, grouped into areas labeled alpha 1 and 2
- gamma, which is where the antibody proteins lie on the graph
The second graph represents the result for a patient with myeloma. In addition to the spike for albumin, there is another tall spike. The red arrow in the gamma region of the graph indicates this spike.
A pathologist measures the area under the spike, or curve, and subtracts the normal level of gamma globulins from the total. The result is your level of monoclonal protein .
SPEP and UPEP tell us how MUCH monoclonal protein there is, but not the type. Monoclonal protein is the output of myeloma cells in most people with myeloma. Yet, every persons myeloma is unique. The output of monoclonal protein can vary from patient to patient. It can also can vary in how that amount relates to the behavior of the myeloma.
SPEP and UPEP don’t measure myeloma cells they measure the output of myeloma cells. Peoples myeloma cells dont reproduce at the same rate or secrete the same amount of protein per cell.
Treatment Options For Mgus
Multiple myeloma, other plasma cell dyscrasia,or lymphoma will develop in 12% of patients by 10 years, 25% of patients by 20 years, and 30%of patients by 25 years.
Allpatients with MGUS are generally kept under observation to detect increases inM protein levels and development of a plasma cell dyscrasia. Higher levels of initial M protein levels may correlate with increased risk of progression to multiple myeloma. In a large retrospective report, the risk of progression at 20 years was 14% for an initial monoclonal protein level of 0.5 g/dL or less, 25% for a level of 1.5 g/dL, 41% for a level of 2.0 g/dL, 49% for a level of 2.5 g/dL, and 64% for a level of 3.0 g/dL.
Treatmentis delayed until the disease progresses to the stage that symptoms or signsappear.
Patients with MGUS or smoldering myeloma do not respond morefrequently, achieve longer remissions, or have improved survival if chemotherapy isstarted early while they are still asymptomatic as opposed to waiting forprogression before treatment is initiated. Newer therapies have not been proven to prevent or delay the progression of MGUS to a plasma cell dyscrasia.
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How Is The Test Used
Protein electrophoresis is used to identify and measure the presence of abnormal proteins, the absence of normal proteins, and/or to detect various protein electrophoresis patterns associated with certain conditions, as found in blood, urine or other body fluids.
The information from protein electrophoresis can provide clues that a disease or condition is affecting protein production or loss of protein, but the results usually do not provide a definitive diagnosis. Instead, additional follow-up tests are needed to investigate the cause and to try to identify the nature of the underlying disease.
Serum electrophoresis may be used to:
Monoclonal Band In Gamma Region
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Serum Free Light Chains
This blood test can measure the light chain levels in the blood and is done when looking for myeloma or light chain amyloidosis.
This is most helpful in the rare cases of myeloma in which no M protein is found by SPEP. Since the SPEP measures the levels of intact antibodies, it cannot measure the amount of light chains only.
This test also calculates thelight chain ratio which is used to see if there is one type of light chain more than the other. There are 2 kinds of light chains: kappa and lambda. Normally, they are present in equal amounts in the blood, giving a ratio of 1 to 1. If there is more of one type of light chain than the other, the ratio will be different, which can be a sign of myeloma.
Treatment Options For Extramedullary Plasmacytoma
Treatment options for extramedullary plasmacytoma include the following:
Patients with isolated plasma cell tumors of soft tissues, most commonlyoccurring in the tonsils, nasopharynx, or paranasal sinuses, may need to haveskeletal x-rays and bone marrow biopsy andevaluation for M protein in serum and urine.
About 25% of patients have serum and/or urine M protein this frequently disappears after adequate radiation.
Extramedullary plasmacytoma is a highly curable disease with progression-free survival ranging from 70% to 87% at 10 to 14 years after treatment with radiation therapy .
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Immunofixation Electrophoresis Of Blood Or Urine
Immunofixation electrophoresis of blood or urine is the counterpart to SPEP and UPEP. IFE tells us the TYPE of monoclonal protein in the blood and/or urine but not the amount. IFE testing separates proteins by electrical charge. IFE measures only the monoclonal or abnormal proteins, not the normal ones
The result is either negative or positive for the presence of a particular type of monoclonal protein.
*Note: Darzalex can influence the results of IFE if a patient has IgG Kappa myeloma and is being evaluated for complete response. The patient may be in a very deep complete response, but a tiny band of IgG Kappa will show up on the test.
What Three Tests Are Used To Diagnose 1
Serum protein electrophoresis . When blood proteins are separated on the basis on electrical migration in gel, several bands are formed. One of these, the 1 band, consists mostly of 1-antitrypsin. Therefore, an 1-antitrypsin deficiency results in a flattening of the 1 band on SPEP.
Direct assay that uses a monoclonal antibody against 1-antitrypsin. The degree of binding can be measured in a spectrophotometer by rate nephelometry.
1-Antitrypsin phenotype. Only a few labs in the United States run this test, which designates the allelic protein types in the serum . Patients with protein of the ZZ type are said to be homozygotic for Z-type 1-antitrypsin deficiency. This is the form most frequently associated with significant liver disease. If Z protein is trapped in hepatocytes, it can be seen in liver tissue as small globules that stain with the periodic acidSchiff reaction and resist subsequent digestion with an enzyme called diastase. An immunostain is also available in some institutions.
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A Monoclonal Immunoglobulin Is Present Now What
Q. I have multiple myeloma, and I read your post What is an M-spike, and it was excellent contribution which I have been looking for in months. Please, can you tell me how the M-spike is quantifed?
A. Thats a great question! As you alluded to, there are a couple ways of looking at a monoclonal antibody: identification and quantification . Both pieces of information are useful in diagnosing and following multiple myeloma.
Is a monoclonal protein present?The first thing thats usually done in the lab is serum protein electophoresis . This procedure tells you whether there is a monoclonal protein present. You also do this procedure using urine, because sometimes myeloma cells will only make light chains, which end up being peed out in the urine . In an SPEP, the proteins in the serum are separated by regular old electrophoresis, using a gel. The gel is stained with a dye, and the percent of protein in the various fractions is is determined.
You can see an example above, with normal serum proteins in green, and proteins from a patient with myeloma in red. Albumin, as you can see, is the most abundant protein in blood, and it has its own region way on the left. Immunoglobulins usually migrate to the gamma region you can see a small, broad bump in the normal serum and a big spike in the blood from the patient with myeloma .
How much of it is present?To quantify immunoglobulins, you can do one of two things:
Is There Anything Else I Should Know
Immunizations within the previous six months can increase antibodies , as can drugs such as phenytoin , procainamide, oral contraceptives, methadone, and intravenous immunoglobulin and anti-cancer immunotherapy.
Aspirin, bicarbonates, chlorpromazine , corticosteroids, and neomycin can affect protein electrophoresis results.
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Ask A Laboratory Scientist
This form enables patients to ask specific questions about lab tests. Your questions will be answered by a laboratory scientist as part of a voluntary service provided by one of our partners, American Society for Clinical Laboratory Science. Please allow 2-3 business days for an email response from one of the volunteers on the Consumer Information Response Team.
If I Have An Abnormal Monoclonal Immunoglobulin In My Blood Does It Mean That I Have Multiple Myeloma Or Some Other Type Of Cancer
Not necessarily. Monoclonal protein production may be due to a condition known as monoclonal gammopathy of undetermined significance . Most people with MGUS initially have a benign course but may progress to a more serious condition. They must continue to be monitored regularly with a serum protein electrophoresis test, or sometimes a free light chain test, depending on which monoclonal protein is being produced. MGUS is present in about 4% of Caucasians over the age of 50 and progresses at a rate of 1% per year to multiple myeloma.
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