multiple myeloma & mri

Multiple myeloma (MM) is an incurable clonal B-cell malignancy with terminally differentiated plasma cells. It afflicts approximately 55,000 people in the United States. Over the past 5 years, significant progress has been made in the diagnosis and assessment of patients with MM.  For the first time in decades, major therapeutic advances have been implemented in the treatment of MM patients. These include 2 new classes of agent: immunomodulatory drugs and proteosome inhibitors. In addition, clinical trials have solidified the role of hematopoietic stem cell transplant and established the benefits of post-transplant maintenance therapy. Finally, a number of new agents are in development that specifically target the myeloma cells and/or the bone marrow microenvironment. These advances have resulted in expanded treatment options, prolonged disease control and survival, and improved quality of life for patients with MM.

Because many organs can be affected by myeloma, the symptoms and signs vary greatly. A mnemonic sometimes used to remember the common tetrad of multiple myeloma is CRAB – C = Calcium (elevated), R = Renal failure, A = Anemia, B = Bone lesions.[

The presence of unexplained anemia, kidney dysfunction, a high erythrocyte sedimentation rate (ESR) and a high serum protein (especially raised immunoglobulin) may prompt further testing. A doctor will request protein electrophoresis of the blood and urine, which might show the presence of a paraprotein (monoclonal protein, or M protein) band, with or without reduction of the other (normal) immunoglobulins (known as immune paresis). One type of paraprotein is the Bence Jones protein which is a urinary paraprotein composed of free light chains (see below). Quantitative measurements of the paraprotein are necessary to establish a diagnosis and to monitor the disease. The paraprotein is an abnormal immunoglobulin produced by the tumor clone. Very rarely, the myeloma is nonsecretory (not producing immunoglobulins).

In theory, multiple myeloma can produce all classes of immunoglobulin, but IgG paraproteins are most common, followed by IgA and IgM. IgD and IgE myeloma are very rare. In addition, light and or heavy chains (the building blocks of antibodies) may be secreted in isolation: κ- or λ-light chains or any of the five types of heavy chains (α-, γ-, δ-, ε- or μ-heavy chains).

Additional findings include: a raised calcium (when osteoclasts are breaking down bone, releasing calcium into the bloodstream), raised serum creatinine due to reduced renal function, which may be due to paraprotein deposition in the kidney.

mm

MRI is potentially useful for imaging multiple myeloma because of this modality’s superior soft-tissue resolution. The typical MRI appearance of a myeloma deposit is a round, low signal intensity (relative to muscle) focus on T1-weighted images, which becomes high in signal intensity on T2-weighted sequences. Images 5-7 demonstrate the appearance of a typical myeloma lesion in the proximal humerus. Myeloma lesions tend to enhance somewhat with gadolinium administration. In addition, diffuse areas of replacement of the normal fatty marrow may be seen, resulting in large regions of low T1-weighted signal.

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving  or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

Degree of Confidence

Unfortunately, almost any musculoskeletal tumor has the same signal-intensity profile and enhancement pattern as myeloma. MRI, although sensitive to the presence of disease, is not disease specific. Additional tests must be employed to diagnose myeloma, such as measurement of gamma-globulin levels and direct aspiration of bone marrow to assess for plasmacytosis. Because of this, MRI may understage or overstage patients with myeloma.

In patients with extraosseous lesions, MRI may be useful to define the degree of involvement and to evaluate for cord compression.

The workup of suspected multiple myeloma includes a skeletal survey. This is a series of X-rays of the skull, axial skeleton and proximal long bones. Myeloma activity sometimes appear as “lytic lesions” (with local disappearance of normal bone due to resorption), and on the skull X-ray as “punched-out lesions” (pepper pot skull). Magnetic resonance imaging (MRI) is more sensitive than simple X-ray in the detection of lytic lesions, and may supersede skeletal survey, especially when vertebral disease is suspected. Occasionally a CT scan is performed to measure the size of soft tissue plasmacytomas. Bone scans are typically not of any additional value in the workup of myeloma patients.

Treatment for multiple myeloma is focused on disease containment and suppression. If the disease is completely asymptomatic (i.e. there is a paraprotein and an abnormal bone marrow population but no end-organ damage), treatment may be deferred.

In addition to direct treatment of the plasma cell proliferation, bisphosphonates (e.g. pamidronate or zoledronic acid) are routinely administered to prevent fractures and erythropoietin to treat anemia.

Initial therapy

Initial treatment of multiple myeloma depends on the patient’s age and comorbidities. In recent years, high-dose chemotherapy with hematopoietic stem-cell transplantation has become the preferred treatment for patients under the age of 65. Prior to stem-cell transplantation, these patients receive an initial course of induction chemotherapy. The most common induction regimens used today are thalidomidedexamethasone, bortezomib based regimens, and lenalidomide–dexamethasone. [7] Autologous stem cell transplantation, the transplantation of a patient’s own stem cells after chemotherapy, is the most common type of stem cell transplantation for multiple myeloma. It is not curative, but does prolong overall survival. Allogeneic stem cell transplantation, the transplantation of a healthy person’s stem cells into the affected patient, has the potential for a cure, but is only available to a small percentage of patients. Furthermore, there is a 5-10% treatment-associated mortality rate.

Patients over age 65 and patients with significant concurrent illness often cannot tolerate stem cell transplantation. For these patients, the standard of care has been chemotherapy with melphalan and prednisone. Recent studies among this population. suggest improved outcomes with new chemotherapy regimens. Treatment with bortezomib, melphalan and prednisone had an estimated overall survival of 83% at 30 months, lenalidomide plus low-dose dexamethasone an 82% survival at 2 years and melphalan, prednisone and lenalidomide had a 90% survival at 2 years. Head-to-head studies comparing these regimens have not been performed.

External links

Soucre
http://en.wikipedia.org/wiki/Multiple_myeloma
http://www.emedicine.com/Radio/topic460.htm
http://radiology.rsnajnls.org/cgi/reprint/201/1/243
http://www.ncbi.nlm.nih.gov/pubmed/1110582?dopt=Citation
http://caonline.amcancersoc.org/cgi/content/full/57/5/301
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9 thoughts on “multiple myeloma & mri

  1. Pingback: Multiple Myeloma and MRI « The Radiology Portal

  2. An FDA advisory panel said Optimark and Omniscan used in patients with kidney disease could lead to a painful and lethal condition known as Nephrogenic Systemic Fibrosis.

    The panel believes a new warning is needed for these contrast dyes, but they’ve been harming patients for years with little or no attention.

    Read this to see who’s at risk and what can be done: http://mri-nsf.com/?gclid=CO7Z2NDUyZ4CFc5L5QodHzNzrA

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