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Multiple myeloma
ICD9 = 203.0| }} Multiple myeloma (also known as MM, myeloma, plasma cell myeloma, or as Kahler's disease after Otto Kahler) is a malignant neoplasmof plasma cells, the cells of the immune systemthat produce antibodies. Its prognosis despite therapy is generally poor, and treatment may involve chemotherapyand stem cell transplant. It is part of the broad group of diseases called hematological malignancies.
Signs and symptomsSymptoms can include: malaise, bone pain, anemia, infections(due to decreased immunity) and fractures(due to breakdown of bone by malignant cells, as well as a tendency to brittle bones)[1]. Often, the diagnosis of multiple myeloma is made incidentally during routine blood testsfor other conditions. The antibody that is produced in excess may cause specific medical problems, such as amyloid, acute renal failureand chronic renal failure, polyneuropathyand other disorders. A mnemonicdoctorsuse to remember the common tetrad of multiple myeloma is CRAB - C = Calcium (elevated), R =Renal failure, A = Anemia, B = Bone lesions[2]. DiagnosisInvestigationsThe existence of unexplained anemia, kidneydysfunction, a high erythrocyte sedimentation rate(ESR) and a high serum protein(especially raised immunoglobulin) may suggest further testing. A doctorwill then order protein electrophoresisof the blood and urine, on which a paraprotein(monoclonal protein, or M protein) band may be noticed. A type of paraprotein is the Bence Jones proteinwhich is paraprotein composed of free light chains (see below). Quantitative measurements of the paraprotein are necessary to determine the severity of the disease. The paraprotein is a deviant immunoglobulinproduced by the tumor clone. Very rarely, the myeloma is nonsecretory (not producing immunoglobulins). In theory, myeloma can produce all classes of immunoglobulin, but IgD, and IgE myeloma are very rare compared to IgG and IgA and to a lesser extent IgM, . 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 are: a raised calcium(when myeloma cells are breaking down bone, releasing calcium into the bloodstream) and decreased renal function, which may be due to paraprotein deposition in the kidney). WorkupThe workup of suspected multiple myeloma includes a skeletal survey. This is a series of X-raysof 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). A CT scanmay be performed to measure the size of soft tissue plasmacytomas. A bone marrow biopsyis usually performed to estimate the percentage of bone marrow occupied by plasma cells. This percentage is used in the diagnostic criteria for myeloma. Immunohistochemistry(staining particular cell types using antibodies against surface proteins) can detect plasma cells which express immunoglobulin in the cytoplasm but usually not on the surface; myeloma cells are typically CD56, CD138 positive and CD19 negative[2]. Cytogeneticsmay also performed in myeloma for prognostic purposes. Other useful laboratory tests include quantitative measurement of IgA, IgG, IgM and ?2-microglobulin. The recent introduction of a commercial immunoassay for measurement of free light chains potentially offers a significant improvement in monitoring disease progression and response to treatment. Initial research also suggests that measurement of free light chains may also be used, in conjunction with other markers, for assessment of risk of progression from monoclonal gammopathy of undetermined significance(MGUS) to multiple myeloma[citation needed]. CriteriaNew international criteria[2], agreed in 2003, require the following:
Some myelomas do not secrete any paraprotein. These are termed "non-secretory myeloma" with low or undetectable paraproteins on routine serum or urine protein electrophoresis. Measurement of serum free light chains may often be helpful to follow the disease burden in nonsecretory myeloma. It is rare compared to the secretory forms. Related conditions are solitary plasmacytoma (a single tumor of plasma cells, typically treated with irradiation), plasma cell dyscrasia (where only the antibodies produce symptoms, e.g. amyloidosis) and monoclonal gammopathy of undetermined significance(MGUS). Most cases of myeloma probably start as MGUS. StagingInternational Staging System (ISS):
PathophysiologyMultiple myeloma develops in post-germinal center B lymphocytes. A chromosomal translocationbetween the immunoglobulin heavy chain gene (on the fourteenth chromosome, locus 14q32) and a oncogene(often 11q13, 4p16.3, 6p21, 16q23 and 20q11[1]) is frequently observed in patients with multiple myeloma. This mutation results in dysregulation of the oncogene which is thought to be important initiating event in the pathogenesis of myeloma. The result is proliferation of a plasma cell clone and genomic instabilitythat leads to further mutations and translocations. The chromosome 14 abnormality is observed in about 50% of all cases of myeloma. Deletion of (parts of) the thirteenth chromosome is also observed in about 50% of cases. Production of cytokines(especially IL-6) by the plasma cells causes much of their localised damage, such as osteoporosis, and creates a microenvironment in which the malignant cells thrive. Angiogenesis(the attraction of new blood vessels) is increased. The produced antibodies are deposited in various organs, leading to renal failure, polyneuropathy and various other myeloma-associated symptoms. EpidemiologyThere are approximately 45,000 people in the United Statesliving with multiple myeloma, and the American Cancer Societyestimates that approximately 14,600 new cases of myeloma are diagnosed each year in the United States. It follows from here that the median prognosis is about three years[1]. Multiple myeloma is the second most prevalent blood cancer (10%) after non-Hodgkin's lymphoma. It represents approximately 1% of all cancers and 2% of all cancer deaths. Although the peak age of onset of multiple myeloma is 65 to 70 years of age, recent statistics indicate both increasing incidence and earlier age of onset. Multiple myeloma affects slightly more men than women. African Americans and Native Pacific Islanders have the highest reported incidence of this disease and Asians the lowest. Results of a recent study found the incidence of myeloma to be 9.5 cases per 100,000 African Americans and 4.1 cases per 100,000 Caucasian Americans. Among African Americans, myeloma is one of the top 10 leading causes of cancer death. TreatmentTreatment for multiple myeloma is focused on disease containment and suppression. Although allogeneic stem cell transplantmight cure the cancer, it is considered investigational given the high treatment related mortality of the procedure. In addition to direct treatment of the plasma cell proliferation, bisphosphonates(e.g. pamidronate) are routinely administered to prevent fractures and erythropoietinto treat anemia. Initial therapyInitial therapy is aimed at treating symptoms and reducing the burden of disease. Commonly used induction regimensinclude dexamethasonewith or without thalidomide, and VAD (vincristine, doxorubicin(Adriamycin), and dexamethasone). Low-dose therapy with melphalancombined with prednisone can be used to palliate symptoms in patients who cannot tolerate aggressive therapy. In patients who have good performance status, the next step in therapy is high-dose chemotherapywith melphalan with autologous stem cell transplantation. This can be given in tandem fashion, i.e. an autologous transplant followed by a second transplant. Nonmyeloablative allogeneic stem cell transplantis being investigated as an alternative to autologous stem cell transplant. RelapseFrequently, myeloma progresses despite treatment. It has been observed[1] that "treatment resistance" is a reversible effect, and that some new treatment modalities may re-sensitize the tumor to standard therapy. For patients with relapsed disease, bortezomib(or Velcade) is a recent addition to the therapeutic arsenal, especially as second line therapy. Bortezomib is a proteasomeinhibitor. Finally, lenalidomide(or Revlimid), a less toxic thalidomide analog, is showing promise for treating myeloma. It awaits FDAapproval. Renal failure in multiple myeloma can be acute(reversible) or chronic(irreversible). Acute renal failure typically resolves when the calcium levels are brought under control. Treatment of chronic renal failure is dependent on the type of renal failure and may involve dialysis. Which type of renal failure a given patient has is difficult to determine at presentation. PrognosisAdvanced age (age greater than 60), elevated lactate dehydrogenase, and decreased platelets are associated with a poorer prognosis. Cytogeneticsmay also be important for determining prognosis. PatientsSome well-known patients include:
Deceased:
See also
References
External links
fr:Myélome multiple nl:Ziekte van Kahler Categories: Articles lacking sources| Hematology| Oncology
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