Multiple myeloma is a rare form of bone marrow cancer that primarily occurs in older adults. It accounts for 1% of all cancers and 10% of hematological cancers. The incidence is approximately four cases per 100,000 people. In Turkey, an average of around three thousand multiple myeloma diagnoses are made each year.
B-lymphocytes, the main cells responsible for defense in our immune system, transform into plasma cells when they encounter microorganisms, producing substances called antibodies (immunoglobulins, Ig). Multiple myeloma is a disease of blood cells that secrete proteins such as IgG, IgA, or light chains, known as M proteins. However, in multiple myeloma, plasma cells proliferate uncontrollably, producing excessive amounts of a single type of immunoglobulin. Additionally, levels of other types of immunoglobulins decrease dangerously, making patients more susceptible to infections.
In addition to this situation, these rapidly proliferating cells (cancer cells) accumulate in the bones and bone marrow, forming masses that destroy bone tissue. Over time, these tumor masses can lead to the weakening or fracturing of bones and a decrease in the body's resistance to infections. The emergence of myeloma, which is typically seen in individuals over 60 years of age, is facilitated by exposure to chemical substances, antigens, and infections throughout life. Myeloma, which is an adult disease, is not seen in children.
Anyone over the age of 40 who presents with back pain, lumbar pain, kidney failure, or fatigue should undergo differential diagnosis tests for multiple myeloma.
Most patients with multiple myeloma present with unexplained back or bone pain, fatigue, and lung infections. Typically, unexplained bone pain and/or pathological fractures (which are the presenting complaints of 26-34% of patients) in individuals over 60 should raise significant suspicion for this disease. Patients often consult physiotherapists, orthopedists, and sometimes internists and general practitioners due to their pain. Since the majority of these patients are older, they are often diagnosed with osteoarthritis and treated with pain relievers. While these painkillers may reduce the severity of pain to some extent, they can also lead to the emergence of kidney disorders or exacerbate existing ones.
Patients frequently experience complaints related to high calcium levels, such as fatigue, nausea, drowsiness, and increased thirst. Some patients consult nephrology units for kidney failure complaints, while others may seek physiotherapy or orthopedic departments for back pain, and some may present with anemia-related fatigue, easy fatigability, and pallor to internal medicine or hematology specialists. Due to the immune deficiency associated with this disease, other reasons for consulting a physician may include febrile illnesses (often lung and urinary tract infections).
Symptoms and Frequencies (%)
While myeloma is more commonly seen after age 60, it is also frequently encountered in individuals aged 40 to 60 in our country. However, it is rarely observed in individuals under 40. Although the disease is seen more frequently in some families, genetic predisposition is not among the known causes.
As of today, the exact causes of multiple myeloma (MM) have not yet been fully determined. However, commonly suspected factors include exposure to petroleum, chemicals, and radiation therapy.
Research conducted so far has not established a direct link between diet and MM; however, it has been observed to occur more frequently in individuals who consume high amounts of animal fats and in those who are obese. Conversely, those who consume more vegetables, fish, and additional vitamin C are reported to have a lower incidence.
Occupational or Environmental Factors:
Occupational exposures (with weak or unproven associations for most factors listed below, except for nuclear industry):
Other Possible Risk Factors:
Approximately 10% of patients are diagnosed incidentally. Most of these patients are referred to a hematology specialist after a high sedimentation rate is detected. However, there may be delays in referrals for those with kidney failure or lung infections.
Patients with kidney failure often seek medical attention only after becoming dependent on dialysis. If a diagnosis can be made early in these patients, treatment can be administered without the need for dialysis.
The diagnosis of multiple myeloma is not made with a single examination method. To establish the initial diagnosis, tests including sedimentation rate, total protein, albumin levels, and the levels of immunoglobulins (IgG, IgA, IgM) secreted by plasma cells are evaluated through protein electrophoresis. Immunoglobulin levels can increase due to various reasons, but the critical factor is determining whether this increase is related to myeloma. This differentiation can be made through serum and/or urine protein electrophoresis. A uniform increase in immunoglobulins indicates myeloma. If suspicion for MM remains based on the test results, a bone marrow biopsy is performed for further investigation.
During bone marrow aspiration, the number of plasma cells in the bone marrow is assessed. Since the primary site of the disease is the bone marrow, the number of plasma cells increases. Normally, plasma cells constitute about 1-2% of the bone marrow, but in multiple myeloma, this percentage exceeds 10%.
Another diagnostic method involves examining lytic lesions in the bones. These are detected as images resembling punctured areas in radiological bone scans.
In summary, the key diagnostic criteria are the increase of plasma cells in the bone marrow, the level of immunoglobulins, and the presence of lytic lesions in the bones.
Another symptom observed in these patients is the impairment of kidney functions. The proteins secreted by myeloma cells disrupt kidney functions, leading to elevated urea levels in patients. Consequently, these individuals are classified as kidney patients and may undergo dialysis treatment.
For patients under 65, if their organ functions are adequate, chemotherapy followed by autologous transplant is the standard treatment after reducing M-protein levels.
In these patients, the presence of anemia, the level of calcium in the blood, the prevalence of lytic lesions in the bones, the level of immunoglobulins, and the levels of CRP, albumin, and LDH provide clues about the stage of the disease and its progression. The disease is classified into three stages. In the past, it was estimated that those in the early stage could live up to 10 years, those in the intermediate stage could live 2-10 years, and those in the advanced stage could live about two years; today, 30% of patients are projected to have a 10-year survival rate.
General Overview of Disease Staging:
The staging of the disease is a significant step that greatly assists in determining clinical treatment. Based on the information gathered at this stage, each physician aims to choose the most beneficial and appropriate treatment plan for their patient.
Treatment options should be determined based on each patient's overall condition, complaints, and the stage of the disease. For this reason, patients who do not have any symptoms or complaints are monitored through evaluations of their general health and disease status. In contrast, patients with complaints and those with progressive disease are primarily treated with medication (chemotherapy). Chemotherapy achieves complete remission in 10-50% of patients and partial clinical improvement in 50-70% of patients.
In patients younger than 65 years without organ dysfunction, autologous (from their own tissue) transplantation is applied as standard treatment. Before stem cell transplantation, chemotherapy is administered to reduce the disease to the lowest possible level. Then, autologous stem cell transplantation is performed. The risk of mortality in autologous transplantation is found to be below 3%. If the patient is over 65 years old or cannot undergo autologous transplantation due to impaired organ function, combination chemotherapy with three or two agents is administered. If there are heart or lung function issues, the patient may lose the chance for autologous transplantation. Impaired kidney function does not constitute a barrier for autologous transplantation; however, if the patient becomes dependent on dialysis, autologous transplantation is not recommended.
In recent years, with technological advancements, drugs that can directly kill myeloma cells without damaging healthy cells have begun to be used in older patients who cannot undergo autologous bone marrow transplantation.
In addition to all the aforementioned treatment options, adjunctive treatment methods also play a role in the treatment of multiple myeloma. Radiation therapy may be provided to reduce pain in bones that are highly painful and/or at high risk of fracture to prevent complications. Oral medications are also used to prevent complications arising from bone architecture degradation. If pathological fractures develop despite all efforts, immediate surgical intervention is performed on the fracture.
As previously mentioned, additional issues such as anemia and febrile illnesses due to immune system impairment that affect patients' overall conditions and quality of life can be managed with supportive treatments. Erythrocyte transfusions or the administration of substances that stimulate red blood cell production (erythropoietin), as well as appropriate antibiotic treatment when necessary, constitute a significant portion of supportive treatment options.
Since the risk factors that lead to multiple myeloma have not yet been fully identified, it can be said that avoiding environmental factors and occupational risk factors, as well as maintaining a healthy and balanced diet with regular health check-ups, are valid methods for prevention.
Especially for individuals over 50 years old, if they frequently experience infections, bone pain, frequent nosebleeds, prolonged bleeding from minor cuts, easy bruising, and complaints of abnormal fatigue, they should be advised to consult a doctor without delay.
Regular health check-ups are of great importance for early diagnosis.
Last Updated Date: 07 September 2016
Publication Date: 11 August 2016
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