Symptoms of Multiple Myeloma

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Symptoms of Multiple Myeloma

Myeloma represents tumour cells (hematological neoplasm), a subtype of white blood cells that form antibodies (which are immunoglobulins), which are essential to protect the body from infections. In this article, we will give you a complete guide about the symptoms of multiple myeloma.

There are five types of immunoglobulins: A, G, M, D, and E. The plasma cells are present in the bone marrow, located within the bone structure of the skull, pelvis, vertebrae, ribs; the bone marrow is responsible for producing all blood cells (red blood cells, white blood cells and platelets). Plasma cells can transform into cancer cells based on not fully known events. In this case, the plasma cell will no longer produce the 5 types of immunoglobulins but only one (monoclonal plasma cell), which will have a proliferative advantage over the others, consequently reducing. Multiple myeloma; less frequent forms are the small molecular myeloma, the non-secretory myeloma, the solitary plasmacytoma and myeloma indolent.  By stimulating osteoclasts’ activity, the myeloma tumour plasma cells create lesions in the skeleton’s bones that can also cause fractures.

Symptoms of Multiple Myeloma

For further information:  Multiple Myeloma Symptoms

Age of Onset

Multiple myeloma occurs mainly in old age (over 50 years).

Multiple Myeloma Symptoms: How Does It Occur?

Signs and symptoms can vary greatly from person to person, as many organs can be affected by the disease. At the onset, the condition may not cause any symptoms. As the disease progresses, symptoms related to plasma cell infiltration of organs and excessive production of monoclonal immunoglobulins are likely to occur:

  • Bone pains. Bone pain affects nearly 70% of patients with multiple myeloma and is the most common symptom. The initial symptoms are “pseudorheumatic”, while acute and persistent localized pain could indicate a pathological bone fracture. Involvement of the vertebrae can lead to compression of the spinal cord. In multiple myeloma, bone damage is secondary to the appearance of “lytic” type lesions and osteopenia related to the proliferation of myeloma plasma cells in the medullary cavity. Multiple myeloma cells, in fact, produce various factors (grouped under the name OAF, Osteoclast Activating Factor s) that allow osteoclasts to accelerate the demolition of bone tissue by resorption. This alters the tissue structure, making the bones fragile and prone to fractures,  osteoporosis and crushing (vertebrae). From the radiological point of view, the bone rearrangement is evident due to the appearance of “perforated” spots, which coincide with the areas in which osteocondensation is absent. The increase in bone lesions can also increase the release of calcium into the blood ( hypercalcemia ).
  • Hypercalcemia. A high level of calcium in the blood affects nerve function and causes excessive thirst,  nausea,  constipation,  loss of appetite and mental confusion. Hypercalcemia is due to the infiltration of malignant cells into the bones.
  • Kidney failure. Several factors are involved in influencing renal function. High levels of abnormal monoclonal immunoglobulins (M proteins ) can cause tubular lesions following their deposit in the glomeruli  (Bence Jones proteinuria).

Other signs and symptoms of multiple myeloma

  • Infections: Reducing white blood cells (leukopenia) leads to immune deficiency and lower resistance to diseases. These can be of varying clinical severity ( pneumonia, sinusitis, skin, bladder or kidney infections) and are the leading cause of death in patients with multiple myeloma. The period of the most significant risk for the onset of conditions includes the initial months after chemotherapy.
  • Alterations in haemostasis: the lack of platelets (thrombocytopenia) causes alterations in the coagulation process, which manifests itself with a marked tendency to bleeding—other abnormalities of haemostasis result from reduced fibrinolysis.
  • Hyperviscosity syndrome: in some cases of multiple myeloma, there is an increase in the value of plasma viscosity, which determines hemorrhagic symptoms of multiple myeloma, neurological disorders and coronary ischemia.
  • Neurological Disorders: The neurological manifestations associated with multiple myeloma are heterogeneous. The appearance of neuritic pains and limb weakness or numbness are the most common symptoms of multiple myeloma. Finally, there may be radicular pain and compression of the spinal cord due to vertebral involvement, carpal tunnel syndrome, and other neuropathies caused by amyloid deposits’ infiltration in the peripheral nerves.
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Anemia and infections

Anemia is a drop in the number of red blood cells in the blood. It is a common symptom in people with myeloma. It can make you feel exhausted, and you may even feel short of breath. Myeloma can reduce the number of red blood cells produced in the bone marrow.

In this case, the doctor may propose blood transfusions. If you already have a venous catheter, blood is infused through that, otherwise into a vein in your arm. If kidney problems are present, your doctor may suggest erythropoietin, a drug that stimulates the bone marrow to produce red blood cells, instead of a blood transfusion.

In some cases, myeloma and some treatments can also reduce the number of white blood cells, which help the body fight infections. The doctor may also prescribe prophylactic drugs to prevent disease or recommend vaccines (such as the flu shot).

Kidney problems: Symptoms of Multiple Myeloma

The paraprotein and light chains produced by myeloma can prevent the kidneys from properly filtering the blood. Calcium buildup from weakening bones can also cause kidney problems. To prevent kidney problems, it is advisable to drink plenty of water, preferably three litres a day. Consult your doctor before taking non-steroidal anti-inflammatories.

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Suppose kidney damage is judged to be severe, which is actually quite rare. In this case, we speak of acute renal failure. The flow of urine stops, and fluids begin to accumulate in the body. It will then be necessary to filter the blood through a machine through the dialysis procedure.

Hyperviscosity syndrome

In rare cases, myeloma causes a very marked rise in the levels of paraprotein in the blood. This means that the blood can become thicker than usual. We, therefore, speak of hyperviscosity syndrome. Symptoms of multiple myeloma can be headache, lightheadedness, dizziness, vision problems, and bleeding. It may be necessary to plasmapheresis, a procedure that helps to eliminate excess paraprotein in the blood.

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DIAGNOSIS: Symptoms of Multiple Myeloma

When faced with a suspicious clinical picture (chronic pain or spontaneous fracture), the doctor requests blood and urine tests. These are the task of assessing whether there is an increase in the production of an abnormal immunoglobulin (monoclonal component) in the blood and urine if there is anemia, signs of renal failure, and hypercalcemia.

The support of imaging diagnostics (radiography, low-dose CT scan, possibly magnetic resonance imaging ). It helps in defining the diagnosis of myeloma by confirming the presence of lytic lesions or pathological fractures. It is vital to specify that the presence of monoclonal immunoglobulins, if not exceptionally high and as the only laboratory data, do not indicate the presence of myeloma but may be suggestive of a “premieloma” condition (called MGUS – monoclonal gammopathy of uncertain significance), which does not require any treatment but only periodic laboratory checks. This condition is quite common in the elderly and only rarely develops into frank myeloma.

RISK FACTORS

The causes of this tumour are not yet fully known, even if recent studies have highlighted anomalies in the structure of chromosomes and some specific genes in patients affected by the disease. Age is the leading risk factor for multiple myeloma: over two-thirds of diagnoses are in people over 65 and only one per cent in people under forty. Furthermore, the risk of getting this type of cancer is higher in men than in women.

Exposure to radioactivity and family history could be risk factors. But these are conditions that affect a small number of cases. Even obesity and exposure to substances present in the oil industry operations may constitute risk factors. In no case is it possible to establish specific prevention strategies for myeloma. It is good practice to keep the bodyweight under control. And avoid exposure to carcinogens that could increase the risk—people with other plasma cell diseases. MGUS (monoclonal gammopathy of uncertain significance) or indolent myeloma cannot implement preventive measures to prevent the pathologies from progressing and degenerating into myeloma if not strictly following the check-up schedule.

Treatment

To know more:

Multiple Myeloma Medicines

Treatment of multiple myeloma focuses on therapies that reduce the clonal population. If the disease is completely asymptomatic, management is limited to clinical observation. If multiple myeloma symptoms are present, treatment can help relieve pain, control complications, stabilize the condition, and slow tumour progression.

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First-line therapy: Symptoms of Multiple Myeloma

In recent years, high-dose chemotherapy treatment with autologous hematopoietic stem cell transplantation ( autotransplantation ) has become the most suitable therapeutic option for patients under 65. The most commonly used regimens include the administration of thalidomide (+  dexamethasone ),  bortezomib, and lenalidomide  (+  dexamethasone). Treatment with high-dose chemotherapy and stem cell support (autograft) is not curative but can prolong overall survival and lead to complete remission.

Allogenic stem cell transplantation, that is, from a healthy person to the affected patient. It represents a potential cure but is only available for a small percentage of clinical cases. Patients over 65 and with significant concomitant disease often cannot tolerate stem cell transplantation. Standard treatment usually involves chemotherapy with melphalan (for 4-7 days) combined with prednisone for these people. (5-10 days), in cycles repeated every 6 weeks, followed by a rest period.

In some patients, the association of this protocol with new therapeutic regimens. Including, for example, the administration of bortezomib may be useful. This drug is a proteasome inhibitor (a multiprotein complex present in all cells), which allows for complete clinical responses in patients with refractory or rapidly progressing disease. The action of bortezomib is based on the induction of apoptosis in tumour cells by blocking proteasomes’ action.

Supportive therapy

In addition to the direct treatment of multiple myeloma,  bisphosphonates  (e.g. pamidronate or zoledronic acid ) are regularly administered to control lytic lesions and prevent bone fractures. While the administration of platelet concentrates can stop bleeding determined by thrombocytopenia. Steroids and bisphosphonates are also important in the treatment of hypercalcemic crises. In contrast, antibiotics are supportive of the management of infections.

HOW IT IS CARED FOR

The choice of therapy depends on the tumour’s size and stage, the patient’s age, and general conditions. It is, in any case, the result of a multidisciplinary evaluation.

Surgery: Symptoms of Multiple Myeloma

Surgery is mainly used to stabilize a spinal column damaged by the disease or in cases of spinal compression, which can result in paralysis or excessive weakness. Rarely, it may be possible to remove the myeloma when it occurs only in a plasmacytoma form.

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Chemotherapy

It is one of the treatments used in myeloma and involves administering drugs, orally or intravenously, to destroy the cancer cells directly. It is generally used in combination with new immunomodulating drugs. That does not act now on myeloma cells but rather on the bone marrow microenvironment that supports them.

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Radiotherapy: Symptoms of Multiple Myeloma

It can be used to treat myeloma and consists of radiation usually aimed at the tumour site to destroy cancer cells without damaging healthy ones. It has a palliative effect and can compromise a possible neurosurgical procedure.

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Stem cell transplantation

The discovery of the presence in the bone marrow of the well-known stem cells. Capable of giving rise to a new marrow, it has made an enormous contribution to myeloma treatment. In fact, to treat patients with high-dose chemotherapy, it is necessary to eliminate cancer cells.

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This can be done through the transplantation of stem cells taken from the patient himself (autologous transplant), which, after being treated and cryopreserved, can be reinfused after the myeloablative chemotherapy treatment. Indeed, it is now standard practice to take stem cells either from the patient’s own blood ( autologous transplant ) or from the bone marrow of an external donor (allogeneic transplant ) and use them for a renal transplant sick person.

Conclusion

According to the data reported in the volume “Cancer numbers in Italy”, written by the Italian Association of Medical Oncology (Atom) and by the Italian Cancer Registry (Airtum). Approximately 4300 new cases of the disease counted every year in Italy (with a slightly higher incidence in men). The incidence rates are fairly constant over time and in the regional distribution. The mean age of diagnosis is 68 years.

Consultancy:  Sergio Siragusa, head of the hematology unit at the Giaccone polyclinic and full professor of hematology at the University of Palermo.

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