myeloma | Multiple myeloma

Multiple myeloma



Multiple Myeloma of Bones (also known as Kahler disease, Kahler-Bozzolo1 disease, or, simply, myeloma) is a hematologic cancer (meaning that it develops from the cells of the hematopoiesis, the same ones that are at The origin of the blood cells, formed in the bone marrow).

The affected cells are plasma (which are terminally differentiated B lymphocytes), immune system cells that produce antibodies (immunoglobulins) to fight infections and diseases. Myeloma is a disease characterized by the development in the skeleton of multiple tumours osteolytic to plasma (plasmacytomas) In most cases secreting either a monoclonal immunoglobulin type G (52% of cases) or a type a (21% of A Kappa or LAMBDA light chain (12%).

Epidemiology
In France, the incidence is 4 000 cases per year. In the United States, 45 000 people live with myeloma with about 20 000 new cases per an2. Its impact tends to increase. It is more common in Afro-américains3 and rarer in CHINA2. In Canada, approximately 2 000 people are diagnosed with multiple4 myeloma each year.

After diagnosis, survival without incident is estimated at 5 months, total survival at 56MOIS5.

Myeloma is the second most common hemopathy (10%) after non-Hodgkin's lymphoma. It accounts for about 1% of all cancers and 2% of all cancer deaths.

The average age of myeloma onset is 65 to 70 years, but tends to decrease.

Myeloma affects a little more men than women.

The causes of multiple myeloma are poorly understood. Exposure to certain organochlorines (e.g. Chlordecone used as a pesticide) appears to be one of the risk factors. For example, in Martinique, an analysis of the risk of cancer (by zones) controlled by the InVS concluded that a "statistically significant overincidence of Multiple6 myeloma" was found in adult men living in the area where the chlordecone was most used and Would still be the most present in soils (according to the BRGM). In addition, the incidence-of-myeloma gradient was increasing gradually from the supposedly least polluted areas to those potentially plus6.

Diagnosis
Diagnosis circumstances
Multiple myeloma is often randomly detected during a routine blood test.

The most common symptoms guiding this biological discovery are:

Bone pain or pathological fractures (spontaneous or after too little stress) 7.8;
A asthenia, which may be related to anemia, hypercalcemia or renal failure;
tingling in extremities and neuropathic pains.
Biological diagnosis
The main consequence of myeloma is the presence of a very large amount of immunoglobulins in the blood. These immunoglobulins are proteins, which are manifested by:

Elevation of sedimentation velocity;
a hyperprotidémie;

A peak in the gamma-globulins zone with serum protein electrophoresis in the complete chain forms. The immunofixation is used to prove the monoclonal character of the spike (i.e., derived from the same tumor clone of plasma). In light chain forms, a hypogammaglobulinemia is observed, with the amount of light chains almost never sufficient to show a visible monoclonal peak.
Hypercalcemia, frequent, is related to bone destruction.

Excess protein is also found in the urine; This proteinuria consists of light chains of monoclonal immunoglobulins, also known as Bence-Jones protein. The immunoelectrophoresis or immunofixation of urinary proteins determines the type of chain, kappa or lambda. This peak is detected in the Bêtaglobulines.

Benign monoclonal Gammapathie does not include anemia, bone injury, or viscérale9 complication. As the name implies, it does not have the same severity as the myeloma and requires mere monitoring.

Other exams

Myelogram studies bone marrow cells, collected by puncture, in search of excess plasma. In myeloma, the marrow is infiltrated by plasma, which usually present numerous morphological anomalies and are frequently in mitosis.

The skeletal X-rays show very frequently bone lesions to the type of osteolysis.

Evolution and Complications
Myeloma is a serious disease. However, there are forms with a low tumor mass, which can remain asymptomatic (without apparent signs) for years.

Myeloma can be complicated:

of infections; Indeed, the presence of an immunoglobulin in very large quantities inhibits the normal synthesis of other immunoglobulins, which no longer allows the body to cope with infectious agents, which are a major cause of death;
Bone disorders: pain, fractures, vertebral settlement, etc.
Renal failure, especially in the case of light chain proteins;
Neurological disorders: Compression of the spinal cord after a vertebral settlement, nerve impairment, épidurite;
of microcytic anemia and thrombocytopenia (decrease in the number of blood platelets that can cause hemorrhage), by multiple mechanisms, including medullary failure: Production deficiency by the marrow.
The stratification of the disease can be done according to different criteria. that of Durie and Salmon10 was used until 2005. It was replaced then by a INTERNATIONALE11 classification.

Treatment
The classic treatment of myeloma has long been based on chemotherapy for cases of active disease, most often (since the years 1960) of Melphalan and corticosteroids. Today, new therapies, called "targeted therapies", have completely altered the management of multiple myeloma (BORTÉZOMIB12 or Velcade, Thalidomide13, doxorubicin liposomal pegylée or Caelyx, and lenalidomide or Revlimid). Thalidomide is given first-line in association with Melphalan and prednisone. Lenalidomide is given in second intention in association with dexamethasone for refractory forms or in the case of relapse after at least one therapeutic line with alkylating and where no alternatives exist. Lenalidomide is recognized worldwide as one of the most effective drugs in association for the treatment of multiple myeloma. It is also a treatment that prolongs the lives of patients and, in many cases, allows them to retain fully and actively an insertion in their collectivité4,14. Bortezomib is potentially used at several stages of the disease, particularly in the first line associated with thalidomide and Melphalan.

Treatment may be avoided if the myeloma is at a very low stage.

It is also necessary to combat bone pain, hypercalcemia, and to treat complications if necessary. Bisphosphonates are used against bone lysis and have a clean action against MYÉLOME15.

Since the end of the years 1990, the techniques of self-grafting of stem cells have been favoured, consisting in the removal of stem cells that are "cleaned" of the cells carrying the disease and that they are frozen and then put the patient in aplasia (destruction Total plasma). The stem cells are then reinjected, which will regenerate "healthy" plasma. The results are very favorables16. This technique can be repeated, especially in the case of incomplete response of the first autogreffe17, the average survival exceeding the seven ans18.

Prognosis
The international staging system can help predict the duration of survival that depends on the disease phase.