Multiple
MyelomaIntroduction This bone
marrow cancer develops out of the bone marrow of the long bones (arms and legs),
the vertebral bodies and the skull bone. This is the most common bone cancer.
Most patients are older than 40 years. This tumor is slightly more common in males
(1.6 fold) than females. Blacks are affected twice as commonly than whites. It
develops out of B-lymphocytes, which are the antibody producing immune cells originating
in the bone marrow. These cells multiply and produce abnormal antibodies, which
are highly visible on a blood test called serum protein electrophoresis. An
abnormal M spike shows up on this test. In the past this protein was called Bence
Jones protein (now " M protein") and this term is still used today.
This circulating protein is also secreted into the urine and can be detected there.
It causes kidney damage and finally kidney failure.
Symptoms Unexplained
bone pains in the back or chest cage should alarm the physician to the possibility
of multiple myeloma. Kidney failure may be asymptomatic in the beginning,
but would show up on blood tests (elevated BUN and creatinine). However, nighttime
urination("nocturia") due to an inability of the patient's kidneys to
concentrate the urine during the night, could be one of the symptoms. As the kidney
function deteriorates, symptoms of lassitude, lack of concentration and fatigue
are setting in. Anemia occurs as a result of the suppression of the normal B cells
in the bone marrow. This leads to weakness and fatigue as well. Recurrent
bacterial infections are common as a result of a loss of normal immune cell function.
Also common are compression fractures of the vertebral bodies pathological fractures
of the long bones and of the arms and legs. This occurs as the bone structure
is changed from the clusters of multiple myeloma cells, which have been termed
long time ago as "plasmacytoma" lesions by the pathologists. Wherever
a plasmacytoma lesion is found the bone structure is weakened and normal day to
day activities suddenly lead to pathological fractures. In the skull plasmacytoma
lesions can also be found with multiple myeloma and X-rays of the skull would
detect these typical lesions.
Tests The
physician makes the diagnosis based on blood tests, X rays and biopsy tests. The
serum M protein on serum protein electrophoresis is very suggestive of multiple
myeloma. X-rays of bones that are painful may show either the punched-out lytic
lesions or diffuse osteoporosis. Bone marrow biopsy or bone marrow aspiration
can directly lead to a histological diagnosis. Due to the patchiness of multiple
myeloma it may be difficult in the beginning of the disease to hit one of the
plasmacytoma lesions with these tests.
Treatment Multiple
myeloma is a progressive disease, but progression can be delayed significantly
with attention to detail and interventional therapy tailored to the needs of the
patient. The overall survival is 2.5 to 3 years, but depending on the extent of
the disease at diagnosis this can be modified significantly, in some cases with
survivals of up to 10 to 20 years. Generally speaking poor prognostic indicators
at the time of the initial diagnosis are: high levels of M protein in serum or
urine, diffuse bone lesions, anemia, high blood calcium levels and renal failure.
All of these parameters are basically signs that the disease has spread all over
the body, that there is a higher mass of total tumor cells in the body, which
has already led to bone marrow suppression (anemia, higher infection rates, increased
serum calcium levels) and the resulting high M protein has already led to kidney
damage. This would be the equivalent of a stage IV cancer. The hematologist
would do some thorough initial testing prior to chemotherapy to evaluate what
stage the patient is in. Treatment consists of some non specific
measures such as rehydration and increasing physical activity of the
patient. This will help kidney perfusion and help in bringing down the hypercalcemia
(= high blood calcium level). It might be necessary to give occasional palliative
radiotherapy treatments to foci of pain to control the underlying plasmacytomas.
This controls the pain and often changes a bone destroying (osteolytic) lesion
into a bone producing(osteoblastic) lesion. There is then a lesser chance of a
pathological fracture. The patient is also easier to mobilize as the bone pain
typically subsides with focal radiation. For the same reason all patients should
receive pamidronate (brand-name"AREDIA") once per month as a slow intravenous
perfusion and diluted in 500 cc of normal saline, given over at least 4 hours.
This will lessen bone pain, prolong complications due to fractures that are now
less frequent, lower analgesic use and prolong survival. Prednisone is used in
doses of 60 to 80 mg per day to control hypercalcemia. Occasionally high
uric acid levels are a problem from high cell turnover and this can be controlled
by using allopurinol in doses of 300mg per day. Infection is controlled by specific
antibiotic therapy when bacterial infections have been identified and bacteria
have been isolated by cultures. On the other hand occasionally there might be
a need for prophylactic intravenous immunoglobulin when chemotherapy has led to
extremely low white blood cells in the blood. Anemia is treated with packed red
blood cells. In case of a renal cause of anemia the physician may use human recombinant
erythropoietin, which is a hormone that stimulates red blood cell production very
effectively thus reversing the anemia. Specific treatment
consists of chemotherapy, which will decrease the M protein and stabilize the
disease. Alkylating agents such as melphalan and cyclophosphamide have lead to
a median survival extension by a factor of 3- to 7-fold. Prednisone is given intermittently
along the chemotherapy to protect the normal bone marrow. Both chemotherapeutic
drugs lower the white blood count and the platelet count, which makes it important
to monitor these by blood tests about 2 weeks after initiation of chemotherapy
to avoid life threatening complications of infection or bleeding. The orchestration
of this complex therapy requires close cooperation of the patient with a dedicated
hematologist. Regular follow-up visits are required and frequent blood tests to
strike a balance between controlling the multiple myeloma and yet maintaining
vital body functions thus minimizing the cytotoxic side-effects of the chemotherapeutic
agents. |
