From BMT Newsletter
March 1994
Issue # 22 - Multiple Myeloma
Reprinted by NYSERNet with Permission from BMT Newsletter


Multiple Myeloma Resources


	The International Myeloma Foundation publishes a
newsletter and informational brochures about multiple
myeloma, and sponsors support groups and patient
conferences. For information phone 800-452-CURE (outside
the US phone 213-656-5658) or write IMF, 2070 Stanley
Hills DL, Los Angeles CA 90046.

	The Leukemia Society of America publishes an
informational brochure on multiple myeloma, and offers
financial assistance to multiple myeloma patients.  For
information phone your local LSA chapter or the national
office at 800-248-4271, or write the Leukemia Society of
America, 600 3rd Avenue, New York NY 10016.

	BMT Newsletter maintains a list of attorneys who
can help multiple myeloma patient secure insurance
coverage for their BMT. If you need an attorney referral,
phone 708-831-1913.


BMT Newsletter (c) 1994

From BMT Newsletter
March 1994
Issue # 22 - Multiple Myeloma
Reprinted by NYSERNet with Permission from BMT Newsletter

BMTs Hold Promise For Multiple Myeloma Patients


	In 1994, an estimated 13,000 people will be newly
diagnosed with multiple myeloma in the US. Twice as many
African-Americans will be afflicted as whites. Although
often described as a disease of the elderly, 35-40
percent of those diagnosed with multiple myeloma will be
under the age of 60.

	Until recently, multiple myeloma was considered
incurable. Recent research, however, suggests that a bone
marrow transplant (BMT) can significantly prolong the
life of multiple myeloma patients.  Studies are underway
to determine whether BMTs can provide long-term control
or a cure for the disease.

What is Multiple Myeloma?

	Multiple myeloma is a bone marrow cancer that
interferes with production of normal blood cells. Bone
marrow is the soft spongy tissue in long bones that
produces white blood cells, red blood cells and
platelets. White blood cells are needed to fight
infection. Red blood cells carry oxygen from the lungs to
other parts of the body. Platelets enable blood to clot.

	When infectious organisms are detected in the
body, one type of white blood cell - the B-cell - evolves
into a special cell called the plasma cell. Each plasma
cell produces a unique protein or "antibody" that helps
neutralize invading organisms.

	In patients with multiple myeloma, an abnormal
plasma cell replicates itself uncontrollably and
suppresses the growth of normal plasma cells. The cell
usually produces an excessive amount of its unique
protein which is detectable in the patient's blood and/or
urine. The specific protein varies from patient to
patient and is called the "monoclonal protein" or
"M-protein". The level of this protein in the blood
and/or urine is an indicator of the stage or severity of
the disease at any given time.

	The defective plasma cells grow slowly in the
bone marrow, and eventually interfere with the production
of normal blood cells. A decrease in red blood cells
causes anemia. Occasionally, a reduced platelet count in
multiple myeloma patients results in excessive bleeding.


	Multiple myeloma patients often develop
"osteolytic lesions" - painful holes in the bones. When
extensive, osteolytic lesions increase the level of
calcium in the bloodstream, a condition called
"hypercalcemia".

	Plasma cells of multiple myeloma patients also
produce unusual proteins called "Bence Jones" proteins
which may form deposits in the tiny tubules of the
kidneys and cause kidney failure.  Hypercalcemia
contributes to kidney failure since increased levels of
calcium in the bloodstream can cause fluid loss and
dehydration.

	Symptoms of multiple myeloma include bone pain
(often in the lower back), weakness and recurring
infections. Nausea, vomiting, constipation, increased
thirst and urine output, and confusion - indications of
possible kidney failure and/or hypercalcemia -may also be
experienced.  In the early stages of the disease,
however, a patient may experience no symptoms at all.

Stages of the Disease

	The existence and stage of the disease is
determined by removing a sample of bone marrow and
conducting several blood and urine tests. If more than
15% of the blood cells in the bone marrow sample are
plasma cells, multiple myeloma is possible. Blood tests
for calcium and M-protein levels, and urine tests for the
Bence Jones proteins confirm the diagnosis.  X-rays
determine whether osteolytic lesions are present in the
bones.

	Stage I is the earliest phase of the disease.
Although tests confirm the existence of multiple myeloma,
the patient may have no symptoms and the disease may not
progress for many months or a few years.

	Stage II is a more advanced phase of the disease.
Twenty to 40 percent of the cells in the bone marrow are
usually abnormal plasma cells (myeloma cells) which begin
to invade the bones. Blood and urine tests may show an
increased output of calcium and abnormal proteins.

	Stage III is the most advanced stage of multiple
myeloma. Typically more than 50 percent of the cells in
the bone marrow are myeloma cells, and multiple bone
lesions are often present. Patients are usually severely
anemic, their immune system does not function properly
and they have difficulty fighting infections.

Treatment Options

	Melphalan and prednisone, as well as other
combinations of chemotherapy have been used successfully
to achieve a "partial remission" of the disease in
approximately 50 percent of multiple myeloma patients. A
partial remission means that the number of myeloma cells
is significantly reduced, and the level of the M-protein
in the blood and/or urine is reduced 50 to 75 percent. A
"complete remission" of the disease is achieved in only 5
percent of patients. A complete remission means that no
cancerous cells can be detected in the bone marrow, and
no abnormal protein levels are seen in the blood or
urine. Remissions may be maintained for several months or
a few years.

	Achieving a complete remission is believed to be
an important first step toward developing long-term
control and a cure for myeloma. Thus, researchers
have tested whether higher doses of chemotherapy followed
by a bone marrow transplant (BMT) increases the number of
complete remissions achieved and improves long-term
survival rates. The results of these studies, involving
more than 1,000 patients, have been very encouraging.

	Twenty five to 40% of patients achieved complete
remissions following high-dose chemotherapy and a BMT.
This compares favorably with the S percent complete
remission rate achieved when lower doses of chemotherapy
are used.  Moreover, in some studies, patients who
achieved complete remission following high-dose
chemotherapy and a BMT survived longer - in some cases,
twice as long - as those treated with low dose
chemotherapy.

	Most patients involved in these studies underwent
an autologous BMT (ABMT) following high dose
chemotherapy, rather than an allogeneic BMT. In an
autologous BMT, a portion of the patient's own bone
marrow is removed prior to treatment and reinfused
following the high dose chemotherapy. In an allogeneic
BMT, bone marrow from a donor is infused into the patient
following the high dose chemotherapy.

	Autologous BMTs involve fewer complications than
allogeneic BMTs and thus are more easily tolerated by
older patients. Since the majority of multiple myeloma
patients are over the age of 60 and beyond the upper age
limit for an allogeneic BMT, an autologous BMT is usually
the recommended treatment option.

	Autologous BMTs, however, have one major
drawback. Since multiple myeloma is a disease of the bone
marrow, reinfusing t he patient's own bone marrow
following high dose chemotherapy reintroduces some
cancerous cells back into the body. Whether these cells
multiply and eventually cause the disease to recur is not
yet known. Some BMT centers attempt to cleanse or "purge"
autologous bone marrow of cancerous cells before
reinfusing it into the patient. It has not yet been
demonstrated, however, that purging is necessary or
beneficial.

	Other researchers are investigating whether
transplanting "peripheral blood stem cells" instead of
bone marrow improves long term survival rates. Stem cells
are the "mother cells" from which all blood cells evolve.
They may either be collected from the bone marrow or from
the circulating "peripheral" blood.  There may be fewer
cancerous cells in the peripheral blood stem cells than
in the bone marrow of multiple myeloma patients. Thus,
using peripheral blood stem cells rather than bone marrow
may reduce the chance of relapse and prolong survival.
Peripheral blood stem cells used alone or with bone
marrow speeds the recovery of blood counts following high
dose chemotherapy, and may therefore decrease the risk of
infection and bleeding after the transplant.

	Although an allogeneic BMT has more side-effects
(e.g,. graft-versus-host disease) than an autologous BMT,
it may ultimately prove to be more effective in curing
the disease. Since donor marrow is used in an allogeneic
BMT, the problem of reinfusing cancerous cells into the
patient is eliminated. "In general, multiple myeloma
patients who are 55 years old or younger, have a suitable
bone marrow donor, and are in reasonably good health
should consider an allogeneic BMT," advises Ken Anderson
MD, Dana Farber Cancer Institute, Boston MA.

When to Transplant

	Although the optimal time for multiple myeloma
patients to undergo a transplant is still under
investigation, the best results have been seen in
patients who underwent a BMT within a year of their
initial diagnosis while the disease was still sensitive
to chemotherapy. However, even patients who have
undergone a considerable amount of treatment prior to
considering a BMT, and whose disease has become resistant
to standard chemotherapy may benefit from a BMT.

	The type and quantity of chemotherapy
administered to patients early in the course of their
disease can significantly affect both their ability to
have, and the outcome of a BMT. For example, prolonged
use (more than one year) of melphalan (Alkeran) can
permanently damage the stem cells in bone marrow. In
order to undergo an autologous or peripheral blood stem
cell transplant, patients must have a sufficient number
of healthy stem cells available for collection or
"harvesting" prior to the transplant.

	"Significant damage to stem cells is seen in over
50 percent of patients who have had more than a year of
therapy with melphalan or similar drugs" says Bart
Barlogie MD, University of Arkansas, Little Rock AR.

	"Patients considering an autologous BMT should
have their bone marrow or peripheral stem cells harvested
prior to initiating therapy with such drugs, or be
treated with a treatment regimen such as DEX
(dexamethasone) or VAD (dexamethasone plus vincristine
and doxorubicin) instead."

Future Investigators

	Although BMT is a promising treatment option for
multiple myeloma patients, further study is needed to
determine the optimal time to perform a BMT, the best
combination of chemotherapy to adminster pre-transplant,
the optimal source of stem cells (bone marrow versus
peripheral blood), the usefulness of purging, and what
follow-up therapy can prolong disease free-survival.
Several clinical trials are currently underway to answer
these questions.

	A recent French study found that patients who
underwent high dose chemotherapy and an autologous BMT
when first diagnosed with multiple myeloma were much more
likely to achieve a long-lasting remission of their
disease than those treated with low dose chemotherapy. A
similar study is now underway in the US.

	"While BMTs have definitely increased the number
of complete remissions and survival times in multiple
myeloma patients, further work is needed to improve upon
these results," says Bill Dalton MD, Arizona Cancer
Center, Tucson AZ. "New treatment plans to destroy
diseased cells that are currently resistant to
chemotherapy, and methods to further reduce the toxic
side effects of BMTs must be developed so that more
patients can benefit from this procedure."

BMT Newsletter (c) 1994