Understanding Stem Cell Transplant - 800-452-CURE (2873) International Myeloma Foundation 12650 Riverside Drive, Suite 206 North Hollywood, CA ...
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Understanding
Stem Cell
Transplant
International Myeloma Foundation
12650 Riverside Drive, Suite 206
North Hollywood, CA 91607 USA
Telephone:
800-452-CURE (2873)
(USA & Canada)
818-487-7455
Fax: 818-487-7454
TheIMF@myeloma.org
www.myeloma.org
03/07
Table of Contents
Introduction 5
What is Multiple Myeloma? 5
The Stages of Multiple Myeloma 6
Background Rationale for Use of High-Dose
Chemotherapy and Blood Stem Cell
Transplant or Rescue 8
Types of Stem Cell Transplant 9
How Stem Cell Transplant is Used
as a Part of Myeloma Therapy 10
What are the Benefits of High-Dose
Chemotherapy with Blood Stem Cell Rescue? 12
Practical Steps in Considering Stem Cell
Transplant as a Treatment Option 14
How Stem Cells are Collected 15
Administering High-Dose Chemotherapy 20
Preventing Infection 23
Engraftment and Recovery 24
Am I a Candidate for an
Autologous Transplant? 25
Transplants and Clinical Trials 26
Psychosocial Issues 28
Questions and Answers about Stem Cell
Transplantation 29
Questions for the Doctor 35
About the IMF 39
Glossary 42
Bibliography 47
©2007, International Myeloma Foundation, North Hollywood, California
Introduction
This booklet explains important details about
the transplant of blood stem cells. Questions
addressed include:
n What are blood stem cells?
nW
hy are blood stem cells collected and used
for transplant?
nW
hat are the benefits and risks of high-dose
chemotherapy with blood stem cell rescue as
part of the treatment for myeloma?
nW
hat is the role of high-dose chemotherapy
versus novel therapies? Can they be used in
combination?
The booklet is meant to provide you with gen-
eral information only. It is not meant to replace
the advice of your doctor, nurse, or other
healthcare practitioners. Your healthcare team
can answer specific questions related to your
personal treatment plan. All words that appear
in bold type are defined in the glossary at the
back of this booklet.
What is Multiple Myeloma?
Multiple myeloma (also known as myeloma
and plasma cell myeloma) is a cancer of the
immunoglobulin-producing plasma cells found
in the bone marrow. It is a cancer that involves
the immune system. The cancerous plasma
cells, or myeloma cells, rarely enter the blood
stream. The myeloma cells accumulate in the
bone marrow, causing the following:
nD
isruption of normal bone marrow function,
most commonly causing anemia (a low
level of red blood cells in the bloodstream),
4 5
although reduction in white blood cell and Stage II (intermediate cell mass): An inter-
platelet counts can also occur mediate stage between stage I and stage III.
nD
amage to bone surrounding accumulated Stage III (high cell mass): More
myeloma cells advanced disease. One or more of the
nR
elease of an abnormal protein, monoclonal following are present:
protein (M protein), into the blood stream n Anemia
and/or urine n A high level of calcium in the blood
nS
uppression of normal immune function, nM
ore than 3 areas of advanced lytic bone
observed as reduced levels of normal immu- lesions (destructive holes in the bones)
noglobulins and increased susceptibility to
nA
high level of M protein in the blood or
infection
urine
Myeloma cells can also grow in the form of local-
A new prognostic factor system called the
ized tumors or plasmacytomas. Plasmacytomas
International Staging System (ISS) was recently
may be single or multiple and either medullary
introduced. It is based upon the levels of two
(confined within bone marrow and bone) or
blood proteins: beta-2 microglobulin (ß2M) and
extramedullary (outside of the bone). When
albumin; the levels of these proteins predict
there are multiple plasmacytomas inside or out-
overall outcome with myeloma treatment.
side bone, this condition is also called multiple
myeloma. Stage I (best outcome)
n Serum albumin ≥ 3.5 g/dl
The Stages of Multiple Myeloma n ß2M of < 3.5 mg/l
Confronted with a diagnosis of multiple myelo-
Stage II
ma, a doctor (usually a hematologist/oncolo-
gist) must determine the stage of the disease. n Serum albumin and ß2M both < 3.5 or
Disease staging will help determine which n Serum ß2M between 3.5 and 5.5 mg/l
parts of the body have been affected and how
Stage III
severely. This will allow the doctor to decide
upon the best treatment options. n Has more elevated serum ß2M of ≥ 5.5mg/l
Stage I (low cell mass): Early disease. The Multiple myeloma is a serious cancer, but it is
bone structure appears normal or close to nor- very treatable. Many patients experience a
mal on x-ray images; the number of red blood series of responses, relapses, and remissions.
cells and amount of calcium in the blood are New treatments may extend the average sur-
normal or close to normal; and the amount of vival of 5 years or more for patients diagnosed
M protein is very low. with multiple myeloma. Patients with myeloma
can live over 10 years; some live over 20 years.
6 7
Background Rationale for Use of circulation back into the bone marrow where
they divide and grow to repopulate the
High-Dose Chemotherapy and Blood normal bone marrow space. Approximately
Stem Cell Transplant or Rescue 36–48 hours after administering the melpha-
yeloma cells and normal blood stem
nM lan, the blood and tissue levels of melphalan
cells are in the same bone marrow micro are very low and do not harm the new stem
environment. As myeloma cells build up in cell growth. This whole process of harvest
the bone marrow, they become intermixed and re-infusion at the best time is called
with normal blood stem cells responsible for “stem cell transplant.”
the production of normal red and white cells
as well as platelets. Any drugs reaching the Types of Stem Cell Transplant
bone marrow microenvironment can there- utologous stem cell transplant. Stem cells are
nA
fore damage both the myeloma cells and the harvested from a myeloma patient following
normal blood stem cells. initial therapy and re-infused after high-dose
igh-dose melphalan seriously damag-
nH melphalan therapy has been administered.
es normal stem cells. High-dose melpha- This is the most common type of stem cell
lan is a very effective treatment against transplant. The procedure can be performed
myeloma, but can also permanently damage once (single autotransplant) or twice (double
normal blood stem cells. High dosages of or tandem transplant).
melphalan can be especially helpful in eradi- yngeneic stem cell transplant. Stem cells
nS
cating myeloma cells from the bone marrow. are harvested from an identical twin. In this
To circumvent the problem of simultaneous case, the stem cells from the identical twin
severe damage to and potential destruction are infused after high-dose therapy, which
of normal blood stem cells in the bone mar- can be melphalan or other agents.
row, techniques for collecting and saving
normal blood stem cells before administering
the melphalan have been developed.
tem cells can be collected (harvested) and
nS
infused after treatment to replace those
damaged by treatment. Normal blood stem
cells are collected or “harvested” from the
patient or donor before administration of the
melphalan. The harvested normal blood stem
cells are returned to the blood circulation by
a process similar to blood transfusion. By a
seeding process, the stem cells pass from the
8 9
llogeneic stem cell transplant. Stem cells
nA n In general, stem cell transplant is a potential
are harvested from a family member who is option for all myeloma patients upon comple-
not an identical twin, but is well matched by tion of frontline therapy. However, since trans-
tissue (HLA) typing. Again, the stem cells are plant is an intensive approach, patients over
infused after the high-dose therapy. the age of 65 years and/or those with other
medical conditions may not be able to tolerate
n “Mini” or non-myeloablative allogeneic trans-
the procedure and/or may run the risk of more
plant is a newer and safer procedure than
serious complications. If stem cell transplant is
full allogenic transplant. It involves the use of
considered to be a potential option, the most
reduced intensity chemotherapy in combina-
important caution is to avoid use of melphalan
tion with an allogeneic stem cell transplant.
by mouth prior to stem cell harvesting, since this
atched Unrelated Donor (M.U.D.) stem cell
nM can lead to damage of normal bone marrow
transplant. Stem cells are harvested from a stem cells. Thus, avoiding melphalan initially
non-family member. In this case, the stem and keeping all options open is the most com-
cells are rarely a 100% tissue (HLA) match. monly recommended strategy. Conversely, if
Hence the term “mismatch” is frequently used stem cell transplant can never be an option or is
in this situation. not preferred, for whatever reason, melphalan
pills as a part of initial therapy can be a simple
How Stem Cell Transplant is Used as and very effective treatment.
a Part of Myeloma Therapy n Stem cells are harvested and transplant is
n F ollowing diagnosis, several options are performed after initial or frontline therapy.
available for initial or front-line therapy. This means that treatment is used to achieve
Typical frontline regimens currently response and at least some degree of remis-
utilized are: sion before proceeding to therapy with high-
• Thalidomide plus dexamethasone dose melphalan and blood stem cell rescue.
• Dexamethasone alone
•V
arious dexamethasone combinations
incorporating an anthracycline (e.g.,
Adriamycin® or Doxil® as part of VAD or
VDD), Velcade®, or more recently Revlimid®
combinations. Cytoxan® can also be used
as part of the initial approach.
Full details of these treatments are discussed in
other publications of the International Myeloma
Foundation.
10 11
Major details include: dose therapy for a patient who has already
• Initial therapy for 3–6 months with drugs achieved VGPR or CR is under investigation.
that do not damage normal blood stem n Enhanced response without the necessity
cells. of maintenance. A particular benefit of high-
• Ideally, response is achieved with > 50% dose therapy is that added response can
reduction in myeloma protein levels and/or occur within a few weeks of the procedure. If
other indicators of active myeloma prior to CR or VGPR occur, then such patients can be
the collection of normal blood stem cells. followed and monitored without the absolute
However, even lesser degrees of response need for ongoing maintenance anti-myeloma
may be sufficient to allow safe and effective therapy. Patients undergoing high-dose therapy
stem cell collection to be performed. also tend to be in remission longer and thus
to have a longer period before retreatment is
What are the Benefits of required. Thus, the potential ongoing toxicity,
High-Dose Chemotherapy with Blood inconvenience, and expense of maintenance
Stem Cell Rescue? can be avoided. However, depending upon
the individual details, including chromosome
n Further improvement in the level of response testing, maintenance therapy and/or other
achieved with frontline therapy is a major (consolidation) therapy may be recommended
advantage of high-dose therapy with stem cell after transplant.
transplant. Over half the time, partial responses
will be improved to either VGPR (very good n Potential benefit with double or tandem trans-
partial response, with ≥ 90% myeloma protein plantation. If CR or ≥ VGPR are not achieved
reduction) or CR (complete response, with dis- with a single autologous transplant, then a
appearance of measurable myeloma protein second autologous (or an alternate transplant
level). such as “mini allogeneic” [see above]) can be
offered. Continuing in the attempt to achieve
n Enhanced benefit in patients who have ≥ VGPR with the second transplant does appear
already achieved VGPR or CR. With the advent to confer benefit.
of more frequent VGPR or CR with novel front-
line therapies, the added benefit of high-dose n Significance of achieving CR or VGPR. It has
therapy in this setting is coming under closer been generally accepted that patients achiev-
scrutiny. High-dose chemotherapy has con- ing better response such as CR or VGPR have
ferred statistically significant benefit following better outcomes (versus, for example, partial
traditional chemotherapy induction using, for response [PR]). However, further studies are
example, VAD chemotherapy. However, novel required. Having a durable response at a par-
therapy combinations can produce high levels ticular level, whether that is a simple PR ( ≥ 50%
of VGPR and CR. The additional benefit of high- improvement), VGPR (≥ 90%) or CR (100%), is
12 13more important than the level of the response STEP FOUR
in itself. Response lasting ≥ 2 years is particu- eview with the physician the pros and cons
nR
larly beneficial. The relative benefit of stable of stem cell transplant (and/or stem harvest-
disease at the PR, VGPR, or CR level is under ing without immediate transplant).
further study.
n If ≥ 50% response (PR: ≥ 50% reduction in
Practical Steps in Considering Stem myeloma protein level in blood and/or
urine) is achieved, stem cell harvesting can
Cell Transplant as a Treatment Option be planned if it is agreed to proceed. If there
STEP ONE is no plan for harvest and/or transplant, a
onfirm the diagnosis of active myeloma that
nC plan for ongoing maintenance or follow-up
requires anti-myeloma treatment. treatment is required.
n If there isundergo as many as 50–100 bone marrow or 5th day after starting the injections. The col-
aspirations from the back of the pelvic bone to lections and injections will continue daily until
remove enough bone marrow and stem cells sufficient stem cells are obtained.
to use for future transplant. This was obviously
2. Using chemotherapy plus growth factors.
painful, frightening, and inconvenient. The dis-
Chemotherapy with growth factors may also be
covery that stem cells could be collected from
used to release stem cells from the bone marrow
the bloodstream by giving a patient or donor
into the bloodstream. The doctor will explain
injections of stem cell growth factors such as
why it may or may not be appropriate to use
Neupogen®, Neulasta®, or Leukine® to trigger
chemotherapy in addition to growth factors.
the release of bone marrow stem cells into the
The doctor will explain the chemotherapy that
bloodstream was a major breakthrough. With
will be administered to mobilize the blood stem
refinements over the years, this has become the
cells and its potential benefits and side effects.
standard method. It is rarely necessary to use
Following chemotherapy for stem cell mobiliza-
the old method of direct bone marrow harvest-
tion, a white cell growth factor is given by injec-
ing from the pelvic bone.
tion under the skin daily for approximately ten
Methods of Collecting Stem Cells from the days. This procedure is therefore longer and
Blood Stream (Peripheral Blood Stem Cells much more intensive than using growth factors
[PBSC]) alone. The patient or someone who agrees to
There are two main methods for collecting be responsible may be taught how to give the
stem cells: 1) giving growth factors alone or growth factor injection so that it can be admin-
2) giving growth factors with chemotherapy. istered at home. Some patients may receive
their injections at the clinic/hospital or from
1. Growth factors alone.
visiting nurses. Once the number of stem cells
Growth factors are drugs that stimulate blood
in the blood stream is high enough, they will be
stem cells both to grow and to be released
collected over 2–5 days, while the patient is still
into the blood stream. There are red cell and
receiving the growth factor injections.
white cell growth factors. These medications
are administered subcutaneously (under the
skin). Growth factors are often used for patients
receiving chemotherapy to hasten their white
and red cell count recovery. The white cell
growth factors (Neupogen, Neulasta, Leukine)
used in high doses stimulate the release of stem
cells from the bone marrow into the blood-
stream. This process is called “mobilization.”
The injections are given daily for three or more
days. Stem cells are usually collected on the 4th
16 17The Collection or Harvesting Procedure The most common side effects experienced dur-
In medical language, the harvesting is called ing apheresis are slight dizziness and tingling
apheresis or leukapheresis – literally the sensations in the hands and feet. Less common
removal of white cells from the blood stream. side effects include chills, tremors, and muscle
Apherisis is a procedure whereby blood from cramps. These side effects are temporary and
the patient or donor passes through a special are caused by changes in the volume of the
machine that separates (using a centrifuge patient’s blood as it circulates in and out of
technique) and then removes stem cells. The the apheresis machine, as well as by blood
rest of the blood is immediately returned to the thinners added to keep the blood from clotting
patient or donor. Compared to direct bone mar- during apheresis.
row harvesting, this is a remarkably simple and
Processing stem cells: After collection, the periph-
pain-free procedure.
eral blood (or occasionally direct bone marrow
Apheresis/Leukapheresis: Prior to the start of material) is taken to the processing laboratory,
apheresis, a thin flexible plastic tube called a which is usually located within the hospital or
catheter is inserted through the skin and into a local blood bank. In the processing laboratory,
vein so that blood can be taken out. The cath- the bone marrow or blood cells are prepared
eter is usually inserted into the chest just below for freezing (cryopreservation). The stem cells
the collarbone. Insertion of the catheter is usu- are mixed with a solution containing the chemi-
ally done as an outpatient procedure, and only cal DMSO (dimethyl sulfoxide) to prepare the
a local anesthetic is necessary. The site where stem cells for freezing. The stem cells are then
the catheter enters the skin may be sore for a frozen and stored in liquid nitrogen. The stem
few days; the discomfort may be relieved with cells will be frozen until the time they will be
medications like acetaminophen (Tylenol®). The needed for the transplant. They can be stored
catheter may be kept in place for several weeks frozen for as long as necessary. There is some
because it can be used to give chemotherapy deterioration with time, but excellent function of
after stem cells have been collected. Sometimes stem cells is retained for at least 10 years.
the same catheter is used during the transplant
procedure as well. During this procedure, How many stem cells do I need? Over the years,
blood is collected through the catheter and a number of studies have been completed to
processed through a blood-processing machine determine the number of stem cells you need to
to remove the stem cells. The rest of the blood safely undergo high-dose therapy. The number
is returned through part of the same catheter of stem cells is quantified by a special labora-
(the lumen not being used in a double lumen tory technique called “CD34+ cell analysis by
catheter) or by using a different catheter. The flow cytometry.” A small sample of the stem cell
apheresis procedure will last 3–4 hours each collection is tested for the number of CD34+
day for 1 to 5 days. Apheresis is usually done cells in the product. We know that a minimum
as an outpatient procedure. number of stem cells to safely complete a trans-
18 19plant is 2 million CD34+ cells per kilogram chemotherapy is to kill myeloma cells inside
of body weight. The number of CD34+ cells the patient’s body. The most common type of
is checked in each daily collection and the high-dose chemotherapy used to treat myeloma
number tallied. The stem cell collection process is melphalan administered at a dose of 200
continues daily until the planned number of milligrams per square meter (mg/m2) of body
stem cells is collected – usually 1–4 days. Some surface area (size of patient). Depending on
transplant centers check the number of CD34+ the type of myeloma and other factors, some
cells BEFORE starting leukapheresis to make patients may receive a second transplant 3 to
certain there will be a good collection that day. 6 months after the first transplant (double or
Most transplant physicians collect enough stem tandem transplant). A patient should discuss
cells for two transplants (over 4 million CD34+ with the doctor the pros and cons of more than
cells per kilogram body weight). In situations one transplant planned and performed back-
where a sufficient number of blood stem cells to-back versus the possibility that the cells will
cannot be harvested, patients may qualify for be stored for a potential second transplant at
a compassionate use program of AMD-3100 a later time.
(Mozobil®), an experimental drug that boosts
Autologous Stem Cell Transplant or
stem cell production.
Infusion
Administering High-Dose Since high-dose treatment destroys the normal
bone marrow in addition to the myeloma cells,
Chemotherapy
the blood stem cells must be given back to
After the stem cells are frozen and stored, the restore the bone marrow. The previously collect-
patient is ready to receive high-dose chemo- ed stem cells will be unfrozen and given back,
therapy. This treatment is designed to destroy through a catheter, into the bloodstream (as
myeloma cells more effectively than standard- one would receive a blood transfusion) one to
dose chemotherapy. The purpose of high-dose two days after administration of the high-dose
chemotherapy. This procedure is often referred
to as the transplant. The transplant takes place
in the patient’s room: it is not a surgical pro-
cedure. The frozen bags of bone marrow or
blood cells are thawed in a warm water bath,
and then injected into the bloodstream through
the catheter. Upon thawing, the DMSO (freez-
ing agent) evaporates into the air and creates
a distinct and somewhat unpleasant garlic
smell. Most centers infuse one bag at a time. It
usually takes 1–4 hours for the infusion. Infused
20 21stem cells travel through the bloodstream, and Preventing Infection
eventually, to the bone marrow, where they
begin to produce new white blood cells, red During the first 2–3 weeks after transplantation,
the re-infused stem cells migrate to the bone
blood cells, and platelets. It takes 10–14 days
marrow and begin the process of producing
for the newly produced blood cells to enter the
replacement blood cells, a process called
bloodstream in substantial numbers. Growth
engraftment. Until engraftment of the stem cells
factors may again be given to the patient to
takes place, patients are very susceptible to
speed up this process.
developing infections. Even a minor infection
In addition to obliterating the bone marrow, like the common cold can lead to serious prob-
high-dose chemotherapy can cause other lems because the body’s immune system is so
severe side effects, which may require that weakened by the effects of the high-dose che-
some patients be admitted to the hospital for motherapy. Therefore, special precautions are
treatment during this period. (Not all transplant necessary during recovery. Since the patient’s
centers require that patients remain in the immune system is very weak, patients may
hospital after the infusion of stem cells; some remain in the hospital until the white blood cell
have facilities close by where patients may stay counts reach a level safe enough for the patient
and be monitored daily at the hospital on an to be discharged.
out-patient basis, while others allow patients To prevent infection, the following supportive
who live close to the hospital to sleep at home care measures may be required:
and be monitored at the hospital). The average
•A
ntibiotics are often prescribed to help pre-
time in the hospital (or a nearby facility) for
vent infection.
the chemotherapy, transplant, and recovery is
approximately 3 weeks. Shortly before starting •V
isitors should wash their hands and may be
chemotherapy, patients usually are given large asked to wear masks and rubber gloves to
amounts of fluid to prevent dehydration and protect the patient.
kidney damage from the chemotherapy. Some • F resh fruits, vegetables, and flowers may be
of the more common side effects of chemother- prohibited from the patient’s room as these
apy include nausea, vomiting, diarrhea, mouth can carry infection (bacteria and fungi).
sores, skin rashes, hair loss, fever or chills, and • If infection and/or fever occurs (as the result
infection. Medications designed to prevent or of lowered white cell counts), the patient may
lessen some of the expected side effects of be admitted to the hospital and be given
treatment are given routinely. Patients are very intravenous antibiotics.
closely monitored during and after the adminis-
tration of high-dose chemotherapy. Monitoring Engraftment and Recovery
includes daily weight measurement as well as Once the stem cells have been re-infused, it
frequent measurements of blood pressure, heart will take about two weeks for blood counts to
rate, and temperature.
22 23recover. Many transplant centers will again use Am I a Candidate for an Autologous
white blood cell growth factors (Neupogen,
Neulasta, Leukine) after the transplant to help
Transplant?
stimulate the bone marrow to produce normal A stem cell transplant is a treatment option for
blood cells. These injections (under the skin) will many myeloma patients; however, it is not a
continue until the white blood count returns to cure. It can improve the duration of remission
normal. During this time, red blood cell and/or and survival. It can also provide a better qual-
platelet transfusions may be necessary. ity of life for most patients. Not all patients
with myeloma are candidates for a stem cell
Waiting for the transplanted stem cells to
transplant. Many factors must be taken into
engraft, for blood counts to return to safe levels,
consideration. These include factors related to
and for side effects to disappear is often the
the myeloma itself and patient-related factors.
most difficult time for both the patient and his
or her family and friends. During this period Myeloma-Related Factors
patients will feel weak and very fatigued. • type of myeloma
Having a support network is very important • disease stage
during this period. Recovery can be like a roller
• disease aggressiveness
coaster ride: one day a patient may feel much
• responsiveness to treatment
better, only to awake the next day feeling as
sick as ever. It is important during this period to • serum albumin
take things one day at a time. Once new blood • beta-2 microglobulin
cells are being made, symptoms will resolve, the • chromosome analysis
risk of serious infections will be reduced, and
Patient-Related Factors
transfusions will no longer be needed.
• age
After being discharged from the hospital, a • health status
patient continues recovery at home for two to • kidney, heart, lung, and liver function
four months. Although patients may be well
• patient preference
enough to leave the hospital, their recovery
will be far from over. For the first several weeks We cannot stress enough that myeloma is a
the patient may be too weak to do much more highly individualized disease. While there are
than sleep, sit up, and walk a little around the similarities between patients, each case has its
house. Frequent visits to the hospital will be own distinct characteristics. There will be testing
required to monitor progress. Patients usually to determine how much myeloma there is in
cannot resume normal activities or return to full- your body and how aggressive it is. All of these
time work for up to three to six months after the variables will be weighed before determining
transplant, although this varies from individual whether a transplant is appropriate for you.
to individual. Therefore, general statements regarding patient
24 25outcomes both during the transplant procedure by infusion of the other half of the stored stem
and post transplant are inappropriate. cells. Preliminary data indicates that tandem
transplants result in improved disease control
When to transplant is also an important con-
and survival in patients who do not achieve
sideration. Most transplant physicians believe
either VGPR or CR following first autologous
it is better to perform the transplant early in the
transplant.
disease course. However, there is no absolute
clinical data to suggest that transplantation Radiopharmaceuticals (radioactive bone-target-
earlier in the treatment regimen is better than ed therapy) are combined with high-dose che-
waiting until later. Remember, in most cases, motherapy and autologous stem cell transplant
unlike a heart attack, myeloma gives the patient as a means to increase response rates. This
the luxury of time to do some homework and approach allows for a two-pronged attack on
to gather the information needed to make an the myeloma through high-dose chemotherapy
informed decision about what’s right for him plus a radioactive compound that only attacks
or her. For example, one could have stem cells the bone marrow. There is currently a radio-
harvested and saved for a later treatment. This pharmaceutical agent in myeloma clinical trials:
leaves the patient open to other more imme- Quadramet (samarium Sm-153 lexidronam).
diate treatment options. These are things to
A “mini” (non-myeloablative) allogeneic trans-
discuss with the doctor. It’s important to remem-
plant involves the use of mild therapy (chemo-
ber that even if someone is a good transplant
therapy and/or radiation therapy) to suppress
candidate, the ultimate decision about whether
the patient’s immune system to allow for donor
or not to have a transplant is the patient’s.
stem cells to grow. This dose of chemotherapy
does not destroy the bone marrow but does
Transplants and Clinical Trials
allow for the donor’s blood cells and immune
A single autologous stem cell transplant is system to grow. After the lowered dose of
currently considered the standard of care for chemotherapy is administered, the patient
patients with multiple myeloma. However, there receives the donor’s stem cells. Once the allo-
are a number of novel approaches that are geneic stem cells grow, the donor’s immune cells
being evaluated to try to improve patient out- attack the myeloma. This is a form of immunother-
comes. These are being conducted as clinical apy. The risk of this procedure is that the donor’s
trials. These include the following: immune system will “overreact” and attack more
A tandem autologous transplant is an approach than the myeloma cells. This reaction is called
that utilizes two autologous transplants. “graft-versus-host disease,” which can be very
Sufficient stem cells are collected prior to the serious and potentially life threatening.
first transplant. Three to six months after the Sequential autologous transplant followed by
first transplant, the patient receives a second a mini allogeneic transplant. Pilot studies using
similar course of high-dose therapy followed sequential transplants have shown promise.
26 27This involves high-dose chemotherapy with an Questions and Answers
autologous transplant to destroy the majority of
the myeloma cells, followed 2 to 4 months later
about Stem Cell Transplantation
by an allogeneic mini-transplant to allow the Listed below are some of the questions frequent-
donor’s immune cells to destroy any remaining ly asked by people with myeloma who have
myeloma cells. As with a single mini allogeneic had or are considering a stem cell transplant.
transplant, there is a risk of graft-versus-host dis- These questions and other concerns should be
ease, which can be very serious and potentially discussed with the doctor and members of the
life threatening. healthcare team before making any final deci-
sions about the patient’s treatment plan.
Maintenance therapy is an approach that
involves lowered doses of anti-myeloma drugs Q. Why is a stem cell transplant necessary for
to maintain longer remission and survival after a multiple myeloma patient?
a transplant. Currently, some of the drugs A. The transplant procedure allows the patient to
being evaluated include thalidomide, Revlimid, receive high doses of chemotherapy to kill more
prednisone, and dexamethasone, alone or in myeloma cells. This therapy is so potent that it
combinations. destroys all of the bone marrow. Without bone
marrow, the body is unable to manufacture
Psychosocial Issues blood cells needed to carry oxygen, help blood
High-dose chemotherapy and autologous clot, and defend against infection. Therefore,
transplantation can place an enormous stress a stem cell transplant replaces the destroyed
on patients and families. Physical, psycho- marrow, rescuing the patient from the effects of
logical, emotional, and financial stresses can high-dose chemotherapy.
be overwhelming. Patients and families may Q. Am I a candidate for bone marrow or
experience feelings of anger, depression, and peripheral blood stem cell transplant?
anxiety over an unknown future and a lack A. Medical experts have yet to arrive at a set of
of control. Support services offered through fixed guidelines for selecting patients who will
the hospital and many other organizations, benefit the most from a transplant. Increasingly
including myeloma support groups, are very accepted as a part of multiple myeloma
important during this time. We urge you to treatment protocols, successful transplantation is
take advantage of these services, or to seek a a function of the patient’s age, general physical
referral from your oncologist for psychological condition, stage of disease, and responsiveness
counseling and/or a psychiatric consultation. to prior treatments. Only the patient’s physician
can provide a patient with the best assessment
of his or her chances for long-term survival.
28 29Q. Does taking alkylating agents such as nurses, and other members of the multiple
melphalan, busulfan, and cyclophospha- myeloma treatment team – and learn more
mide (Cytoxan) reduce my suitability for a about how they approach a transplant. See
transplant? the room where your transplant will occur and
A. Alkylating agents are one of the most effec- where you’ll be spending your recuperation
tive ways of killing myeloma cells inside the time. Find out what part of your procedure will
body. However, their prolonged use – more be performed in a clinic or a doctor’s office
than 4 to 6 months – will reduce the ability to and what part will be done in the hospital. You
easily harvest a patient’s stem cells. Therefore, should be comfortable with the center before
when considering a transplant, a patient should you begin your transplant.
first discuss the total treatment plan to ensure Q. If my doctor agrees that a stem cell trans-
that there are as many short-term and long- plant is an appropriate treatment for my dis-
term treatment options available as possible. ease, what can I do now to prepare for the
It should be emphasized, however, that collec- experience?
tion should ideally be done before using any
A. The patient can do a lot to get ready for
alkylating agents.
the transplant. By reading this brochure, a
Q. How do I select a transplant center? patient has already taken the most important
A. A transplant is a complicated medical step: learning as much as possible about the
procedure that requires an expert team of procedure. A patient should speak with the
doctors, nurses, social workers, psychologists, doctor, seek out fellow survivors, and read as
and allied health professionals who understand much as possible, including the publications
the procedure, have performed it success- and newsletters from the International Myeloma
fully many times, and are equipped to respond Foundation. Patients should ask questions about
when medical and emotional problems arise. what they’ve learned and strive to read all the
Today, medical centers that meet these criteria newest information coming from research. We
can be found throughout the country. Many suggest that patients bring a tape recorder or
of these centers specialize in treating patients a friend along to the doctor’s office so that they
with many different types of cancer. To find the can give full attention to the doctor. Patients
one best suited for patients with multiple myelo- should share what they know with family and
ma, you should talk with your doctor, other loved ones so that they will know what to
multiple myeloma patients, and the International expect – and how they can help in the weeks
Myeloma Foundation. and months ahead.
Q. What goes on at a transplant center? The doctor will perform a series of tests to
A. To understand what goes on at a transplant confirm that the patient is well enough to toler-
center, we strongly suggest a visit to one or ate the transplant. All the data gathered on
more centers. Meet with the staff – doctors, the performance of the heart, lungs, kidneys,
30 31and other vital organs will enable the doctor to riskier than most. Nonetheless, medical studies
compare the patient’s health before and after have shown that over 95% of patients (usually
the procedure. In most cases, the patient won’t closer to 99%) survive transplant.
have to be hospitalized for these tests since they
can be performed in the doctor’s office. Q. Can the patient relapse after a transplant?
A. Yes. Unfortunately, the majority (at least 50%)
Q. What side effects should I anticipate from of all multiple myeloma patients relapse 18 to
the transplant? 36 months after their transplant is completed.
A. Side effects can be expected from every
type of medical treatment, even the use of Q. I’ve heard a lot about myeloma purging.
aspirin. Each patient reacts differently to che- Can it help?
motherapy and other drugs given during the A. The process of purging removes myeloma
transplant. No two patients share exactly the cells from peripheral blood taken from the
same side effect profile. patient’s body prior to transplant. High-dose
chemotherapy is used to kill myeloma cells
Patients should therefore seek a transplant that are within the body. Stem cell selection,
center where the doctors, nurses, and allied or “purging,” is used to remove myeloma cells
health professionals have performed a number from the collected stem cells prior to the trans-
of transplants and appear competent to care plant. The goal of this strategy is to reduce the
for each individual myeloma patient’s needs. number of myeloma cells both within the
patient’s body as well as in the peripheral
Q. What happens during re-infusion?
blood that will be re-infused into the patient.
A. After chemotherapy the patient receives a
Recent evidence indicates that this technology
re-infusion of his or her own stem cells. The
is not effective in myeloma. Therefore, very
stem cells will be thawed and infused into the
few centers currently use stem cell purging for
patient’s catheter either through a syringe or
myeloma patients.
from an intravenous infusion bag. While the
re-infusion takes place the patient may feel Q. How long will the transplant patient stay in
warm or lightheaded. The chemical used to the hospital?
keep the stem cells fresh has a garlic smell that A. Patients stay in the hospital for about 2 to 3
the patient might be able to taste. The oncolo- weeks. The length of stay varies from patient to
gist may re-prescribe or adjust the patient’s patient. Some patients may have several short
medication to make him or her feel more com- admissions.
fortable during this procedure.
Q. When will the stem cells start to grow
Q. Can a patient die from the transplant itself? again?
A. Every medical procedure carries risk, and A. Stem cells start to grow back or “engraft”
a transplant for multiple myeloma patients is within 10–14 days after re-infusion.
32 33Q. What will the patient’s quality of life be after of their treatment program. Because all drugs,
transplant? synthetic and natural, interact, and may cre-
A. On average, patients take 3 to 6 months ate unanticipated side effects, patients should
to recover from a transplant. By this time, the always consult their doctors about their use.
immune system will once again fight infections The doctor should be informed of the names
because the bone marrow is producing healthy of all the alternative and complementary thera-
blood cells. Hair will grow back, but the taste pies being taken so that he or she can adjust
buds might still be a little quirky. Foods that the regimen accordingly. It is important to note
tasted good before a transplant might not taste that even seemingly innocuous over-the counter
good now. However, in most cases, patients drugs, e.g., ibuprofen, may be harmful to a
should be able to return to normal daily activi- myeloma patient.
ties. It can take as long as a year to recover
normal functioning. Patients and their caregiv- Questions for the Doctor
ers must take one day at a time. There will These are questions we suggest be discussed
be bad days and good days, and they won’t with the doctor to provide better understanding
necessarily come in that order. Patients should of the transplant procedure and its effects on
prepare themselves to feel differently each day the patient’s life. Space is provided for notes:
during the recovery process.
“Am I a candidate for stem cell transplant?”
Q. Should transplant patients expect changes in
________________________________________
their emotions?
A. Yes. Transplant is more than just a medical ________________________________________
procedure. Because it forces the patient to “What does high-dose chemotherapy with trans-
rely upon the oncologist and other members plant hope to achieve that can’t be achieved by
of the transplant team, as well as on family standard chemotherapy?”
and friends, there is often a loss of the sense
of independence and control. Feelings of iso- ________________________________________
lation, depression, and helplessness are com- ________________________________________
mon to transplant patients. Patients and loved
ones should seek assistance from a trained ________________________________________
professional who has experience in counsel- “What treatment protocols are there at your
ing. Help may also be found through patient institution and how do you decide which one is
support groups. right for me?”
Q. What alternative and complementary thera- ________________________________________
pies can be taken during and after transplant?
________________________________________
A. Some patients believe that alternative and
complementary therapies are an important part ________________________________________
34 35“Does taking alkylating agents such as melpha- “Will you be the doctor who provides my
lan, busulfan, and Cytoxan reduce my suitability ongoing care?”
for a transplant?”
________________________________________
________________________________________
________________________________________
________________________________________
________________________________________
________________________________________
“What goes on at a transplant center?”
“How do I select a transplant center?”
________________________________________
________________________________________
________________________________________
________________________________________
________________________________________
________________________________________
“If we decide that transplant is an appropriate
“How many transplants has this center treatment for my disease, what can I do now to
performed for multiple myeloma and what are prepare for the procedure?”
the success rates?”
________________________________________
________________________________________
________________________________________
________________________________________
________________________________________
________________________________________
“When does the transplant procedure begin?”
“How long do patients transplanted in your cen-
________________________________________
ter live after the transplant itself? How does this
compare with national averages?” ________________________________________
________________________________________ “What drugs will be prescribed for use before,
during, and after the transplant? What do they
________________________________________
do and what are their side effects?”
________________________________________
________________________________________
“Will you be the doctor who performs the trans-
________________________________________
plant and who are the other members of the
team?” ________________________________________
________________________________________ “How long is the entire treatment cycle, from
preparation for the transplant to recovery?”
________________________________________
________________________________________
________________________________________
________________________________________
36 37“How long will I have to be in the hospital? How About the IMF
often are my follow-up visits going to be?”
“One person can make a difference,
________________________________________
Two can make a miracle.”
________________________________________
Brian D. Novis
________________________________________ IMF Founder
“How will the transplant procedure affect my Myeloma is a little-known, complex, and often
ability to function? How can I expect to feel dur- misdiagnosed bone marrow cancer that attacks
ing and after the transplant?” and destroys bone. Myeloma affects approxi-
mately 75,000 to 100,000 people in the
________________________________________
United States, with more than 19,000 new
________________________________________ cases diagnosed each year. Although there
is presently no known cure for myeloma, doc-
________________________________________
tors have many approaches to help myeloma
________________________________________ patients live better and longer.
“What side effects of my transplant should I The International Myeloma Foundation (IMF)
anticipate?” was founded in 1990 by Brian and Susie
Novis shortly after Brian’s myeloma diagnosis
________________________________________
at the age of 33. It was Brian’s dream that
________________________________________ future patients would have easy access to
medical information and emotional support
________________________________________
throughout their battle with myeloma. He estab-
________________________________________ lished the IMF with the three goals of treatment,
“What are the risks of the transplant procedure? education, and research. He sought to provide
Is there a high survival rate for high-dose therapy a broad spectrum of services for patients and,
with stem cell transplant? their families, friends, and health- care provid-
ers. Although Brian died four years after his
________________________________________ initial diagnosis, his dream did not. Today, the
________________________________________ IMF reaches out to an international membership
of more than 145,000. The IMF was the first
________________________________________ organization dedicated solely to myeloma, and
________________________________________ today it remains the largest.
The IMF provides programs and services to aid
in the research, diagnosis, treatment, and man-
agement of myeloma. The IMF ensures that no
one must brave the myeloma battle alone.
38 39We care for patients today, while working SUPPORT
toward tomorrow’s cure. Myeloma Hotline: 800-452-CURE (2873)
Toll-free throughout the United States and
How Can the IMF Help You? Canada, the IMF Hotline is staffed by trained
information specialists and is in frequent
PATIENT EDUCATION
interaction with members of our Scientific
Information Package
Advisory Board.
Our free IMF InfoPack™ provides comprehensive
information about myeloma, treatment options, Support Groups
disease management, and IMF services. It A worldwide network of more than 100
includes our acclaimed Patient Handbook. myeloma support groups hold regular meetings
for members of the myeloma community. The
Internet Access
IMF conducts annual retreats for leaders of
Log on to www.myeloma.org for 24-hour myeloma support group leaders.
access to information about myeloma, the IMF,
education, and support programs. RESEARCH
Online Myeloma Forum BANK ON A CURE®
Join the IMF Internet Discussion Group at This DNA bank will provides genetic data
www.myeloma.org/listserve.html to share your research in new drug development.
thoughts and experiences. The International Staging System (ISS)
Myeloma Minute ™ This updated staging system for myeloma
Subscribe to this free weekly email news- enhances physicians’ ability to select the most
letter for up-to-the-minute information about appropriate treatment for each patient.
myeloma. Research Grants
IMF Patient & Family Seminars™ Leading the world in collaborative research
Meet with leading experts in myeloma treat- and achieving extraordinary results, the IMF
ment to learn more about recent advances in Grant Program supports both junior and senior
therapy and research. researchers working on a broad spectrum of
projects. The IMF has attracted many young
Myeloma Matrix™
investigators into the field of myeloma; they
On our website and in print, this document is a
have remained in the field and are actively
comprehensive guide to drugs in development
pursuing a cure for this disease.
for myeloma.
Myeloma Today™ Newsletter
Our quarterly newsletter is available free of
charge by subscription.
40 41Glossary Autologous (autograft) stem cell transplantation: Refers to
stem cells that are collected from the patient and are
Alkylating agent: A chemotherapeutic agent such as given back to the same patient after he or she receives
melphalan (Alkeran) or cyclophosphamide (Cytoxan). high-dose chemotherapy. Most stem cell transplants in
Alkylating refers to the way in which these agents cross- myeloma are autologous transplants.
link the DNA of myeloma cells and block cell division.
Beta-2 microglobulin: A small protein found in the blood.
Allogeneic (allograft) stem cell transplant: Refers to stem cells High levels occur in patients with active myeloma. Low or
that are taken from a donor and given to the patient. normal levels occur in patients with early myeloma and/
Most allogeneic stem cell transplants are performed or inactive disease. Approximately 10% of patients have
using donor peripheral blood stem cells. Conventional myeloma that does not produce beta-2 microglobulin.
allogeneic transplants for myeloma patients are rarely For these patients, beta-2 microglobulin testing cannot
performed in the US due to excessive risk to the patient. be used to monitor the disease. At the time of relapse,
A newer and, for myeloma, safer technique (discussed beta-2 microglobulin can increase before there is any
below) is a non-myeloablative or “mini-transplant” that is change in the myeloma protein level. Therefore, 90%
currently being evaluated in clinical trials. To determine of the time, beta-2 testing is very useful for determining
if a patient has a potential donor match, a special blood disease activity.
test call HLA testing is done. A donor may be a family
Blood stem cells: Stem cells, derived from the blood, that
member or may be obtained through a donor registry
result in faster hematologic recovery.
such as the National Marrow Donor Program (NMDP).
Rarely, donor cells may be obtained from an umbilical Bone marrow aspiration: The removal, by needle, of a
cord blood bank. sample of tissue from the bone marrow.
Anemia: A decrease in the normal number of red blood Bone marrow transplant: Obtained from the bone marrow
cells, usually below 10 g/dl with over 13–14 g/dl being of the patient or the donor. Very few bone marrow trans-
normal. Myeloma in the bone marrow blocks red cell plants are currently performed due to the availability of
production, thus causing anemia, the symptoms of which peripheral blood stem cells. Rarely, bone marrow may
are shortness of breath, weakness, and tiredness. be collected for patients who are unable to collect suf-
ficient number of stem cells from the peripheral blood.
Apheresis/Leukapheresis: Sometimes called leukapheresis,
apheresis is a procedure in which blood is taken from a CD34+: This is the laboratory marker used to single out
patient or donor and the portion of the blood containing and quantify the number of stem cells in your blood
plasma, white blood cells, and platelets is separated. stream. There is a certain minimum number of CD34+
Red blood cells are transfused back into the donor. The stem cells that are required to safely support a transplant
portion containing white blood cells contains the rare procedure.
stem cells.
Chemotherapy: Drugs that are used to kill cancer cells.
Autologous peripheral blood transplantation: (see Autologous
Creatinine: A small chemical compound normally excret-
Stem Cell Transplantation) A procedure in which a
ed by the kidney. If the kidneys are damaged, the serum
patient’s blood is collected by apheresis, stored, and
level of creatinine builds up, resulting in elevated serum
re-infused following high-dose chemotherapy. creatinine. The serum creatinine test is used to measure
kidney function.
42 43Colony-stimulating factor (CSF): Proteins that stimulate the Monoclonal protein (M protein): An abnormal protein pro-
development and growth of blood cells. Neupogen, duced by myeloma cells which accumulates in and dam-
Neulasta, and Leukine are colony stimulating factors ages bone marrow. A high level of M-protein indicates
that are used to mobilize stem cells from the bone mar- that myeloma cells are present in large numbers.
row into the bloodstream prior to apheresis. These may
also be used after the transplant to hasten blood count Myeloablation: The killing of bone marrow by radiation or
recovery. chemotherapy. This term usually refers to the complete or
near-complete destruction of the bone marrow.
Complete response (CR): CR is the absence of myeloma
protein from the serum and/or urine by standard testing; Multiple myeloma: A cancer arising from the plasma cells
absence of myeloma cells from the bone marrow and/ in the bone marrow. The plasma cells in patients with
or other areas of myeloma involvement; clinical remis- multiple myeloma form abnormal antibodies, possibly
sion and improvement of other laboratory parameters to damaging the bone, bone marrow, and other organs.
normal. CR is not the same thing as a cure. Peripheral blood stem cell (PBSC): Stem cells collected from
Engraftment: The process by which stem cells in the trans- the blood. These cells are similar to stem cells found in
planted bone marrow or peripheral blood migrate to the the bone marrow. The term “peripheral” means that the
patient’s bone marrow and begin to grow and produce cells come from blood outside of the marrow.
new white blood cells, red blood cells, and platelets. Peripheral blood stem cell (PBSC) transplant: Obtained from
Growth factors: Drugs that stimulate blood stem cells both the patient or donor bloodstream. Using PBSC for trans-
to grow and to be released into the bloodstream. plantation allows for easier and safer collection of stem
cells and faster recovery after the transplant than bone
Immune system: The function of a number of related body marrow transplant.
organs that protect the body from disease organisms,
other foreign bodies, and cancers. Plasma cell: A type of white blood cell that produces
antibodies.
Immunoglobulin: A protein produced by plasma cells (a
type of white blood cell) which helps fight infection. Also Plasmacytoma: A tumor made up of cancerous plasma
known as an antibody. cells.
International Staging System (ISS): the most current stag- Platelets: Granule-containing cellular fragments critical
ing system for myeloma, the ISS is the result of the for blood clotting and sealing of wounds. Platelets also
collaboration of more than twenty research institutions contribute to the immune response.
world-wide. Red blood cell: A blood cell that carries oxygen from the
Lytic bone lesions: Holes in the bone. lungs throughout the body.
M protein (M spike): Antibodies or parts of antibodies Remission or response: Remission and response are used
found in unusually large amounts in the blood or urine interchangeably. Complete Remission (CR) is the com-
of myeloma patients. M spike refers to the sharp pattern mon abbreviation for both. CR is defined as the absence
that occurs on protein electrophoresis when an M protein of myeloma protein from serum and/or urine by stan-
is present. Synonymous with monoclonal protein and dard testing, absence of myeloma cells from the bone
myeloma protein. marrow and/or other areas of myeloma involvement,
clinical remission, and improvement of other laboratory
parameters to normal.
44 45You can also read
