What is a stem cell transplant

A blood stem cell transplant is a medical procedure used to treat people with a variety of life-threatening diseases. The technical name for a blood stem cell transplant is a hematopoietic stem cell transplant. Hematopoietic means blood-forming.

You may also hear the hematopoietic stem cell transplant procedure referred to as a:

• bone marrow transplant
• stem cell transplant (or peripheral blood stem cell transplant)
• cord blood transplant

To prepare for a stem cell transplant, you receive chemotherapy to kill the diseased cells and malfunctioning bone marrow. Then, transplanted blood stem cells are put into your bloodstream. The transplanted stem cells find their way to your marrow, where — ideally — they begin producing new, healthy blood cells.

Since the 1950s when modern-day blood stem cell transplantation began, thousands of patients have enjoyed a second chance at life, thanks to a blood stem cell transplant.

Blood stem cells are special cells that enable your body to produce:

• white blood cells, that are need to fight infection;
• red blood cells, that carry oxygen to, and remove waste from, our body’s cells;
• platelets, that help blood clot

Blood stem cells mostly live in the bone marrow – the spongy tissue inside your bones. This is where stem cells divide to make new blood cells. Once blood cells mature, they leave the bone marrow and enter the bloodstream. A small number of stem cells also get into the bloodstream. These are called peripheral blood stem cells. Blood stem cells are also found in the discarded placenta and umbilical cord of newborn babies.

Doctors get hematopoietic stem cells from three different places:

• bone marrow
• the bloodstream
• umbilical cord blood after the cord is no longer attached to a newborn baby

A person who provides the stem cells is called a donor. Using donor cells is called an allogeneic transplant.

Stem cell transplants are used to give back stem cells when the bone marrow has been destroyed by disease, chemotherapy (chemo), or radiation. Depending on where the stem cells come from, this procedure may be called:

• Bone marrow transplant (BMT)
• Peripheral blood stem cell transplant
• Cord blood transplant

They can all be called hematopoietic stem cell transplants.

When stem cells come from a donor:

• Donors are often siblings. Sometimes, parents will keep a newborn’s umbilical cord blood for this purpose. But donors can also be other family members or even volunteers who aren’t related to a patient.
• Before they collect stem cells, doctors do tests to be sure the cells are a good match. If the patient and donor blood and tissue types don’t match, the patient’s body may reject the donor’s stem cells.

Donors don’t have to be other people — sometimes people can act as their own donor. This is called an autologous transplant.

When people donate their own stem cells:

• Doctors remove stem cells from either the blood or bone marrow. They do this before the person gets treatments like chemotherapy or radiation. This is called harvesting the stem cells. The stem cells are then frozen.
• After the person has had chemo or radiation, the thawed cells are put back inside the body. Doctors may transplant new stem cells more than once — it depends on what a patient needs.

Transplanting stem cells is a complicated process. It might take several months to decide if a patient is a good candidate and find the best donor.

For patients with certain cancers, the most effective treatment may be very high dosages of chemotherapy and/or total body irradiation. This therapy destroys not only the diseased cells, but blood stem cells as well. A stem cell transplant may be needed to “rescue” the patient from this life-threatening side effect.

A blood stem cell transplant may also be a treatment option for patients with certain inherited diseases such as immune deficiency diseases.

Why are stem cell transplants done?

Stem cell transplants can help people with:

• severe blood or immune system illnesses
• some kinds of cancer
• non-cancerous diseases, such as serious immune deficiency problems, autoimmune diseases (like lupus), or blood disorders (thalassemia or sickle cell disease, for example)

With cancer, the body’s cells grow in a way that’s not normal. These cells can spread throughout the body. With immune system diseases like lupus, the immune system goes haywire and may damage healthy cells in the body. To fix these problems, doctors destroy damaged or abnormal cells and replace them with transplanted stem cells. The stem cells then replicate and turn into healthy cells.

What makes stem cells so important?

Stem cells make the 3 main types of blood cells: red blood cells, white blood cells, and platelets.

You need all of these types of blood cells to keep you alive. For these blood cells to do their jobs, you need to have enough of each type in your blood.

Red blood cells (RBCs) carry oxygen away from the lungs to all of the cells in the body. They bring carbon dioxide from the cells back to the lungs to be exhaled.

A blood test called a hematocrit shows how much of your blood is made up of RBCs. The normal range is about 35% to 50% for adults. People whose hematocrit is below this level have anemia. This can make them look pale and feel weak, tired, and short of breath.

White blood cells (WBCs) help fight infections caused by bacteria, viruses, and fungi. There are different types of WBCs.

• Neutrophils are the most important type in fighting bacterial infections. The absolute neutrophil count (ANC) is a measure of the neutrophils in your blood. When your absolute neutrophil count drops below 1,000 per cubic millimeter (1,000/mm³) you have neutropenia, and you have a higher risk of infection. The danger is greatest when levels are below 500/mm³.
• Lymphocytes are another type of white blood cell. There are different kinds of lymphocytes, such as T lymphocytes (T cells), B lymphocytes (B cells), and natural killer (NK) cells. Some lymphocytes make antibodies to help fight infections. The body depends on lymphocytes to recognize its own cells and reject cells that don’t belong in the body, such as invading germs or cells that are transplanted from someone else.

Platelets (thrombocytes) are pieces of cells that seal damaged blood vessels and help blood to clot, both of which are important in stopping bleeding. A normal platelet count is usually between 150,000/cubic mm and 450,000/cubic mm, depending on the lab that does the test. A person whose platelet count drops below normal is said to have thrombocytopenia, and may bruise more easily, bleed longer, and have nosebleeds or bleeding gums. Spontaneous bleeding (bleeding with no known injury) can happen if a person’s platelet count drops lower than 20,000/mm3. This can be dangerous if bleeding occurs in the brain, or if blood begins to leak into the intestines or stomach.

What is the cost of a stem cell transplant?

Stem cell transplants cost a lot – some estimates say $350,000 to $800,000.

A transplant (or certain types of transplants) is still considered experimental for many types of cancer, especially many solid tumor cancers, so insurers might not cover the cost.

No matter what illness you have, it’s important to find out what your insurer will cover before deciding on a transplant, including donor match testing, cell collection, drug treatments, hospital stay, and follow-up care. Go over your transplant plan with them to find out what’s covered. Ask if the doctors and transplant team you plan to use are in their network, and how reimbursement will work. Some larger insurance companies have transplant case managers. If not, you might ask to speak with a patient advocate. You can also talk with financial or insurance specialists at your doctor’s office, transplant center, and hospital about what expenses you are likely to have. This will help you get an idea of what you might have to pay in co-pays and/or co-insurance.

Will insurance cover my stem cell transplant?

Prior to your stem cell transplant, your transplant center will contact your health insurance provider to request pre-approval for your transplant.

Whether the cost will be covered depends on the specific language in your insurance contract.

If your insurance provider denies coverage for your stem cell transplant, you can appeal that decision.

• The specific steps for filing an appeal are spelled out in your insurance contract and must be followed exactly.
• The financial coordinator at the transplant center may file the appeal on your behalf.
• If you are filing the appeal on your own, be sure to enlist the help of an attorney familiar with this area of law.

Common reasons for denying coverage are that the insurance provider considers the procedure experimental or not medically necessary. Often, additional information from the transplant center will resolve the issue.

Many insurance companies require their members to choose from a list of pre-approved transplant centers, which may not include the one you have chosen.

• Usually these are transplant centers that provide excellent care.
• Unless you can demonstrate that the center you chose offers superior service, it is unlikely you will be approved for a transplant at that center, even if the center is closer to your home.

Paying for out-of-pocket expenses

Although your insurance provider may pre-approve payment for the actual transplant, some procedures, such as donor search and testing costs, may not be covered. If you will be transplanted with cells from an unrelated donor, you may be eligible for donor search assistance funds from Be The Match (https://bethematch.org/about-us/financial-information/funding-patient-assistance/).

You may also have deductibles and co-pays that add to your out-of-pocket expenses. Prescription drugs, wigs and medical devices may or may not be covered by your plan.

Ask the financial coordinator at your transplant center to help you estimate your out-of-pocket expenses for medical treatment. If you have been assigned a case manager by your insurance company, he or she can help you estimate out-of-pocket expenses as well.

If you are traveling away from home for your transplant, you will have other expenses such as lodging, food and transportation to consider. Check Blood & Marrow Transplant Information Network Resource Directory (https://www.bmtinfonet.org/resource-directory#6) for organizations that may help you with some of these expenses.

If you have No Insurance

If you have no insurance, you may be eligible for a government sponsored insurance plan. Healthcare.gov is a web site designed to help you find insurance options.

The U.S. National Institutes of Health offers free transplants to those who qualify for one of their research protocols. To learn whether you qualify, contact the two branches who offer this service:

• National Cancer Institute Center for Cancer Research (https://ccr.cancer.gov/)
• National Heart, Lung and Blood Institute (https://www.nhlbi.nih.gov/)

Sometimes family members and friends will hold fundraisers to help you with your expenses. Several organizations such as HelpHopeLive (https://helphopelive.org/), the National Foundation for Transplants (https://transplants.org/) and the Children’s Organ Transplant Association (https://cota.org/) can help your loved ones organize these events.

In addition to the groups that provide financial assistance listed Blood & Marrow Transplant Information Network Resource Directory (https://www.bmtinfonet.org/resource-directory#6), your transplant center may have access to funds from local sources to help patients with transplant-related expenses, as well.

How long does it take to recover?

Before someone can go home from the hospital, doctors make sure that:

• the stem cell transplant succeeded
• the person is doing well

Going home doesn’t mean going back to normal life right away. The risk of infection means that it might be 3 months or more before the person can go back to school, visit the mall, or go to a sporting event. That’s because even a simple infection like a cold can be life-threatening for people whose immune systems need time to recover.

Stem cell transplant types

There are different types of blood stem cell transplants. The type of stem cell transplant varies according to the source of blood stem cells:

• Bone marrow transplants (BMT) use blood stem cells collected from the bone marrow.
• Peripheral blood stem cell transplants (PBSCT) use blood stem cells collected from the bloodstream.
• Cord blood transplants (CBT) use blood stem cells collected from the discarded placenta and umbilical cord of a new born baby.

The type of stem cell transplant also varies according to who provides the cells for the transplant:

• Autologous stem cell transplants use cells previously collected from the patient.
• Allogeneic stem cell transplants use cells provided by a donor.
• Syngeneic stem cell transplants use cells provided by an identical twin.

Prior to stem cell transplant, patients receive high dosages of chemotherapy and/or radiation to destroy their disease and make room for healthy new blood stem cells.

• If the dosage of chemotherapy and/or radiation is high enough to completely suppress the patient’s immune system, the procedure is called a myeloablative transplant
• If a patient receives less intensive dosages of chemotherapy and/or radiation, the procedure is called a reduced intensity or nonmyeloablative transplant.

Allogeneic stem cell transplant

An allogeneic stem cell transplant uses healthy blood stem cells from a donor to replace your diseased or damaged bone marrow. An allogeneic stem cell transplant is also called an allogeneic bone marrow transplant.

A donor may be a family member, an acquaintance or someone you don’t know. The blood stem cells used in an allogeneic stem cell transplant can be:

• Collected from the donor’s blood
• Collected from the bone marrow within a donor’s hipbone
• Collected from the blood of a donated umbilical cord

Before undergoing an allogeneic stem cell transplant, you’ll receive high doses of chemotherapy or radiation to destroy your diseased cells and prepare your body for the donor cells.

An allogeneic stem cell transplant may be an option for people with a variety of cancerous and noncancerous diseases, including:

• Acute leukemia
• Adrenoleukodystrophy
• Aplastic anemia
• Bone marrow failure syndromes
• Chronic leukemia
• Hemoglobinopathies
• Hodgkin’s lymphoma
• Immune deficiencies
• Inborn errors of metabolism
• Multiple myeloma
• Myelodysplastic syndromes
• Neuroblastoma
• Non-Hodgkin’s lymphoma
• Plasma cell disorders
• POEMS syndrome
• Primary amyloidosis

Undergoing an allogeneic stem cell transplant involves:

• Undergoing high doses of cancer treatment (conditioning). During the conditioning process, you’ll receive high doses of chemotherapy or radiation therapy to kill your cancer cells. What treatment you undergo depends on your disease and your particular situation. The cancer treatments used during the conditioning process carry a risk of side effects. Talk with your doctor about what you can expect from your treatment.
• Receiving an infusion of stem cells. Stem cells from a donor will be infused into your bloodstream, where they will travel to your bone marrow and begin creating new blood cells.
• Remaining under close medical care. After your transplant your care team will want to monitor you carefully for signs of complications. You may spend a few weeks in the hospital or nearby. Expect to undergo frequent blood tests and appointments to monitor your body’s response to the transplant.

It takes a few weeks for the donor cells to settle in your bone marrow and begin making new cells. You may receive blood transfusions until your bone marrow recovers.

Autologous stem cell transplant

An autologous stem cell transplant uses healthy blood stem cells from your own body to replace your diseased or damaged bone marrow. An autologous stem cell transplant is also called an autologous bone marrow transplant.

Using cells from your own body during your stem cell transplant offers some advantages over stem cells from a donor. For example, you won’t need to worry about incompatibility between the donor’s cells and your own cells if you have an autologous stem cell transplant.

An autologous stem cell transplant might be an option if your body is producing enough healthy bone marrow cells. Those cells can be collected, frozen and stored for later use.

Autologous stem cell transplants are typically used in people who need to undergo high doses of chemotherapy and radiation to cure their diseases. These treatments are likely to damage the bone marrow. An autologous stem cell transplant helps to replace the damaged bone marrow.

An autologous stem cell transplant is most often used to treat:

• Hodgkin’s lymphoma
• Multiple myeloma
• Non-Hodgkin’s lymphoma
• Plasma cell disorders

Undergoing an autologous stem cell transplant involves:

• Taking medications to increase the number of stem cells in your blood. You’ll receive medications that cause your stem cells to increase in number and to move out of your bone marrow and into your blood, where they can be easily collected.
• Filtering stem cells from your blood (apheresis). In order to collect your stem cells, a needle is inserted into a vein in your arm to draw out your blood. A machine filters out the stem cells and the rest of your blood is returned to your body. A preservative is added to your stem cells and then they’re frozen and stored for later use.
• Undergoing high doses of cancer treatment (conditioning). During the conditioning process, you’ll receive high doses of chemotherapy or radiation therapy — or sometimes both treatments — to kill your cancer cells. What treatment you undergo depends on your disease and your particular situation. The cancer treatments used during the conditioning process carry a risk of side effects. Talk with your doctor about what you can expect from your treatment.
• Receiving an infusion of stem cells. Your stem cells will be infused into your bloodstream, where they will travel to your bone marrow and begin creating new blood cells.

After your autologous stem cell transplant, you’ll remain under close medical care. You’ll meet with your care team frequently to watch for side effects and to monitor your body’s response to the transplant.

What diseases are being treated with stem cell transplant?

A blood stem cell transplant is used most often to treat patients with:

• Multiple myeloma
• Leukemia
• Non-Hodgkin lymphoma
• Hodgkin lymphoma
• Myelodysplastic syndrome (MDS)
• Myeloproliferative disorders such as myelofibrosis
• Severe aplastic anemia

A blood stem cell transplant can also be a treatment option for patients with:

• a genetic or inherited disorder, such as sickle cell disease or thalassemia
• an immune deficiency disease, such as Wiskott Aldrich Syndrome or severe combined immunodeficiency syndrome (SCIDS)
• a solid tumor, such as neuroblastoma
• an autoimmune disease, such as multiple sclerosis

Not all patients with these diseases require a stem cell transplant. Blood stem cell transplants are usually reserved for patients:

• who have a high risk of relapsing (the disease comes back) after less intensive treatment or
• who have already relapsed or
• whose quality of life can be improved by a blood stem cell transplant

Stem cell transplant process

Although the actual stem cell transplant takes only a few hours, the entire process, starting from advance preparations through recovery, takes many months.

The stem cell transplant process involves several steps:

• Choosing a transplant center
  • With nearly 200 transplants centers in the U.S. alone, finding the one that best suits your needs may seem like an overwhelming task. Fortunately, most patients can choose between several excellent transplant programs, each of which provides high quality medical care. You should begin by talking with your physician. Find out which transplant centers your doctor recommends, and why.
  • Transplant Center Directories:
    • Blood & Marrow Transplant Information Network has developed a transplant center directory (https://www.bmtinfonet.org/transplantcenters) to help you search for a transplant program in the U.S. that’s right for you. From the directory, you will be able to locate transplant centers by name, state, disease and type of transplant performed. The directory includes the number and type of transplants the center has performed in each of the past five years.
    • Be The Match ® also maintains a list of U.S. transplant centers (https://bethematch.org/tcdirectory/search/) that includes information about survival rates for patients undergoing an allogeneic transplant (using donor cells).
    • The U.S. Health Resources Service Administration (https://bloodcell.transplant.hrsa.gov/research/transplant_data/transplant_activity_report/year-specific_disease.pdf), provides historical data on transplants performed in the U.S. by disease.
    • If you are searching for a transplant center outside of the United States, Be The Match® maintains a list of international transplant centers (https://bethematch.org/patients-and-families/before-transplant/choose-a-transplant-center/international-transplant-centers/), with whom it is affiliated. The Center for International Blood & Marrow Transplant Research (CIBMTR) also maintains a list of international transplant centers (https://www.cibmtr.org/About/WhoWeAre/Centers/Pages/index.aspx).
• pre-transplant testing to determine if you are a good candidate for a transplant
• finding a blood stem cell donor, unless you will be using your own stem cells for transplant
• collecting stem cells for the transplant
• preparing you for transplant with chemotherapy and/or total body irradiation
• the day of transplant
• supportive care during the early recovery period
• long-term monitoring and follow-up care

How to prepare for a stem cell transplant:

• identify a full-time family caregiver or team of caregivers who can care for you while you are too ill to take care of yourself
• prepare yourself, and your family, emotionally for the transplant and recovery period
• plan who will manage the many expenses associated with a transplant as well as routine household bills while you are ill
• decide who will take care of family and household responsibilities while you are undergoing treatment
• decide if preserving your fertility after transplant is important and, if so, take steps to do that

If your child is the transplant patient, you will need to prepare the patient, siblings, teachers and classmates for what to expect during and after transplant.

Choosing a transplant center

When choosing a transplant center, there are some important things to consider:

• Is the transplant center accredited by the Foundation for Accreditation of Cellular Therapy (http://www.factwebsite.org/)? This agency conducts rigorous inspections of transplant programs and certifies programs that offer high quality care.
• Will your insurance cover your medical expenses at the transplant center you choose?
• What is the experience of the transplant team in treating patients with your disease? Some centers specialize in treating patients with a particular disease.
• What is the specific treatment plan the center will use for you – before, during and after transplant – and its side effects?
• Does the transplant center have a long-term follow-up program to help you with medical issues that may come up months or years after transplant?
• If the center is far from your home, how will your follow up care be coordinated with your local physicians?
• What kind of emotional support services are available for you, your caregiver and your family?
• What is the center’s success rate with transplants for patients with your particular disease?

When possible, visit the transplant centers you are considering and meet with the staff who will care for you including nurses, doctors and social workers. Don’t be afraid to get an opinion about the best treatment plan for you from more than one transplant center, and don’t be surprised if they don’t all agree. Along with your doctor, weigh the risks and benefits of each treatment plan before choosing the center that’s right for you.

If you’d like to talk with a patient who had a transplant at a particular medical center, ask the staff for some names and phone numbers. Most transplant centers will be happy to provide that information.

Success Rates at Transplant Centers

Be careful when discussing success rates with transplant centers, or comparing one center’s success rate to another. Success is measured in many different ways and does not always refer to the number of people cured.

For example:

• One transplant program may define success as the number of people alive one year after transplant.
• Another may define success as the number of people alive and disease free one year after transplant.
• A third might define it as the number of people alive three or more years after transplant.

Success rates are also affected by the type of patient a transplant center accepts. A center that accepts sicker or higher risk patients for transplant will likely report lower success rates than a center that accepts only prime candidates for transplant.

Pre-stem cell transplant test

A blood stem cell transplant is a rigorous medical procedure. In order to determine if you are a good candidate for a transplant, your medical team will consider your:

• age
• general physical condition
• diagnosis
• prior treatment history
• availability of a blood stem cell donor, unless you are using your own cells for transplant

Medical tests to determine if you are a good candidate for a stem cell transplant

Tests on your heart, lungs, kidneys and other vital organs will be done prior to transplant to ensure you can tolerate the procedure. These typically include:

• a MUGA scan/echocardiogram/EKG to measure your heart function
• a pulmonary function test to measure the health of your lungs
• a chest x-ray/CT scan to check for lung problems and infection
• blood work and urine tests to measure
• blood counts
• kidney function
• liver function
• past exposure to infectious diseases
• tests to check the status of your disease
• a full physical exam and health history
• a dental exam

You will also meet with a social worker or psychologist to discuss your emotional health, as well as a financial counselor who will help you with insurance approvals and financial issues.

How stem cells are collected

If you are providing the blood stem cells for a transplant, they will either be collected from your bloodstream (peripheral blood) or from your bone marrow.

Collecting stem cells from the bloodstream

The largest concentration of blood stem cells is in your bone marrow. However, the blood stem cells can be moved or “mobilized” out of the bone marrow into the bloodstream (peripheral blood) where they can be easily collected. Most transplants these days use stem cells collected from the bloodstream.

When blood stem cells are collected from the bloodstream, the procedure is called a peripheral blood stem cell collection or harvest.

Prior to the harvest, you will receive injections of a drug such as filgrastim (Neupogen®) or plerixifor (Mozobil®) over a four to five day period. These drugs move stem cells out of the bone marrow into the bloodstream.

Most people tolerate these drugs well, although mild, flu-like symptoms are common. The symptoms end a few days after the injections stop.

If you are collecting stem cells for your own transplant, chemotherapy drugs may be used to help move the stem cells out of your bone marrow into the bloodstream.

Peripheral blood stem cell collections are done in an outpatient clinic:

• You will sit in a comfortable chair or bed.
• A needle connected to thin, flexible tubing will be inserted into a vein in each of your arms.
• Blood will be withdrawn from one arm and passed through a machine that separates out the stem cells.
• The rest of the blood product will be returned to you through the tubing connected to the needle in your other arm.
• Each collection takes three to four hours.
• It can take one to three days to collect enough stem cells for transplant.
• If the collection takes more than a day, you can return home each night after the collection.

The procedure is painless. However, you may feel lightheaded, cold or numb around the lips. Some people feel cramping in their hands which is caused by the blood thinning agent used during the procedure. These symptoms cease when the procedure ends.

Collecting bone marrow

The procedure used to collect bone marrow for transplant is called a bone marrow harvest. It is a surgical procedure that takes place in a hospital operating room.

Typically it is done as an outpatient procedure:

• While you are under anesthesia, a needle will be inserted into your rear pelvic bone where a large quantity of bone marrow is located.
• The bone marrow will be extracted with a syringe.
• Several skin and bone punctures are required to extract sufficient bone marrow for transplant.
• There are no surgical incisions involved, only skin punctures where the needle was inserted.
• A sterile bandage will be applied to the site when the collection ends.

The amount of bone marrow harvested depends on the size of the patient and the concentration of blood stem cells in your marrow.

Typically one to two quarts of marrow and blood are harvested. While this may sound like a lot, your body can usually replace it in four weeks.

When the anesthesia wears off, you may feel some discomfort in your hip and lower back for several days. The pain is similar to what you would feel if you took a hard fall and bruised your hip. You may find sitting for a long period of time or climbing stairs uncomfortable for a few days. The pain is usually relieved with acetaminophen (Tylenol®).

Finding a bone marrow or stem cell donor

• If you need a transplant using bone marrow or stem cells from a donor, there are two options: a family member or an unrelated donor.
• If you are having a transplant using your own blood stem cells (autologous transplant) you will not need to search for a stem cell donor.
• If you are having a transplant that requires cells from a donor (allogeneic transplant) your transplant team will work with you to find a suitable donor. A donor search is not a process you initiate on your own.

The donor’s blood stem cells must have similar genetic markers as yours. These markers are called human leukocyte antigens or HLA.

Human Leukocyte Antigen Test (HLA)

Since you inherit your HLA type from your parents, a brother or sister with the same biological parents is the most likely candidate to be your donor. The HLA test is simple. In some cases, all that is required is a swab of the cells from your inner cheek. The sample is then sent to a special laboratory for testing. Some transplant centers ask potential related donors for a blood sample, instead of a cheek swab, so that they can run additional tests to determine compatibility.

Approximately one-third of patients in the U.S. have a sibling who can serve as their donor.

Your doctor may also ask other family members to be tested, although the likelihood that they will be a perfect match is small.

Determining whether a family member is a match requires a DNA test:

• This can be done by swabbing some cells from the inside of the cheek or by taking a blood sample.
• The sample is then sent to a special DNA testing laboratory.
• If the person is an HLA-match, a detailed physical examination and health history will be done to determine if he or she is healthy enough to be a donor.

Finding an unrelated bone marrow, stem cell or cord blood donor

If a family member cannot serve as your donor, your transplant center will begin a search for an unrelated donor.

• The search will include adult volunteer donors.
• If your transplant center performs umbilical cord blood transplants, a search of the international inventory of cord blood units will be conducted as well.
• Potential donors’ HLA type will be compared to yours to determine if they would be a good donor for you.

Be The Match® (https://bethematch.org/) coordinates unrelated donor searches in the U.S. Through its partnership with donor registries throughout the world.

Be The Match® provides access to nearly 27 million volunteer donors and more than 680,000 cord blood units worldwide.

Depending on your HLA type, the preliminary search may identify just a few or many potential matches. Your transplant doctor will select the most promising candidates for further testing.

You can get a preliminary look at the number of people in the donor registry who match you using the MatchView feature on the Be the Match® web site. Although this does not initiate a formal search for a donor, it can give you an idea of the likelihood of finding a match.

Mismatched bone marrow and stem cell donors

If a perfect match cannot be found for you, your doctor may suggest you use a mismatched donor. Mismatched donor transplants are very common, particularly for people with rare HLA types, and can lead to long-term success.

Your doctor may also suggest a haploidentical transplant. A haploidentical transplant is a transplant using cells from a related donor, such as a parent or child, who only half matches your HLA type. Historically, the risk of complications has been greater with a haploidentical transplant than with a transplant using blood stem cells from a well-matched donor. However new techniques have improved the safety of this procedure.

Watch a video about haploidentical transplants and cord blood transplants. The discussion about haploidentical transplants begins at 30:47.

Other criteria when choosing a bone marrow, stem cell or cord blood donor

Although HLA type is the most important consideration when choosing a suitable donor, your doctor will also take other factors into consideration including:

• age (younger is usually preferred over older)
• gender (male is often preferred over female)
• ff the donor is female, the number of times she has been pregnant
• history of infection, particularly with the cytomegalovirus (CMV)
• weight
• health history

Stem cell transplant procedure

Hospital admission or outpatient treatment

The hospital’s transplant team will decide if you need to be in the hospital to have your transplant, if it will be done in an outpatient center, or if you will be in the hospital just for parts of it. If you have to be in the hospital, you will probably go in the day before the transplant procedure is scheduled to start. Before conditioning treatment begins (see section below), the transplant team makes sure you and your family understand the process and want to go forward with it.

If you will be having all or part of your transplant as an outpatient, you’ll need to be very near the transplant center during the early stages. You’ll need a family member or loved one as a caregiver who can stay with you all the time. You and the caregiver will also need reliable transportation to and from the clinic. The transplant team will be watching you closely for complications, so expect to be at the clinic every day for a few weeks. You may still need to be in the hospital if your situation changes or if you start having complications.

To reduce the chance of infection during treatment, patients who are in the hospital are put in private rooms that have special air filters. The room may also have a protective barrier to separate it from other rooms and hallways. Some have an air pressure system that makes sure no unclean outside air gets into the room. If you’re going to be treated as an outpatient, you will get instructions on avoiding infection.

The transplant experience can be overwhelming. Your transplant team will be there to help you physically and emotionally prepare for the process and discuss your needs. Every effort will be made to answer questions so you and your family fully understand what will be happening to you as you go through transplant.

It’s important for you and your family to know what to expect, because once conditioning treatment begins (see the next section), there’s no going back – there can be serious problems if treatment is stopped at any time during transplant.

Conditioning treatment (chemo and/or radiation therapy)

Conditioning, also known as bone marrow preparation or myeloablation, is treatment with high-dose chemo and/or radiation therapy. It’s the first step in the transplant process and typically takes a week or two. It’s done for one or more of these reasons:

• To make room in the bone marrow for the transplanted stem cells
• To suppress the patient’s immune system to lessen the chance of graft rejection
• To destroy any remaining cancer cells in the patient’s body

The conditioning treatment is different for every transplant. Your treatment will be planned based on the type of cancer you have, the type of transplant, and any chemo or radiation therapy you’ve had in the past.

If chemo is part of your treatment plan, it will be given in your central venous catheter and/or as pills. If radiation therapy is planned, it’s given to the entire body (called total body irradiation or TBI). Total body irradiation may be given in a single treatment session or in divided doses over a few days.

This phase of the transplant can be very uncomfortable because very high treatment doses are used. Chemo and radiation side effects can make you sick, and it may take you months to fully recover. A very common problem is mouth sores that will need to be treated with strong pain medicines. You may also have nausea, vomiting, be unable to eat, lose your hair, and have lung or breathing problems.

Conditioning can also cause premature menopause in women and often makes both men and women sterile (unable to have children).

Infusion of stem cells

After the conditioning treatment, you’ll be given a couple of days to rest before getting the stem cells. They will be given through your central venous catheter, much like a blood transfusion. If the stem cells were frozen, you might get some drugs before the stem cells are given. These drugs are used to help reduce your risk of reacting to the preservatives that are used when freezing the cells.

If the stem cells were frozen, they are thawed in warm water then given right away. There may be more than 1 bag of stem cells. For allogeneic or syngeneic transplants, the donor cells may be harvested (removed) in an operating room, and then processed in the lab right away. Once they are ready, the cells are brought in and given to you – they’re not frozen. The length of time it takes to get all the stem cells depends on how much fluid the stem cells are in.

You will be awake for this process, and it doesn’t hurt. This is a big step and often has great meaning for recipients and their families. Many people consider this their rebirth or chance at a second life. They may celebrate this day as they would their actual birthday.

Infusion side effects

Side effects from the infusion are rare and usually mild. The preserving agent used when freezing the stem cells (called dimethylsulfoxide or DMSO) causes many of the side effects. For instance, you might have a strong taste of garlic or creamed corn in your mouth. Sucking on candy or sipping flavored drinks during and after the infusion can help with the taste. Your body will also smell like this. The smell may bother those around you, but you might not even notice it. The smell, along with the taste, may last for a few days, but slowly fades away. Often having cut up oranges in the room will offset the odor. Patients who have transplants from cells that were not frozen do not have this problem because the cells are not mixed with the preserving agent.

Other side effects you might have during and right after the stem cell infusion include:

• Fever or chills
• Shortness of breath
• Hives
• Tightness in the chest
• Low blood pressure
• Coughing
• Chest pain
• Less urine output
• Feeling weak

Again, side effects are rare and usually mild. If they do happen, they are treated as needed. The stem cell infusion must always be completed.

Stem cell transplant recovery

The recovery stage begins after the stem cell infusion. During this time, you and your family wait for the cells to engraft, or “take,” after which they start to multiply and make new blood cells. The time it takes to start seeing a steady return to normal blood counts varies depending on the patient and the transplant type, but it’s usually about 2 to 6 weeks. You’ll be in the hospital or visit the transplant center daily for at least a few weeks.

During the first couple of weeks you’ll have low numbers of red and white blood cells and platelets. Right after transplant, when your counts are the lowest, you may be given antibiotics to help keep you from getting infections. (This is called prophylactic antibiotics.) You may get a combination of anti-bacterial, anti-fungal, and anti-viral drugs. These are usually given until your white blood cell count reaches a certain level. Still, you can have problems, such as infection from too few white blood cells (neutropenia), or bleeding from too few platelets (thrombocytopenia). Many patients have high fevers and need IV antibiotics to treat serious infections. Transfusions of red blood cells and platelets are often needed until the bone marrow starts working and new blood cells are being made by the infused stem cells.

Except for graft-versus-host disease, which only happens with allogeneic transplants, the side effects from autologous, allogeneic, and syngeneic stem cell transplants are much the same. Problems may include stomach, heart, lung, liver, or kidney problems.

You might also go through feelings of distress, anxiety, depression, joy, or anger. Adjusting emotionally after the stem cells can be hard because of the length of time you feel ill and isolated from others.

You might feel as if you are on an emotional roller coaster during this time. Support and encouragement from family, friends, and the transplant team are very important to get you through the challenges after transplant.

Discharge from the hospital

Planning to go home

The discharge process actually begins weeks before your transplant. It starts with the transplant team teaching you and your primary (main) caregiver about:

• The precautions you’ll need to take
• Who will be your primary caregiver and what the job will be like, and who will be the back-up caregiver in case your main caregiver gets sick and can’t be near you
• How to prepare your home
• How to care for your central venous catheter
• How to take good care of your mouth and teeth
• What foods you should and shouldn’t eat
• Activities you can and can’t do
• When to call the transplant team or other health care providers

What has to happen before you can go home?

For the most part, transplant centers don’t send patients home until they meet the following criteria:

• No fever for 48 hours
• Able to take and keep down pills or other drugs for 48 hours
• Nausea, vomiting, and diarrhea are controlled with medicine
• Neutrophil count (absolute neutrophil count or ANC) is at least 500 to 1,000/mm3
• Hematocrit is at least 25% to 30%
• Platelet count is at least 15,000 to 20,000/mm3
• They have someone to help them at home and a safe and supportive home environment

If you do not meet all of these requirements, but still don’t need the intensive care of the transplant unit, you might be moved to another oncology unit. When you do go home, you might need to stay near the transplant center for some time, depending on your condition.

Rehabilitation

The process of stem cell transplant doesn’t end when you go home. You’ll feel tired, and some people have physical or mental health problems in the rehabilitation period. You might still be taking a lot of medicines. These ongoing needs must now be managed at home, so caregiver and friend/family support is very important.

Transplant patients are still followed closely during rehab. You might need daily or weekly exams along with things like blood tests, and maybe other tests, too. During early rehab, you also might need blood and platelet transfusions, antibiotics, or other treatments. At first you’ll need to see your transplant team often, maybe even every day, but you’ll progress to less frequent visits if things are going well. It can take 6 to 12 months, or even longer, for blood counts to get close to normal and your immune system to work well. During this time, your team will still be closely watching you.

Some problems might show up as much as a year or more after the stem cells were infused. They can include:

• Graft-versus-host disease (in allogeneic transplants)
• Infections
• Lung problems, such as pneumonia or inflammation that makes it hard to breathe
• Kidney, liver, or heart problems
• Low thyroid function
• Overwhelming tiredness (fatigue)
• Limited ability to exercise
• Slowed growth and development (in children)
• Cataracts
• Reproductive or sexual problems, like infertility, early menopause, pain or discomfort during sex, or loss of interest in sex
• New cancers caused by the transplant

Other problems can also come up, such as:

• Memory loss, trouble concentrating
• Emotional distress, depression, body image changes, anxiety
• Social isolation
• Changes in relationships
• Changes in how you view the meaning of life
• Feeling indebted to others
• Job and insurance discrimination

Your transplant team is still there to help you. It’s important that you talk to them about any problems you are having – they can help you get the support you need to manage the changes that you are going through. They can also help you know if problems are serious, or a normal part of recovery.

Stem cell transplant side effects

Problems soon after transplant

Many of the problems that can happen shortly after the transplant come from having the bone marrow wiped out by medicines or radiation just before the transplant. Others may be side effects of the conditioning treatments themselves.

This is not a complete list and you should tell your doctor or transplant team about any problems you have or changes you notice. Some of these problems can be life-threatening, so it’s important to be able to reach your doctor or transplant team at night, on weekends, and during holidays. Be sure you know how to do this.

Your transplant team can help you cope with side effects. Some can be prevented, and most can be treated to help you feel better.

Mouth and throat pain

Mucositis (inflammation or sores in the mouth) is a short-term side effect that can happen with chemo and radiation. It usually gets better within a few weeks after treatment, but it can make it very painful to eat and drink.

Good nutrition is important for people with cancer. If mouth pain or sores make it hard to eat or swallow, your transplant team will help you develop a plan to manage your symptoms.

Nausea and vomiting

Because chemotherapy drugs can cause severe nausea and vomiting, doctors often give anti-nausea medicines at the same time as chemo to try and prevent it. As much as possible, the goal is to prevent nausea and vomiting, because it’s easier to prevent it than it is to stop it once it starts. Preventive treatment should start before the chemo is given and should continue for as long as the chemo is likely to cause vomiting, which can be up to 7 to 10 days after the last dose.

No one drug can prevent or control chemo-related nausea and vomiting 100% of the time. In many cases, two or more medicines are used. You’ll need to tell your transplant team how well the medicines are controlling your nausea and vomiting. If they aren’t working, they will need to be changed.

Infection

During about the first 6 weeks after transplant, until the new stem cells start making white blood cells (engraftment), you can easily get serious infections. Bacterial infections are most common during this time, but viral infections that were controlled by your immune system can become active again. Fungal infections can also be an issue. And even infections that cause only mild symptoms in people with normal immune systems can be quite dangerous for you.

You may be given antibiotics to try to prevent infections until your blood counts reach a certain level. For instance, pneumocystis pneumonia (often called PCP) is a common infection that’s easy to catch. Even though the germ doesn’t harm people with normal immune systems, for others it can cause fever, cough, and serious breathing problems. Antibiotics are often used to keep transplant patients from getting this.

Your doctor may check you before the transplant for signs of certain infections that may become active after transplant, and give you special medicines to keep those germs under control. For example, the virus called CMV (cytomegalovirus) is a common cause of pneumonia in people who have had transplants. It mainly happens to people who were already infected with cytomegalovirus, or whose donor had the virus. If neither you nor your donor had cytomegalovirus, the transplant team might follow special precautions to prevent infection while you are in the hospital.

After engraftment, the risk of infection is lower, but it still can happen. It takes 6 months to a year after transplant for the immune systems of most patients to work as well as they should. It can take even longer for patients with graft-versus-host disease (GVHD, see below).

Because of the increased risk, you will be watched closely for signs of infection, such as fever, cough, shortness of breath, or diarrhea. Your doctor may check your blood often, and extra precautions will be needed to avoid exposure to germs. While in the hospital, everyone who enters your room must wash their hands well. They may also wear gowns, shoe coverings, gloves, and masks.

Since flowers and plants can carry bacteria and fungi, they’re not allowed in your room. For the same reason, you may be told not to eat certain fresh fruits and vegetables. All your food must be well cooked and handled very carefully by you and family members. Certain foods may need to be avoided for a while.

You may also be told to avoid contact with soil, feces (stool, both human and animal), aquariums, reptiles, and exotic pets. Your team may tell you to avoid being near disturbed soil, bird droppings, or mold. You will need to wash your hands after touching pets. Your family may need to move the cat’s litter box away from places you eat or spend your time.

Your transplant team will tell you and your family in detail about the precautions you need to follow. There are many viruses, bacteria, and fungi that can cause infection after your transplant.

Despite all these precautions, patients often develop fevers, one of the first signs of infection. If you do get a fever or other signs of infection, contact your doctor right away. Tests will be done to look for the cause of the infection (chest x-rays, urine tests, and blood cultures) and antibiotics will be started.

Bleeding and transfusions

After transplant, you’re at risk for bleeding because the conditioning treatment destroys your body’s ability to make platelets. (Platelets are the blood cells that help blood to clot.) While you wait for your transplanted stem cells to start working, your transplant team may have you follow special precautions to avoid injury and bleeding.

Platelet counts are low for at least 3 weeks after transplant. In the meantime, you might notice easy bruising and bleeding, such as nosebleeds and bleeding gums. If your platelet count drops below a certain level, a platelet transfusion may be needed. You’ll need to follow precautions until your platelet counts stay at safe levels.

It also takes time for your bone marrow to start making red blood cells, and you might need red blood cell transfusions from time to time as you recover.

Interstitial pneumonitis and other lung problems

Pneumonitis is a type of lung inflammation that’s most common in the first 100 days after transplant. But some lung problems can happen much later – even 2 or more years after transplant.

Pneumonia caused by infection happens more often, but pneumonitis may be caused by radiation, graft-versus-host disease, or chemo rather than germs. It’s caused by damage to the areas between the cells of the lungs (called interstitial spaces).

Pneumonitis can be severe, especially if total body irradiation was given with chemo as part of the conditioning treatment. Chest x-rays will be taken in the hospital to watch for pneumonitis as well as pneumonia. Some doctors will do breathing tests every few months if you have graft-versus-host disease (see next section).

You should report any shortness of breath or changes in your breathing to your doctor or transplant team right away. There are many other types of lung and breathing problems that also need to be handled quickly.

Graft-versus-host disease

Graft-versus-host disease (GVHD) can happen in allogeneic transplants when the immune cells from the donor see the recipient’s body as foreign. (Remember: The recipient’s immune system has mostly been destroyed by conditioning treatment and cannot fight back – the new stem cells make up most of the immune system after transplant.) The donor immune cells may attack certain organs, most often the skin, gastrointestinal (GI) tract, and liver. This can change the way the organs work and increase the chances of infection.

Graft-versus-host disease reactions are very common and can range from barely noticeable to life-threatening. Doctors think of graft-versus-host disease as acute or chronic. Acute graft-versus-host disease starts soon after transplant and lasts a short time. Chronic graft-versus-host disease starts later and lasts a long time. A person could have one, both, or neither type of graft-versus-host disease.

Acute graft-versus-host disease

Acute graft-versus-host disease can happen 10 to 90 days after a transplant, though the average time is around 25 days.

About one-third to one-half of allogeneic transplant recipients will develop acute graft-versus-host disease. It’s less common in younger patients and in those with closer HLA matches between donor and recipient.

The first signs are usually a rash, burning, and redness of the skin on the palms and soles. This can spread over the entire body. Other symptoms include:

• Nausea
• Vomiting
• Stomach cramps
• Diarrhea (watery and sometimes bloody)
• Loss of appetite
• Yellowing of the skin and eyes (jaundice)
• Abdominal (belly) pain
• Weight loss

Most cases are mild and can be treated. How well a person does depends on how bad the graft-versus-host disease is. Some cases of graft-versus-host disease can lead to death.

Doctors try to prevent acute graft-versus-host disease by giving drugs, such as steroids, certain monoclonal antibodies, methotrexate, cyclosporine, and tacrolimus to lessen the immune response. These drugs are given before acute graft-versus-host disease starts and can help prevent serious graft-versus-host disease. Still, mild graft-versus-host disease will almost always happen in allogeneic transplant patients. Other drugs in different combinations are being tested for graft-versus-host disease prevention.

The risk of acute graft-versus-host disease can also be lowered by removing a certain kind of immune cells, called T-cells, from the donor stem cells before the transplant. But this can also increase the risk of viral infection, leukemia relapse, and graft failure (which is discussed later). Researchers are looking at new ways to remove only certain cells, called alloactivated T-cells, from donor grafts. This would reduce the severity of graft-versus-host disease and still let the donor T-cells destroy any cancer cells left. Preventing and managing graft-versus-host disease are major priorities for research.

Chronic graft-versus-host disease

Chronic graft-versus-host disease can start anywhere from about 90 to 600 days after the stem cell transplant. A rash on the palms of the hands or the soles of the feet is often the earliest sign. The rash can spread and is usually itchy and dry. In severe cases, the skin may blister and peel, like a bad sunburn. A fever may also develop. Other symptoms of chronic graft-versus-host disease can include:

• Decreased appetite
• Diarrhea
• Abdominal (belly) cramps
• Weight loss
• Yellowing of the skin and eyes (jaundice)
• Enlarged liver
• Bloated abdomen (belly)
• Pain in the upper right part of the abdomen (belly)
• Increased levels of liver enzymes in the blood (seen on blood tests)
• The skin feels tight
• Dry, burning eyes
• Dryness or painful sores in the mouth
• Burning sensations when eating acidic foods
• Bacterial infections
• Blockages in the smaller airways of the lungs

Chronic graft-versus-host disease is treated with medicines that suppress the immune system, much like those used for acute graft-versus-host disease. These drugs can increase your risk of infection for as long as you are treated for graft-versus-host disease. Most patients with chronic GVHS can stop the immunosuppressive drugs after their symptoms improve.

Hepatic veno-occlusive disease

Hepatic veno-occlusive disease is a serious problem in which tiny veins and other blood vessels inside the liver become blocked. It’s not common, and it only happens in people with allogeneic transplants, and mainly in those who got the drugs busulfan or melphalan as part of conditioning.

Hepatic veno-occlusive disease usually happens within about 3 weeks of conditioning. It’s more common in older people who had liver problems before the transplant, and in those with acute graft-versus-host disease. It starts with yellowing skin and eyes, dark urine, tenderness below the right ribs (this is where the liver is), and quick weight gain (mostly from fluid that bloats the belly). Sometimes it can result in liver failure and death.

Doctors have found that giving busulfan in the vein (IV) rather than by mouth may reduce the risk of hepatic veno-occlusive disease. New ways to prevent and treat this problem are being tested.

Graft failure

Grafts fail when the body does not accept the new stem cells (the graft). The stem cells that were given do not go into the bone marrow and multiply like they should. Graft failure is more common when the patient and donor are not well matched and when patients get stem cells that have had the T-cells removed. It can also happen in patients who get a low number of stem cells, such as a single umbilical cord unit. Still, it’s not very common.

Graft failure can lead to serious bleeding and/or infection. It’s suspected in patients whose counts do not start going up within 3 to 4 weeks of a bone marrow or peripheral blood transplant, or within 7 weeks of a cord blood transplant.

It may be treated by a second dose of stem cells, if available. Grafts rarely fail, but if they do it can result in death.

Transplant problems that may show up later

The type of problems that can happen after a transplant depend on many factors, such as the type of transplant done, the conditioning treatment used, the patient’s overall health, the patient’s age when the transplant was done, the length and degree of immune system suppression, and whether chronic graft-versus-host-disease (GVHD) is present and how bad it is. The problems can be caused by the conditioning treatment (the pre-transplant chemotherapy and radiation therapy), especially total body irradiation, or by other drugs used during transplant (such as the drugs that may be needed to suppress the immune system after transplant). Possible long-term risks of transplant include:

• Organ damage
• Relapse (the cancer comes back)
• Secondary (new) cancers
• Abnormal growth of lymph tissues
• Infertility (the inability to produce children)
• Hormone changes, such as changes in the thyroid or pituitary gland
• Cataracts (clouding of the lens of the eye, which causes vision loss)

The medicines used in transplants can harm the body’s organs, such as the heart, lungs, kidneys, liver, bones/joints, and nervous system. You may need careful follow-up with close monitoring and treatment of the long-term organ problems that the transplant can cause. Some of these, like infertility, should be discussed before the transplant, so you can prepare for them.

It’s important to find and quickly treat any long-term problems. Tell your doctor right away if you notice any changes or problems. Physical exams by your doctor, blood work, imaging tests, lung/breathing studies, and other tests will help look for and keep tabs on organ problems.

As transplant methods have improved, more people are living longer and doctors are learning more about the long-term results of stem cell transplant. Researchers continue to look for better ways to care for these survivors to give them the best possible quality of life.

Cancer relapse

The goal of a stem cell transplant in cancer is to prolong life and even cure the cancer. But in some cases, the cancer comes back (relapses). Relapse can happen a few months to a few years after transplant. It happens much more rarely 5 or more years after transplant.

After relapse, treatment options are often quite limited. A lot depends on your overall health at that point, and whether the type of cancer you have responds well to drug treatment. Treatment for those who are otherwise healthy and strong may include chemotherapy or targeted therapy. Some patients who have had allogeneic transplants may be helped by getting white blood cells from the same donor (this is called donor lymphocyte infusion) to boost the graft-versus-cancer effect. Sometimes a second transplant is possible. But most of these treatments pose serious risks even to healthier patients, so those who are frail, older, or have chronic health problems are often unable to get them.

Other options may include palliative (comfort) care, or a clinical trial of an investigational treatment. It’s important to know what the expected outcome of any further treatment might be, so talk with your doctor about the purpose of the treatment. Be sure you understand the pros and cons before you decide.

Secondary cancers (new cancers caused by treatment)

Along with the possibility of the original cancer coming back (relapse) after it was treated with a stem cell transplant, there is also a chance of having a second cancer after transplant. Studies have shown that people who have had allogeneic transplants have a higher risk of second cancer than people who got a different type of stem cell transplant.

Cancers that happen a few months after transplant are mainly lymphomas, especially the B-cell types. These seem to be caused by a common virus known as Epstein-Barr virus, or EBV. The immune system can normally keep the virus under control, but Epstein-Barr virus can cause cancer — especially when the immune system is being suppressed with drugs, as it is after allogeneic transplant.

Acute leukemia is a type of cancer that can develop a few years after stem cell transplant. Another disorder of the bone marrow called myelodysplasia or myelodysplastic syndrome, in which the bone marrow makes defective blood cells, can also happen a few years after transplant. Myelodysplasia is generally a mild form of cancer, but it can become more aggressive in some people.

Secondary cancers that happen many years later may include solid tumor cancers, often of the skin, mouth, brain, liver, cervix, thyroid, breast, and bone.

Risk factors for developing a second cancer are being studied and may include:

• Radiation (such as total body irradiation) and high-dose chemo as part of the conditioning treatment
• Previous chemo or radiation treatment that was not part of the transplant process
• Immune system problems (such as graft-versus-host disease, HLA-mismatched allogeneic transplant, and immunosuppressant therapy)
• Being older than age 40 at the time of transplant
• Infection with viruses such as Epstein-Barr (EBV), cytomegalovirus (CMV), hepatitis B (HBV), or hepatitis C (HCV)

Some second cancers can show up a few months or a few years after transplant. But second cancers can take many years to develop, so the best studies are in those who have lived a long time after treatment.

Successfully treating a first cancer gives a second cancer time (and the chance) to develop. No matter what type of cancer is treated, and even without the high doses used for transplant, treatments like radiation and chemo can lead to a second cancer in the future.

Post-transplant lymphoproliferative disorder

Post-transplant lymphoproliferative disorder (PTLD) is an out-of-control growth of lymph cells, actually a type of lymphoma, that can develop after an allogeneic stem cell transplant. It’s linked to a malfunction of T-cells (a type of white blood cell that is part of the immune system) and the presence of Epstein-Barr virus (EBV). T-cells normally help rid the body of cells that contain viruses. When the T-cells aren’t working well, Epstein-Barr virus-infected B-lymphocytes (a type of white blood cell) can grow and multiply. Most people are infected with Epstein-Barr virus at some time during their lives, but the infection is controlled by a healthy immune system. The conditioning treatment given before transplant weakens the immune system, allowing the Epstein-Barr virus infection to get out of control, which can lead to a post-transplant lymphoproliferative disorder.

Still, post-transplant lymphoproliferative disorder after allogeneic stem cell transplant is fairly rare. It most often happens within 1 to 6 months after allogeneic stem cell transplant, when the immune system is still very weak.

Post-transplant lymphoproliferative disorder is life-threatening. It may show up as lymph node swelling, fever, and chills. There’s no one standard treatment, but it’s often treated by cutting back on immunosuppressant drugs to let the patient’s immune system fight back. Other treatments include white blood cell (lymphocyte) transfusions to boost the immune response, using drugs like rituximab to kill the B cells, and giving anti-viral drugs to treat the Epstein-Barr virus.

Even though post-transplant lymphoproliferative disorder doesn’t often happen after transplant, it’s more likely to occur with less well-matched donors and when strong suppression of the immune system is needed. Studies are being done to identify risk factors for post-transplant lymphoproliferative disorder and look for ways to prevent it in transplant patients who are at risk.

Stem cell transplant and having children

Most people who have stem cell transplants become infertile (unable to have children). This is not caused by the stem cells that are transplanted, but rather by the high doses of chemo and/or radiation therapy used. These treatments affect both normal and abnormal cells, and often damage reproductive organs.

Although most patients are infertile after transplant, a number of transplant survivors have had children after transplant without any medical intervention.

If having children is important to you, or if you think it might be important in the future, talk to your doctor before treatment about ways to protect your fertility. Your doctor may be able to tell you if a particular treatment will be likely to cause infertility.

After chemo or radiation, women may find their menstrual periods become irregular or stop completely. This doesn’t always mean they cannot get pregnant, so birth control should be used before and after a transplant. The drugs used in transplants can harm a growing fetus.

The drugs used during transplant can also damage sperm, so men should use birth control to avoid starting a pregnancy during and for some time after the transplant process. Transplants may cause temporary or permanent infertility for men as well. Men might consider storing their sperm before having a transplant. This process can take several days. Fertility returns in some men, but the timing is unpredictable.

Options for Males to Preserve Fertility

Most males can bank their sperm before transplant. Even if you don’t think you want children, sperm banking is worth considering.

You may change your mind later in life, and having sperm banked preserves that option.

Discussing sperm banking with an adolescent who needs a transplant can be challenging and emotionally upsetting for the young man. Consider consulting the hospital social worker or a therapist about how best to approach this delicate matter with your child.

If you do not bank your sperm prior to transplant, a procedure called testicular sperm retrieval may be an option after transplant. Even if there is no sperm in the ejaculate, there may be viable sperm in the testes which can be extracted and used to fertilize a woman’s egg and create an embryo.

Testicular sperm retrieval may also be considered prior to transplant if there is no sperm in the ejaculate due to prior treatment. This may not be an option for patients who need to proceed to transplant quickly.

Options for Females to Preserve Fertility

For women, it may be possible to collect eggs prior to transplant, fertilize them with male sperm to create embryos, and then freeze the embryos for later use. This procedure requires several weeks and may not be an option for patients who need to proceed quickly to transplant.

After transplant, a woman may be able to become pregnant by having the embryos implanted in her womb. This procedure, called in-vitro fertilization, is not always successful but several transplant survivors have conceived children by this method.

It is also possible to collect and freeze a woman’s eggs without fertilizing them with male sperm. However, unfertilized eggs are less likely to survive the freezing and thawing process than fertilized eggs.

Another experimental option for women is freezing ovarian tissue. Ovarian tissue is removed during a short, outpatient surgical procedure and then frozen. The tissue can later be implanted into a woman’s ovary where it may produce eggs.

Stem cell transplant success rate

For allogenic stem cell transplant, overall survival at day 100 significantly improved for patients with myeloid leukemias (AML) in first complete remission after myeloablative sibling allogenic stem cell transplant (85% to 94%) and unrelated allogenic stem cell transplant (63% to 86%); 1-year overall survival improved among those undergoing unrelated allogenic stem cell transplant (48% to 63%) but not among those undergoing sibling allogenic stem cell transplant ¹. Similar results were seen for acute lymphoblastic (ALL) and myelodysplastic syndrome (MDS). Day-100 overall survival after cord blood allogenic stem cell transplant improved significantly from 60% to 78% for acute lymphoblastic (ALL) and myeloid leukemias (AML), myelodysplastic syndrome (MDS), and chronic myeloid leukemia. Use of reduced-intensity regimens increased, yielding overall survival rates similar to those of myeloablative regimens ¹.

Stem cell transplant for cancer

Stem cell transplants do not usually work against cancer directly. Instead, they help you recover your ability to produce stem cells after treatment with very high doses of radiation therapy, chemotherapy, or both.

Stem cell transplants, including peripheral blood, bone marrow, and cord blood transplants, can be used to treat cancer. Stem cell transplants are most often used for cancers affecting the blood or immune system, such as leukemia, lymphoma, or multiple myeloma.

In multiple myeloma and some types of leukemia, the stem cell transplant may work against cancer directly. This happens because of an effect called graft-versus-tumor that can occur after allogeneic transplants. Graft-versus-tumor occurs when white blood cells from your donor (the graft) attack any cancer cells that remain in your body (the tumor) after high-dose treatments. This effect improves the success of the treatments.

Why would someone with cancer need a stem cell transplant?

Stem cell transplants are used to replace bone marrow that has been destroyed by cancer or destroyed by the chemo and/or radiation used to treat the cancer.

In some cancers, such as certain leukemias, multiple myeloma, and some lymphomas, a stem cell transplant can be an important part of treatment. It works like this: high doses of chemo (sometimes along with radiation), work better than standard doses to kill cancer cells. But high doses can also kill all the stem cells and cause the bone marrow to completely stop making blood cells, which we need to live. This is where stem cell transplants come in. The transplanted stem cells replace the body’s stem cells after the bone marrow and its stem cells have been destroyed by treatment. Transplant lets doctors use much higher doses of chemo to try to kill all of the cancer cells.

A stem cell transplant from another person can also help treat certain types of cancer in a way other than just replacing stem cells. Donated cells can often find and kill cancer cells better than the immune cells of the person who had the cancer ever could. This is called the “graft-versus-cancer” or “graft-versus-leukemia” effect. It means that certain kinds of transplants actually help fight the cancer cells, rather than simply providing normal blood cells.

Stem cell transplant for leukemia

Stem cell transplant for Acute Myeloid Leukemia

The doses of chemotherapy drugs that doctors can give to treat acute myeloid leukemia (AML) are limited by the serious side effects they can cause. Even though higher doses of these drugs might kill more cancer cells, they can’t be given because they could severely damage the bone marrow, which is where new blood cells are formed. This could lead to life-threatening infections, bleeding, and other problems caused by low blood cell counts.

Doctors can sometimes use a stem cell transplant also called a bone marrow transplant, to give higher doses of chemotherapy than could normally be given. (Sometimes radiation therapy is given as well.) After the treatment is finished, the patient gets an infusion of blood-forming stem cells to restore their bone marrow.

The blood-forming stem cells used for a transplant can come either from blood or from bone marrow. Sometimes stem cells from a baby’s umbilical cord blood are used.

For most patients with acute myeloid leukemia, especially those at higher risk of having the leukemia return after treatment, using an allogeneic stem cell transplant is preferred over an autologous stem cell transplant. Leukemia is a disease of the blood and bone marrow, so giving the patient his or her own cells back after treatment may mean giving them back some leukemia cells as well. Donor cells are also helpful because of the graft-versus-leukemia effect. When the donor immune cells are infused into the body, they may recognize any remaining leukemia cells as being foreign to them and attack them. This effect doesn’t happen with autologous stem cell transplants.

Allogeneic transplants can have serious risks and side effects, so patients typically need to be younger and relatively healthy to be good candidates. Another challenge is that it can sometimes be difficult to find a matched donor.

Non-myeloablative transplant (mini-transplant): Many older people can’t tolerate a standard allogeneic transplant that uses high doses of chemo. Some may still be able to get a non-myeloablative transplant (also known as a mini-transplant or reduced-intensity transplant), where they get lower doses of chemo and radiation that don’t completely destroy the cells in their bone marrow. They then get the allogeneic (donor) stem cells. These cells enter the body and establish a new immune system, which sees the leukemia cells as foreign and attacks them (a graft-versus-leukemia effect).

A non-myeloablative transplant can still sometimes work with much less toxicity. In fact, a patient can get the transplant as an outpatient. The major complication is graft-versus-host disease.

Many doctors still consider this an experimental procedure for acute myeloid leukemia, and it is being studied to determine how useful it may be.

Autologous transplants are sometimes used for people with acute myeloid leukemia who are in remission after initial treatment and who don’t have a matched donor for an allogeneic transplant. Some doctors feel that it is better than standard “consolidation” chemotherapy for these people, but not all doctors agree with this.

Autologous transplants are generally easier for patients to tolerate than allogeneic transplants, because they are getting their own cells back, which lowers the risk of some complications. But the high-dose chemo can still cause major side effects. This type of transplant can be done in any otherwise healthy person, although patients who are very old or have other health problems might not be suitable.

One problem with autologous transplants is that it’s hard to separate normal stem cells from leukemia cells in the bone marrow or blood samples. Even after purging (treating the stem cells in the lab to try to kill or remove any remaining leukemia cells), there is the risk of returning some leukemia cells with the stem cell transplant.

Stem cell transplant for Acute Lymphocytic Leukemia

Standard doses of chemotherapy (chemo) aren’t always able to cure acute lymphocytic leukemia (ALL). Even though higher doses of chemo drugs might be more effective, they can’t be given because they could severely damage the bone marrow, which is where new blood cells are formed. This could lead to life-threatening infections, bleeding, and other problems due to low blood cell counts.

A stem cell transplant allows doctors to use higher doses of chemo (sometimes along with radiation) to kill the cancer cells. After these treatments are finished, the patient gets an infusion (transplant) of blood-forming stem cells to restore their bone marrow.

Blood-forming stem cells used for a transplant are obtained either from the blood, from the bone marrow, or from a baby’s umbilical cord blood. Most often, stem cells from the blood are used.

Stem cell transplant for Chronic Myelomonocytic Leukemia

Stem cell transplant is the only treatment that can cure chronic myelomonocytic leukemia (chronic myelomonocytic leukemia). In this treatment, the patient gets high-dose chemotherapy often along with radiation to the entire body to kill the cells in the bone marrow (including the abnormal bone marrow cells). Then the patient is given new, healthy blood-forming stem cells. The 2 main types of stem cell transplant are: allogeneic and autologous.

In an autologous stem cell transplant, after the bone marrow is destroyed, the patient gets back their own stem cells. This type of transplant is not a standard treatment for patients with chronic myelomonocytic leukemia because their bone marrow has abnormal stem cells.

For an allogeneic stem cell transplant, the patient gets blood-forming stem cells from another person — the donor. The best results are when the donor’s cells are closely matched to the patient’s cell type and the donor is closely related to the patient, such as a brother or sister. Less often, an unrelated donor is matched to the patient.

Allogeneic stem cell transplant can have serious, even fatal, side effects and so is rarely used in elderly patients. Because of these side effects, some doctors only use this treatment for people younger than a certain age.

A special type of allogeneic transplant, a non-myeloablative allogeneic stem cell transplant, may be an option for older patients. This type of transplant is sometimes called a mini-transplant or a mini-allo. In this type, the doses of chemo and/or radiation that are given are lower than those used for a standard allogeneic transplant. These doses are not high enough to kill all the bone marrow cells, but they kill just enough to allow the donor cells to take hold and grow in the bone marrow. The lower doses of chemo and/or radiation cause fewer side effects, which makes this type of transplant easier for older patients to tolerate. Still, it has some serious side effects.

For now, allogeneic stem cell transplant is the only treatment that can cure some patients with chronic myelomonocytic leukemia, but not all patients who get a transplant are cured. And patients can die from complications of this treatment. Also, many people with chronic myelomonocytic leukemia are not able to get this treatment.

Stem cell transplant for Chronic Myeloid Leukemia

Stem cell transplant is not a common treatment for chronic meyloid leukemia (CML) today. In the past, before tyrosine kinase inhibitors (TKIs) were available, stem cell transplant was often used to treat chronic meyloid leukemia (CML). Now, tyrosine kinase inhibitors are the standard treatment, and transplants are being used far less often.

Because allogeneicstem cell transplant offers the only proven chance to cure chronic meyloid leukemia (CML), doctors may still recommend a transplant for younger patients, particularly children. Transplant is more likely to be considered for those with an available matched donor, like a well-matched brother or sister.

Transplant may also be recommended if chronic meyloid leukemia (CML) is not responding well to tyrosine kinase inhibitors. It’s also an important option for people with chronic meyloid leukemia (CML) that’s advancing to or diagnosed in the accelerated or blast phases.

Allogeneic stem cell transplant is the only known cure for chronic meyloid leukemia (CML). Still, this type of transplant can cause severe or even life-threatening complications and side effects, and it’s often not be a good option in people who are older or have other health problems.

Stem cell transplant for Chronic Lymphocytic Leukemia

In most cases, chemotherapy, immunotherapy and/or targeted therapy can reduce the number of leukemia cells in chronic lymphocytic leukemia (CLL) and improve symptoms. These treatments can often control chronic lymphocytic leukemia for a long time. But even if all signs of leukemia go away, the disease often comes back later. This is especially true of the types of chronic lymphocytic leukemia that are harder to treat , such as those with chromosome 17 deletions and TP53 mutations, as well as chronic lymphocytic leukemia that doesn’t respond to standard treatments. Higher doses of chemo might be work better, but they often can’t be used because they could severely damage bone marrow, where new blood cells are made. This could lead to life-threatening infections, bleeding, and other problems linked to low blood cell counts.

A stem cell transplant allows doctors to use higher doses of chemo, sometimes along with radiation therapy, to treat chronic lymphocytic leukemia. After these treatments, the patient receives a transplant of blood-forming stem cells to restore the bone marrow.

Blood-forming stem cells used for a transplant come either from the blood (for a peripheral blood stem cell transplant), from the bone marrow (for a bone marrow transplant, or BMT), or from umbilical cord blood. Bone marrow transplant was common in the past, but today it has largely been replaced by peripheral blood stem cell transplant.

It’s not yet clear how helpful stem cell transplants are in patients with chronic lymphocytic leukemia. When transplant is done, it’s most often as part of a clinical trial.

Stem cell transplant for Hodgkin lymphoma

Stem cell transplants are sometimes used for hard-to-treat Hodgkin lymphoma, such as disease that doesn’t go away completely after chemotherapy (chemo) and/or radiation or lymphoma that comes back after treatment.

The doses of chemo drugs given to patients normally are limited by the side effects these drugs cause. Higher doses can’t be used, even if they might kill more cancer cells, because they would severely damage the bone marrow, where new blood cells are made.

A stem cell transplant lets doctors give higher doses of chemo (sometimes along with radiation therapy). This is because after getting high-dose chemo, the patient receives a transplant of blood-forming stem cells to rebuild the bone marrow.

The blood-forming stem cells used for a transplant can come either from the blood or from the bone marrow. Today, most transplants are done with cells that are taken out of the blood and are called peripheral stem cell transplants.

Stem cell transplant for multiple myeloma

In a stem cell transplant, the patient gets high-dose chemotherapy to kill the cells in the bone marrow. Then the patient receives new, healthy blood-forming stem cells. When stem cell transplants were first developed, the new stem cells came from bone marrow, and so this was known as a bone marrow transplant. Now, stem cells are more often collected from blood (a peripheral blood stem cell transplant).

Stem cell transplant is commonly used to treat multiple myeloma. Before the transplant, drug treatment is used to reduce the number of myeloma cells in the patient’s body.

Stem cell transplants can be autologous or allogeneic.

Autologous stem cell transplants

For an autologous stem cell transplant, the patient’s own stem cells are removed from his or her bone marrow or peripheral blood before the transplant. The cells are stored until they are needed for the transplant. Then, the person with myeloma gets treatment such as high-dose chemotherapy, sometimes with radiation, to kill the cancer cells. When this is complete, the stored stem cells are given back to the patient into their blood through a vein.

This type of transplant is a standard treatment for patients with multiple myeloma. Although an autologous transplant can make the myeloma go away for a time (even years), it doesn’t cure the cancer, and often the myeloma returns.

Some doctors recommend that patients with multiple myeloma have 2 autologous transplants, 6 to 12 months apart. This approach is called tandem transplant. Studies show that this may help some patients more than a single transplant. The drawback is that it causes more side effects and as a result can be riskier.

Allogeneic stem cell transplants

In an allogeneic stem cell transplant, the patient gets blood-forming stem cells from another person – the donor. The best treatment results occur when the donor’s cells are closely matched to the patient’s cell type and the donor is closely related to the patient, such as a brother or sister. Allogeneic transplants are much riskier than autologous transplants, but they may be better at fighting the cancer. That’s because transplanted (donor) cells may actually help destroy myeloma cells. This is called a graft vs. tumor effect. In studies of multiple myeloma patients, those who got allogeneic transplants often did worse in the short term than those who got autologous transplants. At this time, allogeneic transplants are not considered a standard treatment for myeloma, but may be done as a part of a clinical trial.

Stem cell side effects

The early side effects from a stem cell transplant are similar to those from chemotherapy and radiation, only more severe. One of the most serious side effects is low blood counts, which can lead to risks of serious infections and bleeding.

The most serious side effect from allogeneic transplants is graft-versus-host disease (or GVHD). This occurs when the new immune cells (from the donor) see the patient’s tissues as foreign and attack them. Graft-versus-host disease can affect any part of the body and can be life threatening.

References

1. Significant Improvement in Survival After Allogeneic Hematopoietic Cell Transplantation During a Period of Significantly Increased Use, Older Recipient Age, and Use of Unrelated Donors. Theresa Hahn, Philip L. McCarthy Jr, Anna Hassebroek, Christopher Bredeson, James L. Gajewski, Gregory A. Hale, Luis M. Isola, Hillard M. Lazarus, Stephanie J. Lee, Charles F. LeMaistre, Fausto Loberiza, Richard T. Maziarz, J. Douglas Rizzo, Steven Joffe, Susan Parsons, and Navneet S. Majhail. Journal of Clinical Oncology 2013 31:19, 2437-2449