Peripheral blood stem cell transplantation is a treatment which involve first harvesting specific cells called stem cells from the peripheral blood of the donor. These cells are harvested by a type of filtration and then preserved, usually by freezing, and finally given to the recipient after he or she has received intensive treatment.
The stem cells are usually given instead of bone marrow cells. They go to the recipient’s bone marrow spaces and rebuild the bone marrow after the intensive treatment is over.
The treatment does not involve surgery, but is nevertheless a form of transplantation.
What are stem cells?
Stem cells are small, round cells with a squat nucleus and scant surrounding cytoplasm. Although unremarkable in appearance, stem cells can perform what have been called “acts of biological resurrection.”
What do stem cells do?
Whereas other types of cells in the body have a limited lifespan and die after dividing their endowed number of times, a stem cell can reproduce forever.
The stem cell is immortal (in cellular terms). A stem cell can forgo immortality and differentiate. By doing so, it can turn into an ordinary blood cell, like a red blood cell (an erythrocyte), a white blood cell (a leukocyte), or a large cell (a megakaryocyte) that fragments into the platelets needed for blood to clot.
What is the value of stem cells for transplantation?
A relatively small number of stem cells can miraculously repopulate the whole bone marrow, provide an endless supply of stem cells, reconstitute the entire repertory of blood cells, and restore that portion of the immune system.
Where do the stem cells come from for transplantation?
Under normal circumstances, stem cells are rarely seen in the blood stream.
To recruit enough stem cells into the blood, stem cells are lured out of the bone marrow by a special regimen of drugs and thereby coaxed into entering the peripheral blood (the blood stream).
Why would someone need a stem cell transplant?
Stem cell transplants are used to replace bone marrow that isn’t working or has been destroyed by disease, chemo, or radiation.
In some diseases, like leukemia, aplastic anemia, certain inherited blood diseases, and some diseases of the immune system, the stem cells in the bone marrow don’t work the way they should.
Damaged or diseased stem cells can make too few blood cells, too few immune cells, or too many abnormal cells. Any of these problems can cause the body to not have enough normal red blood cells, white blood cells, or platelets.
A stem cell transplant may help correct these problems.
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, which is sometimes given with radiation, work better than standard doses to kill cancer cells.
But high doses can also 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 cells replace the body’s source of blood cells after the bone marrow and its stem cells have been destroyed by the treatment.
This 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 replacing the blood cells.
How is the patient “prepared” for the transplantation?
Before the transplant is done, the patient receives high-dose chemotherapy and/or radiation therapy over several days to destroy diseased cells (the leukemic cells, lymphoma cells, solid tumor cells, the diseased immune system cells in scleroderma, etc.)
How is the transplantation actually done?
Once the chemotherapy is gone, the stem cells are defrosted and returned to the patient as a blood transfusion.
They are already biologically programmed to migrate to the bone marrow, where they can produce new blood and immune cells and replace the cells destroyed by the treatment.
The stem-cell preparation is infused into a vein and, once there in the blood stream, the stem cells act like homing pigeons and head straight for the bone marrow space.
Weigh the risks before transplant
Despite the possible short-term problems and those that can crop up after a while, stem cell transplant has been used to cure thousands of people with otherwise deadly cancers. Still, the possible risks and complications can threaten life, too.
The expected risks and benefits must be weighed carefully before transplant. Research today is being done to not only to cure cancer, but also to improve transplant methods and reduce the risks.
Sources of stem cells for transplant
There are 3 possible sources of stem cells to use for transplants:
- Bone marrow (from you or someone else)
- The bloodstream (peripheral blood – from you or someone else)
- Umbilical cord blood from newborns
Bone marrow is the spongy tissue in the center of some bones. Its main job is to make blood cells that circulate in your body, which includes immune cells that recognize invaders and fight infection.
Bone marrow has a rich supply of stem cells. The bones of the pelvis (hip) contain the most marrow and have large numbers of stem cells in them.
For this reason, cells from the pelvic bone are used most often for a bone marrow transplant. Enough marrow must be removed to collect a large number of healthy stem cells.
When the bone marrow is removed (harvested), the donor gets general anesthesia (drugs are used to put the patient into a deep sleep so they don’t feel pain).
A large needle is put through the skin and into the back of the hip bone. The thick liquid marrow is pulled out through the needle.
This is repeated several times until enough marrow has been taken out or harvested. (For more on this, see the section called “What’s it like to donate stem cells?”)
The harvested marrow is filtered, stored in a special solution in bags, and then frozen. When the marrow is to be used, it’s thawed and then given into the vein just like a blood transfusion.
The stem cells travel to the recipient’s bone marrow.
Over time, they engraft or “take” and begin to make blood cells. Signs of the new blood cells usually can be measured in the patient’s blood tests in about 2 to 4 weeks.
Normally, few stem cells are found in the blood. But giving hormone-like substances called growth factors to stem cell donors a few days before the harvest causes their stem cells to grow faster and move from the bone marrow into the blood.
For a peripheral blood stem cell transplant, the stem cells are taken from blood. A special thin flexible tube (called a catheter) is put into a large vein in the donor and attached to tubing that carries the blood to a special machine.
The machine separates the stem cells from the rest of the blood, which is given back to the donor during the same procedure.
This takes several hours, and may need to be repeated for a few days to get enough stem cells. The stem cells are filtered, stored in bags, and frozen until the patient is ready for them. (For more on this, see the section called “What’s it like to donate stem cells?”)
After the patient is treated with chemotherapy and/or radiation, the stem cells are infused into the vein, much like a blood transfusion.
The stem cells travel to the bone marrow, engraft, and then start making new, normal blood cells. The new cells are usually found in the patient’s blood a few days sooner than when bone marrow stem cells are used, usually in about 10 to 20 days.
Umbilical cord blood
Not everyone who needs an allogeneic stem cell transplant can find a well-matched donor among family members or among the people who have signed up to donate.
For these patients, umbilical cord blood may be a source of stem cells. About 1 in 3 unrelated hematopoietic stem cell transplants are done with cord blood.
A large number of stem cells are normally found in the blood of newborn babies. After birth, the blood that is left behind in the placenta and umbilical cord (known as cord blood) can be taken and stored for later use in a stem cell transplant.
The cord blood is frozen until needed. A cord blood transplant uses blood that normally is thrown out after a baby is born.
The first cord blood transplant was done in 1988, and its use has been growing ever since. For more information on donating cord blood, see the section called “What’s it like to donate stem cells?”
A possible drawback of cord blood is the smaller number of stem cells present. But this is partly balanced by the fact that each cord blood stem cell can form more blood cells than a stem cell from adult bone marrow.
Still, cord blood transplants can take longer to take hold and start working.
To be safe, most cord blood transplants done so far have been in children and smaller adults. Researchers are now looking for ways to use cord blood for transplants in larger adults.
One approach that is being taken is to find ways to increase the numbers of these cells in the lab before the transplant.
Another approach is the use of the cord blood from 2 infants at the same time for one adult transplant, called a dual-cord-blood transplant.
A third way cord blood is being used is in a mini-transplant. In this case, the bone marrow is not completely destroyed so there are some host stem cells left before and during the time that the cord blood stem cells engraft.
Other strategies to better use cord blood transplants are being actively studied.
Which stem cell source is best?
All 3 sources of stem cells can be used for the same goal: to give the patient healthy stem cells that will mature into healthy blood cells.
There are pros and cons to each source, but all are usually able to provide the needed number of stem cells (with the exception noted above in umbilical cord blood).
When stem cell transplants were first used, they were all bone marrow transplants. But today peripheral blood stem cell transplants are much more common.
Often, doctors are able to harvest more stem cells from peripheral blood than from bone marrow
. It’s also easier for donors to give peripheral blood stem cells than bone marrow, although it takes longer. Another plus for peripheral blood stem cell transplants is that the recipient’s blood count often recovers faster than with a bone marrow transplant.
But the risk of chronic graft-versus-host disease is somewhat higher with peripheral blood stem cell transplants than with bone marrow transplants.
Cord blood transplant may be an option if a good match can’t be found among volunteer stem cell donors. Even though well-matched cord blood is generally best, studies suggest that cord blood doesn’t have to be as closely matched as bone marrow or peripheral blood.
This may be an advantage for patients with rare tissue types. This type of transplant also does not require a separate donation procedure and may reduce the risk and severity of graft-versus-host disease (described in the section called “Problems that may come up shortly after transplant”).
But cord blood cells usually take longer to engraft. This leaves the patient at high risk for infection and bleeding longer than is seen with transplanted marrow or peripheral blood stem cells.
Another drawback is that, unlike bone marrow transplant or peripheral blood stem cell transplant, the donor cannot be called back for more after the cord blood stem cells are used.
Donor matching for allogeneic transplant
The immune system normally keeps us healthy by destroying anything in the body it sees as foreign, such as bacteria or viruses.
A working immune system recognizes cells from other people as foreign, too. This becomes very important in an allogeneic stem cell transplant.
If the tissue type match between donor and recipient is not close, the patient’s immune system may see the new stem cells as foreign and destroy them.
This is called graft rejection, and it can lead to graft failure. This is rare when the donor and recipient are well matched.
A more common problem is that when the donor stem cells make their own immune cells, the new cells may see the patient’s cells as foreign and turn against their new home.
This type of attack is called graft-versus-host disease. (See “Graft-versus-host disease” in the section called “Problems that may come up shortly after transplant” for details). The grafted stem cells attack the body of the person who got the transplant. This is another reason it’s so important to find the closest match possible.
The transplant process
There are several steps in the transplant process. The steps are much the same, no matter what type of transplant you are going to have.
Evaluation and preparation for a transplant
You will first be evaluated to find out if you are eligible for a transplant. A transplant is very hard on your body. For many people, transplants can mean a cure, but complications can lead to death in some cases.
You will want to weigh the pros and cons before you start.
Transplants can be hard emotionally, too. They often require being in the hospital, being isolated, and there is a high risk of side effects.
Many of the effects are short-term, but some problems can go on for years. This can mean changes in the way you live your life. For some people it’s just for a while, but for others the changes may be lifelong.
It’s also very hard going through weeks and months of not knowing how your transplant will turn out. This takes a lot of time and emotional energy from the patient, caregivers, and loved ones. It’s very important to have the support of those close to you.
You will need, for instance, a responsible adult who will be with you to give you medicines, help watch for problems, and stay in touch with the team after you go home.
Your transplant team will help you and your caregiver learn what you need to know. The team can also help you and your loved ones work through the ups and downs as you prepare for and go through the transplant.
Many different medical tests may be done, and questions will be asked to try to find out how well you can handle the transplant process. These might include:
- HLA tissue typing, including high-resolution typing
- A complete health history and physical exam
- Evaluation of your psychological and emotional strengths
- Identifying who will be your primary caregiver throughout the transplant process
- Bone marrow biopsy
- CT (computed tomography) scan or MRI (magnetic resonance imaging)
- Heart tests, such as an EKG (electrocardiogram) or echocardiogram
- Lung studies, such as a chest x-ray and PFTs (pulmonary function tests)
- Consultations with other members of the transplant team, such as a dentist, dietitian, or social worker
- Blood tests, such as a complete blood count, blood chemistries, and screening for viruses like hepatitis B, CMV, and HIV
You will also talk about your health insurance coverage and related costs that you might have to pay.
You may have a central venous catheter (thin tube) put into a large vein in your chest. This is most often done as outpatient surgery, and usually only local anesthesia is needed (the place where the catheter goes in is made numb).
Nurses will use the catheter to draw blood and give you medicines.
If you are getting an autologous transplant, a special catheter can be placed that can also be used for apheresis (a-fur-REE-sis) to harvest your stem cells.
The catheter will stay in during your treatment and for some time afterward, usually until your transplanted stem cells have engrafted and your blood counts are on a steady climb to normal.
Younger people, those who are in the early stages of disease, or those who have not already had a lot of treatment, often do better with transplants.
Some transplant centers set age limits. For instance, they may not allow regular allogeneic transplants for people over 50 or autologous transplants for people over 60 or 65.
Some people also may not be eligible for transplant if they have other major health problems, such as serious heart, lung, liver, or kidney disease.
A mini-transplant, described under “Allogeneic stem cell transplant” in the section called “Types of stem cell transplants for treating cancer” may be an option for some of these patients.
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 will 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 get you 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 admitted to 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 are going to be treated as an outpatient or at home, 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 is no going back — there can be serious problems if treatment is stopped at any time during transplant.
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 all of the cancer cells anywhere in the patient’s body
- The conditioning treatment is different for every transplant. Your individual treatment will be planned based on the type of cancer you have, the type of transplant, and any chemo or radiation therapy you have had in the past.
If chemo is part of your treatment plan, it will be given in an intravenous (IV) line or as pills. If radiation therapy is planned, it’s given to the entire body (called total body irradiation or TBI).
TBI 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 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.
If you know what medicines your doctors will be using for conditioning, you can find out more about them in our Guide to Cancer Drugs, or call us for more information.
Conditioning can also cause premature menopause in women and often makes both men and women sterile (unable to have children).
Before you have a transplant, you need to discuss the transplant process and all its effects with your doctors. It also helps to talk to others who have already had transplants.
The big day: infusion of stem cells
After the conditioning treatment, you will be given a couple of days to rest before getting the stem cells. They will be given through your IV catheter, much like a blood transfusion.
If the stem cells were frozen, you might get some drugs before the stem cells are given. This is done to reduce your risk of reacting to the preservatives that are used in freezing the cells.
If the stem cells were frozen, they are thawed in warm water then given right away.
For allogeneic or syngeneic transplants, the donor cells may be harvested (removed) in an operating room, and then processed in the lab. Once they are ready, the cells are brought in and infused (given to you).
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 are rare and usually mild. The preserving agent used when freezing the cells (called dimethylsulfoxide or DMSO) causes many of the side effects. 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 short-term or immediate side effects of the stem cell infusion might include:
- Fever or chills
- Shortness of breath
- Tightness in the chest
- Low blood pressure
- 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.
Recovery after infusion
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 begin 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 will 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 given until the bone marrow is working again 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 gastrointestinal (GI) or stomach problems, and heart, lung, liver or kidney problems.
(We will talk more about these later, in the section called “Problems that may come up shortly after transplant.”) 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.
Having a transplant is a big decision. Your life and your relationships will be disrupted. Your future becomes uncertain, the process makes you feel bad, and financially it can be overwhelming.
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 of 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 will need to take
- 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 professionals
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
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 (see the section called “What are stem cells and why are they transplanted?” for more information about neutrophils, platelets, and hematocrit):
- They have no fever for 48 hours
- They are able to take and keep down pills or other drugs for 48 hours
- Their nausea, vomiting, and diarrhea are controlled with medicine
- Their neutrophil count (absolute neutrophil count or ANC) is at least 500 to 1,000/mm3
- They have a hematocrit of at least 25% to 30%
- They have a platelet count of at least 15,000 to 20,000/mm3
- They have someone to help them at home and a safe and supportive home environment
If patients do not meet all of these requirements, but still don’t need the intensive care of the transplant unit, they may be moved another oncology unit.
When you do go home, you may need to stay near the transplant center for some time, depending on your condition.
The roller coaster ride typically continues after you go home. Plus, you will be feeling pretty tired after going through the transplant process.
After discharge, some people have physical or mental health problems in the rehabilitation period. These ongoing needs must now be managed at home and caregiver and friend/family support is very important.
Transplant patients are still followed closely during rehab. You may need daily or weekly exams along with things like blood tests, chest x-rays, bone marrow tests, or spinal taps (lumbar punctures).
During early rehab, you also might need blood and platelet transfusions, antibiotics, or other treatments. The exams are frequent at first, maybe even every day, but will be needed less often 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.
Some problems might show up as much as a year or more after the stem cells are infused. Physical problems are usually from the chemo and/or radiation treatment, but other issues may pop up too. Problems can include:
- Graft-versus-host disease (in allogeneic transplants)
- 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
- 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
- Slowed growth and development (in children)
- Reproductive or sexual problems, like infertility, early menopause, pain or discomfort during sex, or loss of interest in sex (see “Stem cell transplant and having children” in the section “Transplant problems that may show up later”)
New cancers caused by the transplant
Your transplant team is still available 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.