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In a typical stem cell transplant for cancer very high doses of chemo are used, sometimes along with radiation therapy, to try to kill all the cancer cells. This treatment also kills the stem cells in the bone marrow. Soon after treatment, stem cells are given to replace those that were destroyed. These stem cells are given into a vein, much like a blood transfusion. Over time they settle in the bone marrow and begin to grow and make healthy blood cells. This process is called engraftment.
There are 2 main types of transplants. They are named based on who gives the stem cells.
In this type of transplant, your own stem cells are removed, or harvested, from your blood before you get treatment that destroys them. Your stem cells are removed from either your bone marrow or your blood, and then frozen. (You can learn more about this process at What’s It Like to Donate Stem Cells?) After you get high doses of chemo and/or radiation, the stem cells are thawed and given back to you.
One advantage of autologous stem cell transplant is that you’re getting your own cells back. You don’t have to worry about the new stem cells (called the engrafted cells or the “graft”) attacking your body (graft-versus-host disease) or about getting a new infection from another person. But there can still be graft failure, which means the cells don’t go into the bone marrow and make blood cells like they should. Also, autologous transplants can’t produce the “graft-versus-cancer” effect.
This kind of transplant is mainly used to treat certain leukemias, lymphomas, and multiple myeloma. It’s sometimes used for other cancers, like testicular cancer and neuroblastoma, and certain cancers in children. Doctors are looking at how autologous transplants might be used to treat other diseases, too, like systemic sclerosis, multiple sclerosis (MS), Crohn’s disease, and systemic lupus erythematosis (lupus).
A possible disadvantage of an autologous transplant is that cancer cells may be collected along with the stem cells and then later put back into your body. Another disadvantage is that your immune system is the same as it was before your transplant. This means the cancer cells were able to escape attack from your immune system before, and may be able to do so again.
To help prevent this, some centers treat the stem cells before they’re given back to the patient to try to kill any remaining cancer cells. This may be called purging. It isn’t clear that this really helps, as it has not yet been proven to reduce the risk of cancer coming back. A possible downside of purging is that some normal stem cells can be lost during this process. This may cause your body to take longer to start making normal blood cells, and you might have very low and unsafe levels of white blood cells or platelets for a longer time. This could increase the risk of infections or bleeding problems.
Another treatment to help kill cancer cells that might be in the returned stem cells involves giving anti-cancer drugs after transplant. The stem cells are not treated. After transplant, the patient gets anti-cancer drugs to get rid of any cancer cells that may be in the body. This is called in vivo purging. For instance, rituximab (Rituxan®), a monoclonal antibody drug, may be used this way in certain lymphomas and leukemias; lenalidomide (Revlimid®) may be used for multiple myeloma. The need to remove cancer cells from transplanted stem cells or transplant patients and the best way to do it is being researched.
Doing 2 autologous transplants in a row is known as a tandem transplant or a double autologous transplant. In this type of transplant, the patient gets 2 courses of high-dose chemo, each followed by a transplant of their own stem cells. All of the stem cells needed are collected before the first high-dose chemo treatment, and half of them are used for each transplant. Usually, the 2 courses of chemo are given within 6 months. The second one is given after the patient recovers from the first one.
Tandem transplants are most often used to treat multiple myeloma and advanced testicular cancer. But doctors don’t always agree that these are really better than a single transplant for certain cancers. Because this involves 2 transplants, the risk of serious outcomes is higher than for a single transplant. Tandem transplants are still being studied to find out when they might be best used.
Sometimes an autologous transplant followed by an allogeneic transplant might also be called a tandem transplant. (See “Mini-transplants” below.)
Allogeneic stem cell transplants use cells from a donor. In the most common type of allogeneic transplant, the stem cells come from a donor whose tissue type closely matches the patient’s. (This is discussed later in “Matching patients and donors.”) The best donor is a close family member, usually a brother or sister. If you don’t have a good match in your family, a donor might be found in the general public through a national registry. This is sometimes called a MUD (matched unrelated donor) transplant. Transplants with a MUD are usually riskier than those with a relative who is a good match.
Blood taken from the placenta and umbilical cord of newborns is a newer source of stem cells for allogeneic transplant. Called cord blood, this small volume of blood has a high number of stem cells that tend to multiply quickly. But there are often not enough stem cells in a unit of cord blood for large adults, so 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 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 for one adult transplant, called a dual-cord-blood transplant. A third way cord blood is being used is in a mini-transplant (see below). Other strategies to better use cord blood transplants are being actively studied.
Pros of allogeneic stem cell transplant: The donor stem cells make their own immune cells, which could help kill any cancer cells that remain after high-dose treatment. This is called the graft-versus-cancer effect. Other advantages are that the donor can often be asked to donate more stem cells or even white blood cells if needed, and stem cells from healthy donors are free of cancer cells.
Cons to allogeneic stem cell transplants: The transplant, or graft, might not take – that is, the transplanted donor stem cells could die or be destroyed by the patient’s body before settling in the bone marrow. Another risk is that the immune cells from the donor may not just attack the cancer cells – they could attack healthy cells in the patient’s body. This is called graft-versus-host disease. There is also a very small risk of certain infections from the donor cells, even though donors are tested before they donate. A higher risk comes from infections you had previously, and which your immune system has had under control. These infections may surface after allogeneic transplant because your immune system is held in check (suppressed) by medicines called immunosuppressive drugs. Such infections can cause serious problems and even death.
Allogeneic transplant is most often used to treat certain types of leukemia, lymphomas, multiple myeloma, myelodysplastic syndrome, and other bone marrow disorders such as aplastic anemia.
For some people, age or certain health conditions make it more risky to wipe out all of their bone marrow before a transplant. For those people, doctors can use a type of allogeneic transplant that’s sometimes called a mini-transplant. Your doctor might refer to it as a non-myeloablative transplant or mention reduced-intensity conditioning (RIC). Patients getting a mini transplant get less chemo and/or radiation than if they were getting a standard transplant. The goal is to kill some of the cancer cells (which will also kill some of the bone marrow), and suppress the immune system just enough to allow donor stem cells to settle in the bone marrow.
Unlike the standard allogeneic transplant, cells from both the donor and the patient exist together in the patient’s body for some time after a mini-transplant. But slowly, over the course of months, the donor cells take over the bone marrow and replace the patient’s own bone marrow cells. These new cells can then develop an immune response to the cancer and help kill off the patient’s cancer cells – the graft-versus-cancer effect.
One advantage of a mini-transplant is that it uses lower doses of chemo and/or radiation. And because the stem cells aren’t all killed, blood cell counts don’t drop as low while waiting for the new stem cells to start making normal blood cells. This makes it especially useful for older patients and those with other health problems. Rarely, it may be used in patients who have already had a transplant.
Mini-transplants treat some diseases better than others. They may not work well for patients with a lot of cancer in their body or people with fast-growing cancers. Also, although side effects from chemo and radiation may be less than those from a standard allogeneic transplant, the risk of graft-versus-host disease is the same.
This procedure has only been used since the late 1990s and long-term patient outcomes are not yet clear. There are lower risks of some complications, but the cancer may be more likely to come back. Ways to improve outcomes are still being studied.
Studies have looked at using an allogeneic mini-transplant after an autologous transplant. This is another type of tandem transplant being tested in certain types of cancer, such as multiple myeloma and some types of lymphoma. The autologous transplant can help decrease the amount of cancer present so that the lower doses of chemo given before the mini-transplant can work better. And the recipient still gets the benefit of the graft-versus-cancer effect of the allogeneic transplant.
This is a special kind of allogeneic transplant that can only be used when the patient has an identical sibling (twin or triplet) – someone who has the exact same tissue type. An advantage of syngeneic stem cell transplant is that graft-versus-host disease will not be a problem. Also, there are no cancer cells in the transplanted stem cells, as there might be in an autologous transplant.
A disadvantage is that because the new immune system is so much like the recipient’s immune system, there’s no graft-versus-cancer effect. Every effort must be made to destroy all the cancer cells before the transplant is done to help keep the cancer from coming back.
Some centers are doing half-match (haploidentical) transplants for people who don’t have closely matching family members. This technique is most often used in children, usually with a parent as the donor, though a child can also donate to a parent. Half of the HLA factors will match perfectly, and the other half typically don’t match at all, so the procedure requires a special way to get rid of a certain white blood cells that can cause graft-versus-host disease. It’s still rarely done, but it’s being studied in a few centers in the US. Researchers are continuing to learn new ways to make haploidentical transplants more successful.
Depending on the type of transplant that’s done, there are 3 possible sources of stem cells to use for transplants:
Bone marrow is the spongy liquid tissue in the center of some bones. It has a rich supply of stem cells, and its main job is to make blood cells that circulate in your body. The bones of the pelvis (hip) have the most marrow and contain large numbers of stem cells. 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.
The bone marrow is harvested (removed) while the donor is under 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 on the lower back and into the back of the hip bone. The thick liquid marrow is pulled out through the needle. This is repeated until enough marrow has been taken out. (For more on this, see 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 put into the patient’s blood through a vein, just like a blood transfusion. The stem cells travel to the bone marrow, where they engraft or “take” and start 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, not many stem cells are found in the blood. But giving shots of 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 returned 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 What’s It Like to Donate Stem Cells?)
When they’re given to the patient, the stem cells are put into a 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 in about 10 to 20 days.
A large number of stem cells are normally found in the blood of newborn babies. After birth, the blood that’s 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. More information on donating cord blood can be found in What’s It Like to Donate Stem Cells?
A possible drawback of cord blood is the smaller number of stem cells in it. 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. Cord blood is given into the patient’s blood just like a blood transfusion.
It is very important that the donor and recipient are a close tissue match to avoid graft rejection. Graft rejection happens when the recipient’s immune system recognizes the donor cells as foreign and tries to destroy them as it would a bacteria or virus. Graft rejection can lead to graft failure, but it’s 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 attack their new “home.” This is called graft-versus-host disease. (See Stem Cell Transplant Side Effects for more on this). The new, 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.
Many factors play a role in how the immune system knows the difference between self and non-self, but the most important for transplants is the human leukocyte antigen (HLA) system. Human leukocyte antigens are proteins found on the surface of most cells. They make up a person’s tissue type, which is different from a person’s blood type.
Each person has a number of pairs of HLA antigens. We inherit them from both of our parents and, in turn, and pass them on to our children. Doctors try to match these antigens when finding a donor for a person getting a stem cell transplant.
How well the donor’s and recipient’s HLA tissue types match plays a large part in whether the transplant will work. A match is best when all 6 of the known major HLA antigens are the same – a 6 out of 6 match. People with these matches have a lower chance of graft-versus-host disease, graft rejection, having a weak immune system, and getting serious infections. For bone marrow and peripheral blood stem cell transplants, sometimes a donor with a single mismatched antigen is used – a 5 out of 6 match. For cord blood transplants a perfect HLA match doesn’t seem to be as important, and even a sample with a couple of mismatched antigens may be OK.
Doctors keep learning more about better ways to match donors. Today, fewer tests may be needed for siblings, since their cells vary less than an unrelated donor. But to reduce the risks of mismatched types between unrelated donors, more than the basic 6 HLA antigens may be tested. For example, sometimes doctors to try and get a 10 out of 10 match. Certain transplant centers now require high-resolution matching, which looks more deeply into tissue types and allow more specific HLA matching.
There are thousands of different combinations of possible HLA tissue types. This can make it hard to find an exact match. HLA antigens are inherited from both parents. If possible, the search for a donor usually starts with the patient’s brothers and sisters (siblings), who have the same parents as the patient. The chance that any one sibling would be a perfect match (that is, that you both received the same set of HLA antigens from each of your parents) is 1 out of 4.
If a sibling is not a good match, the search could then move on to relatives who are less likely to be a good match – parents, half-siblings, and extended family, such as aunts, uncles, or cousins. (Spouses are no more likely to be good matches than other people who are not related.) If no relatives are found to be a close match, the transplant team will widen the search to the general public.
As unlikely as it seems, it’s possible to find a good match with a stranger. To help with this process, the team will use transplant registries, like those listed here. Registries serve as matchmakers between patients and volunteer donors. They can search for and access millions of possible donors and hundreds of thousands of cord blood units.
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