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December 27th, 2024

Types of Stem Cell and Bone Marrow Transplants

By daniellenierenberg

Stem cell transplants are used to put blood stem cells back into the body after the bone marrow has been destroyed by disease, chemotherapy (chemo), or radiation. Depending on where the stem cells come from, the transplant procedure may go by different names:

All of these can also be calledhematopoietic stem cell transplants.

In a typical stem cell transplant for cancer, a person first gets very high doses of chemo, sometimes along with radiation therapy, to try to kill all the cancer cells. This treatment also kills the stem cells in the bone marrow. This is called myeloablation or myeloablative therapy.

Soon after treatment, blood stem cells are given (transplanted) to replace those that were destroyed. The replacement stem cells are given into a vein, much like ablood transfusion. The goal is that over time, the transplanted cells will settle in the bone marrow, where they will begin to grow and make healthy new blood cells. This process is called engraftment.

There are 2 main types of transplants. They are named based on who donates the stem cells.

In this type of transplant, the first step is to remove or harvest your own stem cells. Your stem cells are removed from either your bone marrow or your blood, and then frozen. (You can learn more about this process at Whats It Like to Donate Stem Cells?) After you get high doses of chemo and/or radiation as your myeloablative therapy, the stem cells are thawed and given back to you.

This kind of transplant is mainly used to treat certain leukemias, lymphomas, and multiple myeloma. Its sometimes used for other cancers, like testicular cancer and neuroblastoma, and certain cancers in children. Doctors can use autologous transplants for other diseases, too, like systemic sclerosis, multiple sclerosis (MS), Crohn's disease, and systemic lupus erythematosus (lupus).

An advantage of an autologous stem cell transplantis that youre getting your own cells back. When you get your own stem cells back, you dont have to worry about them (called the engrafted cells or the graft) being rejected by your body. You also dont have to worry about immune cells from the transplant attacking healthy cells in your body (known as graft-versus-host disease), which is a concern with allogeneic transplants.

An autologous transplant graft might still fail, which means the transplanted stem cells dont go into the bone marrow and make blood cells like they should.

Also, autologous transplants cant produce the graft-versus-cancer effect, in which the donor immune cells from the transplant help kill any cancer cells that remain.

Another possible disadvantage of an autologous transplant is that cancer cells might be collected along with the stem cells and then later be put back into your body.

To help prevent any remaining cancer cells from being transplanted along with stem cells, some centers treat the stem cells before theyre given back to the patient. This may be called purging. While this might work for some patients, there haven't been enough studies yet to know if this is really a benefit. 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 the 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, lenalidomide (Revlimid) may be used in this way for multiple myeloma. The need to remove cancer cells from transplanted stem cells or transplant patients and the best way to do it continues to be 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 as myeloablative therapy, 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 have become the standard of care for certain cancers. High-risk types of the childhood cancer neuroblastoma and adult multiple myeloma are cancers where tandem transplants seem to show good results. But doctors dont always agree that these are really better than a single transplant for certain cancers. Because this treatment involves 2 transplants, the risk of serious outcomes is higher than for a single transplant.

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 donor stem cells. In the most common type of allogeneic transplant, the stem cells come from a donor whose tissue type closely matches yours. (This is discussed in Matching patients and donors.) The best donor is a close family member, usually a brother or sister. If you dont 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.

An allogeneic transplant works about the same way as an autologous transplant. Stem cells are collected from the donor and stored or frozen. After you get high doses of chemo and/or radiation as your myeloablative therapy, the donor's stem cells are thawed and given to you.

Allogeneic transplants are most often used to treat certain types of leukemia, lymphomas, multiple myeloma, myelodysplastic syndromes, and other bone marrow disorders such as aplastic anemia.

Blood taken from the placenta and umbilical cord after a baby is born can also be used for an allogeneic transplant. This small volume of cord blood has a high number of stem cells in it.

Cord blood transplants can have some advantages. For example, there are already a large number of donated units in cord blood banks, so finding a donor match might be easier. These units have already been donated, so they dont need to be collected once a match is found. A cord blood transplant is also less likely to be rejected by your body than is a transplant from an adult donor.

But cord blood transplants can have some downsides as well. There arent as many stem cells in a cord blood unit as there are in a typical transplant from an adult donor. Because of this, cord blood transplants are used more often for children, who have smaller body sizes. These transplants can be used for adults as well, although sometimes a person might need to get more than one cord blood unit to help ensure there are enough stem cells for the transplant.

Cord blood transplants can also take longer to begin making new blood cells, during which time a person is vulnerable to infections and other problems caused by having low blood cell counts. For a newer cord blood product, known as omidubicel (Omisirge), the cord blood cells are treated in a lab with a special chemical, which helps them get to the bone marrow and start making new blood cells quicker once theyre in the body.

A major benefit of allogeneic transplants is that 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 or graft-versus-tumor effect.

Other advantages are that the donor can often be asked to donate more stem cells or even white blood cells if needed (although this isn't true for a cord blood transplant), and stem cells from healthy donors are free of cancer cells.

As with any type of transplant, there is a risk that the transplant, or graft, might not take that is, the transplanted donor stem cells could die or be destroyed by the patients body before settling in the bone marrow.

Another risk is that the immune cells from the donor could attack healthy cells in the patients body. This is called graft-versus-host disease, and it can range from mild to life-threatening.

There is also a very small risk of certain infections from the donor cells, even though donors are tested before they donate.

Another risk is that some types of infections you had previously and which your immune system has had under control may resurface after an allogeneic transplant. This can happen when your immune system is weakened (suppressed) by medicines called immunosuppressive drugs. Such infections can cause serious problems and can even be life-threatening.

For some people, age or certain health conditions make it more risky to do myeloablative therapy that wipes out all of their bone marrow before a transplant. For those people, doctors can use a type of allogeneic transplant thats 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 typically get lower doses of chemo and/or radiation than if they were getting a standard myeloablative transplant. The goal in the mini-transplant 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 patients 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 patients own bone marrow cells. These new cells can then develop an immune response to the cancer and help kill off the patients 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 arent all killed, blood cell counts dont 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 there might be fewer side effects from chemo and radiation than those from a standard allogeneic transplant, the risk of graft-versus-host disease is the same. Some studies have shown that for some cancers and some other blood conditions, both adults and children can have the same kinds of results with a mini-transplant as compared to a standard 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 recipients immune system, theres 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.

Improvements have been made in the use of family members as donors. This kind of transplant is called ahalf-match (haploidentical) transplant for people who dont have fully matching or identical family member. This can be another option to consider, along with cord blood transplant and matched unrelated donor (MUD) transplant.

If possible, it is very important that the donor and recipient are a close tissue match to avoid graft rejection. Graft rejection happens when the recipients 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 its 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 patients 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 its 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 persons tissue type, which is different from a persons blood type.

Each person has a number of pairs of HLA antigens. We inherit them from both of our parents and, in turn, 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 donors and recipients 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 doesnt 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 patients 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, its 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.

Be the Match (formerly the National Marrow Donor Program)Toll-free number: 1-800-MARROW-2 (1-800-627-7692)Website: http://www.bethematch.org

Blood & Marrow Transplant Information NetworkToll-free number: 1-888-597-7674Website: http://www.bmtinfonet.org

Depending on a persons tissue typing, several other international registries also are available. Sometimes the best matches are found in people with a similar racial or ethnic background. When compared to other ethnic groups, white people have a better chance of finding a perfect match for stem cell transplant among unrelated donors. This is because ethnic groups have differing HLA types, and in the past there was less diversity in donor registries, or fewer non-White donors. However, the chances of finding an unrelated donor match improve each year, as more volunteers become aware of registries and sign up for them.

Finding an unrelated donor can take months, though cord blood may be a little faster. A single match can require going through millions of records. Also, now that transplant centers are more often using high-resolution tests, matching is becoming more complex. Perfect 10 out of 10 matches at that level are much harder to find. But transplant teams are also getting better at figuring out what kinds of mismatches can be tolerated in which particular situations that is, which mismatched antigens are less likely to affect transplant success and survival.

Keep in mind that there are stages to this process there may be several matches that look promising but dont work out as hoped. The team and registry will keep looking for the best possible match for you. If your team finds an adult donor through a transplant registry, the registry will contact the donor to set up the final testing and donation. If your team finds matching cord blood, the registry will have the cord blood sent to your transplant center.

Originally posted here:
Types of Stem Cell and Bone Marrow Transplants

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December 27th, 2024

Explained: What is mesenchymal stem cell therapy? – Drug Discovery News

By daniellenierenberg

Explained: What is mesenchymal stem cell therapy? Drug Discovery News

Ossium CEO and cofounder Kevin Caldwell.

Unlike a solid organ, you cant just transplant bone marrow into the nearest person who is roughly the right size who needs it, Caldwell says. You really have to have a close genetic match between the donor and the recipient.

The new method of stem cell harvesting, via apheresis, doesnt work well in deceased people because it relies on blood pressure. Based on previous research conducted at the University of Pittsburgh and Johns Hopkins University, Ossium developed a way to extract bone marrow from the spinal column, a part of the body that typically went unused. The company has partnered with US organ procurement organizations to recover spinal columns from cadavers and ship them to the companys facility in Indianapolis. There, bone marrow is extracted and cryopreserved in liquid nitrogen vapor at about 190 degrees Celsius.

Caldwell says Ossium has processed thousands of donors since the company was founded in 2016. (The exact number of donors in the bank is proprietary, he says.) Ossiums frozen bone marrow has now been given to three people in total, including the Michigan woman, with a fourth transplant scheduled soon.

Robert Negrin, a professor of medicine at Stanford University and vice president of the American Society of Hematology, calls the transplants an important milestone, but whether the technique will be useful for cancer patients remains to be seen. We have other options that work pretty well, he says, referring to partially matched donor transplants and cord blood transplants. But there are always situations that could fall through the cracks.

Negrin sees potential for deceased donor bone marrow transplants to help organ transplant patients, who currently must take immunosuppressive drugs for the rest of their lives to avoid their immune system attacking the new organ. But because immune cells originate in the bone marrow, if they could receive a marrow transplant from the same donor, Negrin says patients couldin theorygo off immunosuppressive drugs.

Link:
Bone Marrow Donors Can Be Hard to Find. One Company Is Turning to ...

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November 15th, 2024

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