What does allogeneic mean?

Allogeneic means taken from someone else.

What is bone marrow and stem cells?

Bone marrow is a spongy material found inside our large bones, like the femur (thigh), hip, and ribs. Bone marrow is made up of cells called hematopoietic stem cells. There are also cells found in your bloodstream called peripheral blood stem cells. These stem cells are different than those used for research - those are embryonic stem cells.

Hematopoietic stem cells are "baby" cells that become white blood cells, red blood cells, or platelets. They can be called blood-forming stem cells. They grow and are stored in the bone marrow until they are needed. Each type of cell has a job:

White blood cells (leukocytes): Cells that help fight infection.
Red blood cells (erythrocytes): Carry oxygen from the lungs to the rest of the body and return carbon dioxide to the lungs as waste.
Platelets (thrombocytes): Help the body form blood clots to control bleeding.

What is an allogeneic transplant?

An allogeneic transplant is when bone marrow or stem cells from another person (donor) are put into your body. The donor may be a sibling, relative, or someone unrelated to you (these cells can even come from umbilical cord blood). If the cells come from your identical twin, the transplant is called syngeneic and is very much like an autologous transplant, because the cells are identical to yours.

Allogeneic transplants are used to treat many different cancers such as leukemias, lymphomas, multiple myeloma, severe aplastic anemia, and sickle cell disease, among others. (See the complete list from the National Marrow Donor Program)

How is a donor chosen?

The donated cells must be "matched" to you, which is done by a test called human leukocyte antigen (HLA) or HLA typing.

About 7 out of 10 patients will not have a family member match and will need to use the National Marrow Donor Program. They keep the HLA typing records from donors around the world and have access to millions of potential donors and numerous cord blood units. If a patient has a donor that is unrelated to them it is often called MUD (matched unrelated donor).

How is HLA testing done?

The match is "scored" based on the number of markers that match between the patient and donor’s typing. The higher the number of matching HLA antigens, the better the match and the greater the chance that the patient's body will accept the donor's stem cells.

The HLA type is made up of either 8 or 10 HLA markers. Half are inherited from the mother and half are inherited from the father. There are 2 of each of the markers, called A, B, C, DRB1, and DQ (which is not always used).

Providers usually look first to a family member for a match. Siblings from the same parents have a 25% chance of being an identical match (all markers match, called an 8 out of 8 or 10 out of 10 match). If your sibling matches half of your HLA markers, it is called a haploidentical match (4 out of 8). If no siblings match, the patient's parents or children can be tested.

In cord blood transplants, a well-matched donor seems to be less important. These cells are matched using 6 antigens (A, B, and DRB1), and a 4 out of 6 match is acceptable.

What steps will the donor take before the transplant?

The donor’s cells will be collected by using a medication called granulocyte colony-stimulating factor, or GCSF. This medicine stimulates (revs up) the stem cells to be released from the bone marrow and into the bloodstream. Using a blood test, they can tell how many cells are in the bloodstream. Once the number is high enough, the donor will go to the area of the hospital where pheresis is done to have the cells taken out. This procedure is called "apheresis.” With apheresis, there is no longer a need to remove stem cells from bone marrow. This is how apheresis works:

The donor’s cells are taken out using a catheter in the chest wall, or with 2 large intravenous (IV) catheters, one placed in each arm.
Blood is taken out, run through the pheresis machine to remove the stem cells, and the rest of the blood is returned to the donor.
The cells are frozen in the same dimethyl sulfoxide (DMSO) preservative that is used for bone marrow. Preserving the cells on ice, called “cryopreservation,” is needed because the cells must be removed (“harvested”) months before the transplant.
During the collection, the donor may have tingling or numbness around their lips. This is caused by a loss of calcium and often gets better by eating some calcium tablets.
The donor may also have hand cramping which is caused by the blood-thinning agent used during collection. This will go away when the collection is done.

The whole collection takes 3-4 hours.

The donated cells can also be taken from umbilical cord blood. The umbilical cord is often thrown away after a baby is born. The blood in the cord is rich in hematopoietic stem cells that can be used in allogeneic transplants. Cord blood is most often used in children and smaller-sized adults. Cord blood can take longer to engraft (see more on engraftment below) and may lead to an increased risk of infection.

What steps will the patient take before the transplant?

You may also hear these steps called the “preparative regimen”. In the days before your transplant, you will get high doses of chemotherapy and in some cases radiation. These steps are taken to prepare your body to receive the donor’s cells. Chemotherapy is given for a few reasons:

To destroy your marrow and immune system so that it does not attack the donor's cells.
To destroy any cancer cells still in your body.

There are two types of preparative regimens and they have to do with the amount of chemotherapy and/or radiation you are getting. The regimens are called:

Myeloablative (also called standard intensity).
Non-myeloablative (also called low intensity or mini transplant).

Your care team will tell you which type is best for you.

Why do a transplant?

With allogeneic transplants, providers look for the "graft versus tumor effect". This is the effect that the donor's immune system (which is part of the marrow that the donor donated) has on the recipient patient's cancer cells. The hope is that the healthy donor immune system can attack any stray cancer cells in the patient that survived the preparative regimen.

How is the transplant done?

After the preparative regimen, you will rest for 1 or 2 days. This will help clear the chemotherapy so it will not damage the donor cells. The day of the transplant is sometimes called “Day 0”.

On the day of the transplant, you are given some medications (called pre-medications) to prevent any reactions to the DMSO preservative.
You will also get intravenous (IV) fluids.
Your blood pressure and heart rate are closely watched. Once you have received the pre-medications, the frozen stem cells are thawed. They are given back to you like a blood transfusion. They are given through your intravenous line.

The stem cells go to the bone marrow space and start making new cells to replace all those that were killed ("ablated") by the chemo. Even though they are making cells, your body’s immune system is not working how it should be.

What happens after the transplant?

Right after the transplant, while you are waiting for cells to be made, is called the "nadir". It is often the hardest part. The blood cell counts are very low, putting you at risk for infections, bleeding, and severe fatigue. You do not have any white blood cells to fight infections, so you may have fevers and need antibiotics. All visitors and healthcare staff must wash their hands before entering your room. Anyone who is sick or lives with someone who is sick should stay home.

Low platelet counts can lead to bleeding, and platelet transfusions are common during this time. A low red blood cell count (called anemia) can also be hard. You may look pale, feel very tired, and need red blood cell transfusions. Many patients say the worst side effect is extreme fatigue. Just getting out of bed is a chore. When able, short walks in the halls or light exercise in your room can increase your energy.

You must also deal with the side effects of the chemotherapy you had. These can be diarrhea, nausea and/or vomiting, hair loss, fever, chills, decreased appetite, and mouth sores (called mucositis). Every patient is different, and it is hard to tell who will have more side effects. The chemotherapy medications used before the transplant can vary, and some medications are more likely to cause certain side effects than others.

You will be in the hospital during this time where your health can be closely monitored. During this time, you may want and need the support of your family. You may also not be feeling well and just want to rest. Be honest with your loved ones about how they can be helpful. You may also want to have one person that you update each day be the contact person for other loved ones. Your visitors may need to take special precautions when visiting you so that you do not get sick. Ask the oncology team what protocol they will need to follow.

What is engraftment?

Engraftment is the point when the stem cells start doing their job and blood cell counts start to come up. It can take about 7 to 12 days after Day 0 for the stem cells to make new cells, and for those new cells to work the way they should.

The first number your care team will look for is the neutrophil count, which is the type of white blood cell that is most important in fighting infection. The care team will watch your neutrophil count and when it reaches a certain level, you can stop antibiotics and, in some cases, go home.
The red blood cell and platelet counts can take a few weeks to get back to a normal range and you may need transfusions.

You will start to feel better as your numbers come up. Your providers will tell you what you need to do to stay as healthy as possible when you go home.

What are the potential complications of this transplant?

Some side effects of allogeneic transplants are:

Graft Versus Host Disease (GVHD) is when bone marrow or stem cells that come from a donor start to attack the cells of the person who received the transplant. You will be given medication to prevent and treat it. A good part of GVHD is the graft versus tumor effect which allows the donor cells to attack any cancer cells. GVHD will be managed but not completely get rid of it, so that you can benefit from the graft versus tumor effect.
Graft rejection can happen if there are immune system cells left in the patient after the preparative regimen. These "native" cells then attack the donor's cells because they recognize them as foreign to the body. This can be prevented most of the time by making sure the preparative regimen is strong enough to kill any native immune cells.
Graft failure can happen when the donor's cells fail to start working (producing new blood cells). Healthcare providers usually consider a diagnosis of graft failure if engraftment has not happened by about 42 days after transplant. This is rare and the only treatment is to get another transplant.
Lung and liver issues can be very serious. Your care team will watch you closely for these signs:
- Pneumonia.
- Veno-occlusive disease (VOD) of the liver which can cause jaundice (yellowing of the skin and eyes).
- Enlarged liver.
- Swelling of the abdomen (belly).

You will be watched closely for any side effects so that they can be managed. Tell your providers if you are having any new or worsening side effects.

What is a mini-allo or reduced-intensity transplant?

This type of allogeneic transplant uses a less intense preparative regimen before the donor cells are given. Often, radiation and anticancer medications are used but not chemotherapy. Unlike a traditional transplant, cells from both the donor and you may exist in your body for some time after a mini-allo.

What happens when I am discharged?

Transplant centers vary in how they handle the time for discharge. Once you go home, you will need to visit the clinic often, maybe even daily. Most centers require you to stay near the hospital for the first 100 days after transplant. Even though the blood cells have started to work, it will be months to a year before you will have a "normal" immune system. You need to be very careful to avoid infection (avoiding crowds, washing hands frequently, wearing a mask in public places). Your energy level will not be like your "old self" for quite some time (some say years). Friends and family must understand that just because the transplant is over, it does not mean you are back to normal.

Transplant centers give detailed instructions to families who will be having the transplant patient stay at their home. These include help with chores, childcare, pet care, and other daily household errands. The National Marrow Donor Program has some great resources for preparing the home for a transplant recipient. This can be a lot of work, but it is a great way for friends and family to help out.

An allogeneic transplant is not the right treatment for everyone. Your care team will tell you if an allogeneic transplant is right for you and what kind you will have. Talk to your provider about any questions you have.