The Bone Marrow Transplant Process: What to Expect

Before the stem cells can be given to a patient, they are first collected or "harvested" from a donor.

The harvest site of the stem cells is different depending on the type of stem cells that will be used for the patient. Stem cells come from either the bone marrow, peripheral blood (from a vein) or blood from the umbilical cord.

Types of stem cell transplants include:

• Autologous: a transplant where the patient gets their own blood stem cells back. Sometimes this may also be called a "stem cell rescue."
• Matched related/matched sibling: a transplant where the patient (also called the recipient) gets blood stem cells from their sibling or family member because they have the same HLA type (these are immune markers that you inherit from your parents).
• Match unrelated: a transplant from a non-family member who has the same HLA type
• Umbilical cord blood: a transplant where the blood stem cells were collected from an umbilical cord shortly after the birth of an infant. These can be related (from a sibling) but are most commonly from a non-family member. These cells have been frozen in a deep freeze until they are ready for use.
• Haploidentical: a transplant from a person that shares only half of your HLA type, such as your mother or father. Sometimes, a sibling can also be a haploidentical donor, depending on how you each have inherited your HLA types from your parents.
• Unmatch unrelated: These cells are usually partially HLA matched, or may be modified cells that do not react to HLA type mismatches. These may also be called "off the shelf" cells, since it requires little or no HLA matching. These cells are not used currently for a traditional blood or marrow transplant, but rather are used to give a patient engineered cells for a specific reason, such as for bad viral infections.

What's the difference between autologous and allogeneic bone marrow transplants?

There are two primary types of stem cell collection. Autologous stem cells are stem cells from the patient that are collected using. Allogeneic stem cells are stem cells from another person using peripheral blood collection, bone marrow collection or cord blood collection.

Peripheral blood collection (autologous)

Peripheral blood collection happens after the patient has received a special medicine called G-CSF. for several days. This medicine helps move the stem cells from the bone marrow into the donor's blood steam and helps increase the number of white blood cells and stem cells in the blood.

A provider will place large IVs, PICC lines or a central line into the patient's arms. Then they will hook up the patient to an apheresis machine that collects the stem cells and returns the other blood cells back into the body. This happens in the specialized stem cell apheresis center within the Blood Donor Center, as an outpatient visit and takes about 5 to 8 hours over the course of 1 to 5 days. The length of time depends on how many stem cells are needed and how easy it is to get that amount. After all the cells are collected each day, they are frozen and can be given later. The donor is awake and able to talk during the whole collection.

Bone marrow collection (allogeneic)

If the stem cells come from bone marrow, a provider will place a special needle into the donor's hip to remove stem cells. The procedure occurs in an operating room and the donor is asleep (under anesthesia) during the procedure so they will not feel the needle.

The donor's body will quickly remake bone marrow to replace what has been donated. After the marrow is harvested, it is filtered to remove fat, clots and bone pieces. It's then sent to the lab to be processed. Sometimes it is frozen, but most of the time it is given to the patient the same day.

Cord blood collection (allogeneic)

Providers collect unused cord blood stem cells from the umbilical cord and placenta very shortly after a baby is born. This sterile process happens after the cord is clamped and cut. Cord blood collection does not hurt the baby in any way.

The cells are then frozen to be used later for transplant. If cord blood was saved from the family members of the patient, it can be used if it is a match. However, most of the time, the cord donors are from people the patient does not know.

Consultation before transplant (pre-BMT)

Your child will meet with your primary transplant doctor to discuss the disease and how appropriate a blood or marrow transplant is for treating it. You will discuss potential risks and benefits of transplant versus no transplant, your transplant preparative regimen (the high-dose chemotherapy or total body irradiation given prior to your transplant) and possible donors for your transplant.

If you and your BMT physician decide to proceed to transplant, you will have a thin, flexible IV tube, called a central venous catheter (also called a central line or Broviac) surgically inserted into a large vein in your chest near the heart. The central line is placed for the administration of your preparative regimen chemotherapies, the stem cell infusion and any fluids and medications you may need during and after your transplant.

Preparative regimen

Several days prior to your transplant, you will receive high-dose chemotherapy and/or total body irradiation. This is called the preparative or conditioning regimen. The preparative regimen is designed to kill your diseased cells and/or make room in your bone marrow for healthy blood stem cells.

The preparative regimen will take place in the hospital or in an outpatient clinic over several days. The chemotherapy drugs are given through your central venous catheter. During this time, you may have side effects from the preparative regimen including nausea, vomiting, diarrhea and/or mucositis (inflammation of your mucous membranes, such as your mouth and GI tract). Your BMT team will review the common side effects of your preparative regimen with you before your preparative regimen begins, since each regimen has its own possible side effects.

To counteract the side effects, your BMT team will give you anti-nausea and pain medicines. If vomiting and/or diarrhea are severe, they may give you supplemental nutrition via a nasogastric tube (a small spaghetti-sized tube that goes to your stomach to provide liquid nutrition), IV fluids or total parenteral nutrition (TPN, which provides IV fluid and nutrition). After starting the preparative regimen, white blood cells slowly die off, but may not be completely gone by the day of transplantation.

Stem cell infusion ("day 0")

Stem cells from a donor (allogeneic) or from the patient themselves (autologous) will be infused into the patient using their central venous catheter in their hospital room. The bag of cells to be infused often looks like a regular blood or platelet transfusion. Before the infusion, patients are given acetaminophen (Tylenol), diphenhydramine (Benadryl) and hydrocortisone to prevent any immediate reactions to the infusion.

If the cells are from donated marrow, they will be filtered in the laboratory and concentrated before being infused into the patient. If the cells were previously frozen, such as an autologous cell collection or cells from an umbilical cord, the cells will be thawed shortly before they are infused. These cells are frozen using a special preservative called dimethyl sulfoxide (DMSO) that prevents the cells from breaking during the freezing process. DMSO creates a distinct smell during and after infusion and may cause some short-term side effects such as high blood pressure.

Immunosuppressive therapy

If the patient is receiving cells from another person (allogeneic) or an umbilical cord, they will require immunosuppressive medications to prevent rejection of the new stem cells and to prevent the new cells from attacking the patient, called graft-versus-host disease (GVHD). Usually, the immunosuppressive medicines are started shortly before the transplant and are continued for several months after transplantation.

During the time the patient is on immunosuppressive medicines, they will need to be very conscious of staying away from sick people. They are also at increased risk of developing viral infections, such as EBV, CMV, Adenovirus and HHV6, so weekly blood draws are necessary – even if the patient does not have symptoms. If, after several months, the patient does not have any signs of GVHD, we will slowly taper the immunosuppressive medications, giving the body time to adapt.

When the infusion is done, the waiting begins for the stem cells to find their new home in your child's bone marrow. During this time, which usually takes several weeks, the new bone marrow starts making its own red cells, white cells and platelets.

This is also the same time that nadir happens (when the chemo side effects are the worst and blood counts are low). Because of nadir, your child is at a high risk of infection and may need blood transfusions. To decrease the infection risk, we will give your child antibiotics by mouth and through the central line. It is important that your child has good personal hygiene, exercise or activity and eats a well-balanced diet to decrease infection risks and help their body recover.

The process of stem cell growth is called engraftment. Your medical team will monitor how several types of blood cells engraft, including neutrophils (a type of white blood cell that fights bacteria and fungus), red blood cells (blood cells that transport oxygen to the tissues) and platelets (cells that form clots and prevent bleeding).

Side effects of BMT

The preparative chemotherapy and other medications your child receives during the transplantation process may cause your child to have several side effects. Most commonly, children develop nausea and vomiting during the chemotherapy, though these side effects can often linger for several days to weeks after the chemotherapy is complete. Additionally, some preparative regimens can lead to a patient developing mucositis, hair loss, skin darkening or rash. These and other possible side effects of transplant will be discussed at your pre-transplant consult.

Infections: Even though we have special rules on the BMT unit and we give our transplant patients preventative antibiotics, infections still happen. We will monitor your child for a fever and other signs of infection. If your child has a fever, we will draw blood cultures and may prescribe or change antibiotics. With some infections, we may get X-rays, CT scans or other special tests to figure out the cause. Also, because of the known increased risk of viral infections, we routinely monitor for viruses in the blood, even if the patient doesn’t have symptoms.

Transfusions: Platelet and red blood cell transfusions will be needed after a BMT. We will check blood cell levels daily and give transfusions based on blood levels or symptoms.

Nutrition: Good nutrition is very important to recover from BMT. Due to nausea and changes in taste associated with the preparative regimen and other medications, most patients have a poor appetite during transplantation.

We will check your child's calories daily by counting everything they eat. If they are not eating enough, we can give them extra calories and nutrients through a tube in their nose (called a nasogastric tube or NG tube) or through their central line, called total parenteral nutrition (TPN). If your child is still not getting enough calories by the time they're ready to go home, they may have to get NG feeds or TPN at home. This will continue until they are able to eat enough on their own.

Discharge: Your child will stay in the hospital until there is a significant neutrophil engraftment. It may take 10 to 28 days before there are signs that the neutrophils are growing and producing new blood cells. After neutrophil engraftment, other issues may need to be resolved before they leave the hospital. This includes any fever or infections, graft-versus-host disease, the need for daily transfusions, daily medication intake difficulties and more. The need for frequent medical care can also lead to a longer stay, which will be discussed at your pre-transplant consult.

What precautions do we need to take after transplant?

Though neutrophils start growing within a few weeks after the BMT, other immune cells (such as T cells) take several months to grow and work correctly. Because of this, we ask our patients to wear a special mask that helps prevent respiratory infections and to avoid sick people and crowded public places until we can confirm the rest of their immune system is working properly.

Late effects of bone marrow transplant

While the main goal of BMT is to cure the illness, there are many things to think about afterward. These are known as late effects and can include the emotional, medical and physical well-being of the patient and family. Regardless of what your child may need, we are here to help.

Late effects of BMT can be caused by chemo, radiation, the transplant, original illness or any combination of these. This can include problems with:

• Hormones and thyroid function
• Eyes
• Heart function
• Tooth decay
• Osteoporosis and joint problems
• Learning and memory issues
• Sun sensitivity and predisposition to skin cancer
• Possibility of secondary cancer (developing another cancer later in life)