Allogeneic Bone Marrow Transplant

What is an allogeneic bone marrow transplant?

An allogeneic bone marrow transplant replaces damaged or destroyed blood and bone marrow cells with healthy ones from a donor. In this kind of transplant, healthy cells are taken from someone other than your child. (Learn about a transplant that uses your child’s own bone marrow cells: autologous bone marrow transplant.)

Blood-making cells live in the spongy area of bones known as marrow. These cells develop into all types of blood cells in the body. In an allogeneic bone marrow transplant, the donated healthy cells grow and produce normal blood cells that help fight disease.

This process may also be used when your child’s diseased marrow has been destroyed using chemotherapy or radiation therapy.

What are allogeneic bone marrow transplants used to treat?

These transplants are used to treat disorders such as:

• High-risk leukemias or lymphomas
• Some high-risk solid tumors
• Immune system diseases
• Sickle cell disease
• Thalassemia
• Bone marrow failure syndromes
• Metabolic storage disorders

What happens before an allogeneic bone marrow transplant?

First, a person must be found to donate healthy bone marrow for the patient. The donor can be a relative or unrelated. 

• A related donor is often a brother or sister with the same tissue type as your child. A parent’s cells may be used if there is no closely matched sibling. St. Jude pioneered a process known as a haploidentical transplant. This process uses a donor—usually a parent—who is only a partial genetic match. Haploidentical donors are now used around the world. 
• If no relatives are available, the cells may come from a volunteer donor who is well matched. Unrelated donors are found through the National Marrow Donor Program.
• Your child's donor will undergo tissue typing, also called human leukocyte antigen (HLA) matching:
  • HLAs are markers the body uses to decide if a “foreign” substance belongs in the body or should be destroyed. Donor "matching" involves looking at the HLA of the donor and patient. Big differences in donor and patient HLA can lead to donor and patient cells attacking or destroying each other. For example, if a patient's cells attack new donor cells, the donor's blood and marrow cells are rejected. The opposite can also occur. If a donor's cells attack existing patient cells, that process is called graft-versus-host disease (GVHD).

Donor cells can be collected in several ways:

• If donor blood marrow is used, doctors usually insert a needle into a bone (often the pelvis) of the donor to pull out the marrow. In general, this outpatient process lasts about an hour. A donor may need oral (by mouth) pain medicines for three to four days afterward.
• Another method uses blood cells that circulate throughout the body. The donor takes drugs that increase the number of these cells in the blood stream. Those blood cells can then be collected from a vein in a method similar to a blood donation.
• Donor blood-making cells can also be collected after birth from the blood left in the placenta or the baby's umbilical cord.

Before transplant, your child may receive chemotherapy, radiation therapy and/or antibodies. This is called the preparative or conditioning regimen. This therapy aims to: 

• make space in the bone marrow for new donor cells
• kill any cancer cells that may be left in the body
• weaken existing normal immune system or blood cells, so that the body is more accepting of the new donor cells.

The conditioning regimen increases the chance that the transplant will be successful. The therapy may include the following:

• Chemotherapy (“chemo”)—uses powerful medicines to kill cancer and normal cells, or stop them from growing (dividing) and making more cancer cells.    
  • Chemo may be injected into the bloodstream, so that it can travel throughout the body.
  • Some chemo may be given by mouth.
  • Combination therapy uses more than one type of chemo at a time.
• Radiation therapy—uses high-energy X-rays or other types of radiation to kill cancer and normal cells and stop them from growing.
  
• Antibodies are proteins that specifically recognize parts on the surface of cells. These are used to destroy the patient's immune system an dreduce the risk of GvHD.

How are allogeneic bone marrow transplants done?

After the chemotherapy and/or radiation treatment, the donor’s healthy stem cells are transplanted into your child’s bloodstream:

• The procedure is similar to a blood transfusion. The cells are given slowly through a vein.
• The cells travel through the blood until they reach the marrow and start growing new, healthy cells. The time required for the new donor cells to start to grow varies between different transplant types and can take from 2—4 weeks.

What problems can occur with allogeneic bone marrow transplants?

Before the treated bone marrow can begin producing new, healthy cells, the following issues could occur:

• Side effects from the conditioning regimen
• Rejection or graft failure if the new donor cells are destroyed or do not grow well
• Infection because fewer white blood cells (or immune cells) are present to protect the patient
• Anemia caused by fewer red blood cells 
• Blood-clotting and bleeding problems caused by low platelet levels 

After the new donor cells have grown:

• GvHD may occur if the donor cells see the patient's normal cells as different and attack them.
• Infections remain a risk for several months as the new donor cells grow and mature.
• Patients may have problems from the therapy they received earlier to treat their underlying disease or as part of the transplant.
• Patients may undergo disease relapse or reoccurrence.

What are the survival rates for allogeneic bone marrow transplants?

Five-year survival rates for patients treated with allogeneic bone marrow transplants vary widely, depending on:

• The disease being treated
• How far it has advanced
• Other health problems the child may have

Overall survival has greatly increased in the last few years for patients who received their first allogeneic transplant at St. Jude. One-year survival has been over 70% in these high-risk patients. 

Why come to St. Jude for an allogeneic bone marrow transplant?

• St. Jude is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children.
• St. Jude has created more clinical trials for cancer than any other children’s hospital in the United States.
• The nurse-to-patient ratio at St. Jude is unmatched— averaging 1:3 in hematology and oncology, and 1:1 in the Intensive Care Unit.
• St. Jude has one of the world’s largest hematopoietic stem cell transplant programs dedicated to caring for children, teens and young adults. Since the first hematopoietic stem cell transplant at St. Jude was performed in 1982, the Transplant Program has performed more than 3,200 transplants.
• St. Jude is accredited by the Foundation for the Accreditation of Cellular Therapy (FACT) for autologous and allogeneic peripheral blood and marrow transplantation in children and adults.
• The Transplant Program at St. Jude has been a part of the National Marrow Donor Program (NMDP) since 1990. Our center also provides data to the Center for International Blood and Marrow Transplant Research.
• St. Jude was the first institution to perform an allogeneic bone marrow transplant in a patient with sickle cell anemia.
• To improve outcomes and reduce side effects associated with transplants, doctors in the St. Jude Transplant Program work closely with laboratory scientists to rapidly move discoveries from the lab to the clinic.
• St. Jude support staff members have been specially trained to care for children receiving transplants.
• St. Jude transplant physicians have been pioneers in the use of T cell depletion to provide safe and effective allogeneic transplants using haploidentical donors. More than 500 patients have received cells from these kinds of partial donors at St. Jude. During that time, the rate of three-year overall survival has more than doubled, and is now over 75% for patients with high-risk leukemia who come to transplant in remission. 
• Early discoveries showwed that certain cancer-fighting immune cells from the donor, called natural killer (NK) cells, can be helpful when a protein called KIR is present. 
• Research from the St. Jude transplant team has shown that haploidentical donor memory T cells can give positive effects without increasing the risk of GvHD.
• St. Jude scientists made major discoveries that heavily influenced the development of chimeric antigen receptor (CAR) modified T-cell therapies. This led to the first FDA approved T-cell therapy for acute lymphoblastic leukemia.
• St. Jude scientists continue to research CAR T-cell therapies, with the goal of having safe and effective therapies for leukemia, solid tumors and brain tumors.