Stem Cell Transplant and Cellular Therapies Program

Every type of blood cell in the bone marrow begins as a stem cell. Stem cells are immature cells that are able to produce other blood cells that mature and function as needed. Stem cells are the most important cells needed in a blood and bone marrow transplant. Stem cells, when transplanted, find their way to the recipient’s marrow and begin to differentiate and produce all types of blood cells that are needed by the body. Healthy stem cells come from three different sources:

Bone marrow is sponge-like tissue that fills the hollow space inside bones. The bone marrow is responsible for the development and storage of most of the body’s blood cells. This tissue contains the stem cells that produce red blood cells, white blood cells, and platelets. When a portion of a person’s bone marrow is collected for transplantation, it is called a “bone marrow harvest.”

Peripheral blood is blood that circulates in the blood stream. Peripheral blood contains the same blood producing cells that are present in bone marrow. When a person’s peripheral stem cells are collected for transplantation, it is called a “peripheral blood stem cell collection” or “apheresis”.

Umbilical cord blood is found in the umbilical cord of a newborn baby and is a rich source of stem cells that can be used in transplantation. Cord blood is collected from the umbilical cord of a newborn baby immediately after delivery. Once the cord blood has been collected, it is frozen and stored at a cord blood bank for future use. The stored cord blood is called a “cord blood unit (CBU).” Cord blood collection is a non-invasive procedure that is not harmful to either the mother or baby.

Failure of the graft (transplant) taking hold in the marrow is a potential complication. Graft failure may occur as a result of infection, recurrent disease or if the stem cell count of the donated marrow was insufficient to cause engraftment. Graft failure may be treated with an additional marrow transplant if a source is available.

Graft-versus-host disease (GVHD) can be a serious and life-threatening complication of a bone marrow transplant. GVHD occurs when the donor’s immune system reacts against the recipient’s tissue. The new cells do not recognize the tissues and organs of the recipient’s body. The most common sites for GVHD are the gastrointestinal tract, liver, skin, and lungs. GVHD is graded from I to IV and can be acute (occurs suddenly or during the early period of transplant) or chronic (occurs over a period of time or during the later period of transplant). The child will be monitored closely for signs and symptoms of GVHD. Diarrhea, fever, rash, skin changes, abdominal pain, respiratory complications and decreased liver function may be present with GVHD. Medications are given prior to transplant to reduce the risk of this complication.

Donors and cord blood units are carefully screened and tested. These tests are done to reduce the risk that a donor could pass a disease to a transplant patient. Before they are approved to donate, donors:are tested for infectious diseases such as AIDS and hepatitis.
answer questions about their health history. This helps doctors find risks if the donors have an infectious or hereditary disease.
iare checked by doctors for signs of disease.

Marrow and cord blood donations are thoroughly screened, much the same as regular blood donations. Even so, donated whole blood cannot be guaranteed 100% free of infectious diseases. In the same way, the risk that donated blood or marrow cells carry a disease cannot be completely eliminated.

The preparations for a transplant vary depending on the type of transplant, the disease requiring transplant and the child’s tolerance for certain medications. Most often, high doses of chemotherapy and/or radiation are included in the preparations. This intense therapy is required to effectively treat the malignancy and make room in the bone marrow for the new cells to grow. After the chemotherapy and/or radiation is administered, the transplant, either from bone marrow, cord or from peripherally collected stem cells, is given through the central venous catheter into the bloodstream. It is not a surgical procedure to place the marrow into the bone, but is similar to receiving a blood transfusion. The stem cells find their way into the bone marrow and begin reproducing and establishing new, healthy blood cells.

Supportive care is given to prevent and treat infections, side effects of treatments, and complications. This includes frequent blood tests, close monitoring of vital signs, strict measurement of input and output, weighing the child daily (or twice daily), and providing a protected and sterile environment. The days before transplant are counted as minus days. The day of transplant is considered day 0. Engraftment and recovery following the transplant are counted as plus days. For example, a child may enter the hospital on day -8 for preparative regimen. Days +1, +2, etc., will follow. There are specific events, complications, and risks associated with each day before, during, and after transplant. The days are numbered to help the child and family understand where they are in terms of risks and discharge planning. Depending on the type of transplant and the disease being treated, engraftment usually occurs around day +15 or +30.

During infusion of bone marrow, the child may experience some or all of the following symptoms:

nausea / vomiting
chills
fever
hives
chest pain
discomfort

After infusion, the child may:

spend several weeks in the hospital.
be very susceptible to infection.
experience excessive bleeding.
have blood transfusions.
be confined to an environment that will prevent them from being infected from sick people. take multiple antibiotics and other medications.
be given medication to prevent graft-versus-host disease (if the transplant was allogeneic). The transplanted new cells (the graft) tend to attack the child’s tissues (the host), even if the donor is a relative, such as a brother, sister, or parent.
undergo continual laboratory testing.
experience nausea, vomiting, diarrhea, mouth sores and extreme weakness.
experience temporary emotional or psychological distress.

Matching involves typing human leukocyte antigen (HLA) tissue. The antigens on the surface of these special white blood cells determine the genetic make-up of a person’s immune system. There are at least 100 HLA antigens; however, it is believed that there are a few major antigens that determine whether a donor and recipient match. The others are considered “minor” and their effect on a successful transplant is not as well defined.

Immediate family members can take a blood test called “HLA Typing” to determine if there is an HLA matched donor in the family. This test is different than ABO blood typing. If no family donor match is found, the physician may request to search for an unrelated donor. Unrelated donor searches are performed through The National Marrow Donor Program (NMDP). The NMDP has developed a registry of volunteer blood and marrow donors thar may be accessed to search for a donor on behalf of a patient in need of a BMT. Searching for an unrelated donor can take several months, sometimes even years. CHOC Hospital is a transplant center and as such, we only test immediate family members (siblings and parents) to see if they are a match. There are two ways to test if extended family members and friends are a match to the patient. Family and friends can join the Be The Match registry by being available to be a potential donor not only for the child but also for any other patient somewhere in the world needing a transplant. To qualify to join to join the registry, donors must be between 18 and 60 years of age and must pass a health screening questionnaire. A southern California Be The Match center is located a few miles from CHOC Children’s in Santa Ana and can be reached through the organization’s national hotline at (800) 526-7809. Donations are accepted in order to offset the cost of adding new members to the registry. Private testing that does not put family members on the worldwide donor registry can be done for a fee that is not covered by insurance. This is also an option for friends and family who do not meet the Be The Match age requirements. The results of the test will only be available to the potential donor. For additional information or to order a kit, call (877) 565-3287.

Extended family members and friends can donate umbilical cord for specific patient use; however, this is considered private banking, is subject to a storage fee and must be collected at St. Joseph Hospital next to CHOC. It is recommended that umbilical cords from infants born at St. Joseph Hospital be donated for public use through the national registry. For more information, please contact the CHOC Cord Blood Bank at (714) 509-4335.

For the child receiving the transplant, the following will occur in advance of the procedure:

Prior to the transplant, an extensive evaluation is completed by the Blood and Marrow Transplant (BMT) team. All other treatment options are discussed and evaluated for risk-versus-benefit.

A complete medical history and physical examination are performed, including multiple tests to evaluate the child’s blood and organ functions (i.e., heart, kidney, liver, lungs).

A child will often come to the CHOC BMT center seven to 14 days prior to transplant for hydration, evaluation, placement of a catheter (also called a “central venous line”) and other preparations. The central venous line is surgically placed in a vein in the chest area. Blood products and medications will be administered through the catheter.

A suitable (tissue-typed and matched) donor must be available.

One should expect a prolonged hospitalization for BMT admission, which could be at least four weeks or a few months. Hospital discharge following a transplant depends on many factors, including the following:
extent of engraftment,
presence of complications,
the patient’s overall health, and
suitable living arrangement must be available within a 50 mile radius from the hospital.

Frequent visits to the child’s transplant team will be required after discharge to determine effectiveness of treatment, detect complications, detect recurrent disease and to manage the late effects associated with a transplant. The frequency and duration of visits will be determined by the patient’s transplant team. Initially, clinic visits are one to two times per week and as the child recovers, it spreads out to weekly or every other week and so on.

Donor sources available include: self, sibling, parent or relative, non-related person, or umbilical cord blood from a related or non-related person. There are national and international registries for non-related people and cord blood. For family members, they may choose to have their blood typed to check for bone marrow compatibility because of the desire to help. This testing is called HLA (Human Leukocyte Antigen) typing. These relatives may choose to have their HLA typing results registered for use for other recipients in need of a donor. If the potential donor is notified that they may be a match for a child needing a transplant, they will undergo additional tests. Tests related to their health, exposure to viruses and a complete genetic analysis will be done to determine the extent of the match. The donor will be given instructions on how the donation will be made. Once a donor for a child needing a transplant is found, then stem cells will be collected either by a bone marrow harvest (collection of stem cells with a needle placed into the soft center of the bone marrow) or peripheral blood stem cell collection or “apheresis” (stem cells that are collected from the circulating cells in the blood). A bone marrow harvest is performed under general anesthesia by two physicians. The procedure generally takes approximately an hour and the donor is usually released the same day, after a few hours, after recovery. A slight discomfort to the pelvic bone areas and fatigue is usually experienced after the procedure, but subsides within a few days and donors can return to normal activities at this time. A peripheral blood stem cell collection or “apheresis” procedure takes approximately four to six hours. A peripheral IV or central line is placed into a large vein and the stem cells are collected. The donor should be released the same day after the procedure. A slight discomfort to the line insertion areas and fatigue is usually experienced after the procedure. The donor can return to work when their fatigue subsides a few days after the donation.