Stem cell transplantation (i.e., bone marrow, stem cells, or cord blood) is used to treat several types of childhood cancers. In these procedures, the child or teen is given high doses of chemotherapy and/or radiation to destroy all of the cancer in the body. During this process, the bone marrow is totally destroyed. Normal marrow or stem cells are then infused into the child’s veins. The marrow or stem cells migrate to the cavities inside the bones where new, healthy blood cells are then produced.

The three types of transplants are:

• Allogeneic.  Allogeneic transplants are those in which donor bone marrow, stem cells, or cord blood is transplanted into the patient. The cells usually come from a sibling with a matching marrow type or a matched unrelated donor. In some cases, parents are used as donors. The risk of complications increases if the donor is mismatched or unrelated.

• Syngeneic.  Syngeneic bone marrow transplants (BMTS) are those in which the donor is the patient’s identical twin. Many late complications are avoided because the marrow is an identical match.

• Autologous.  During an autologous stem cell transplant, the patient’s own stem cells are extracted and cryopreserved (a type of freezing). The patient then undergoes radiation and chemotherapy, or high-dose chemotherapy alone. The frozen cells are thawed and infused into the child or teen intravenously.

The three sources of blood cell used for transplant are:

• Bone marrow.  In a BMT, the donor’s bone marrow is extracted from the hip bones. This is done in the operating room with the use of two large bore needles.

• Peripheral blood stem cells.  For a peripheral blood stem cell transplant, the patient’s or donor’s stem cells—cells from which all other cells evolve—are harvested in a procedure called apheresis. Blood is removed through a catheter or vein in the arm and circulated through a machine that extracts the stem cells. The remaining blood is then returned to the patient or donor.

• Umbilical cord blood.  Umbilical cord blood is a rich source of stem cells. In the 1990s, researchers began conducting transplants using the umbilical cord blood obtained during the birth of a sibling or from preserved unrelated donor cord blood.

Prior to the transplant, the patient’s bone marrow is destroyed using high-dose chemotherapy with or without radiation. This portion of treatment is called conditioning. The purpose of the high doses of chemotherapy and radiation is to kill all remaining cancer cells in the body, make room in the bones for the new bone marrow, and suppress the patient’s immune system so it will accept the donor’s marrow.

Conditioning regimens vary according to institution and protocol, and also depend on the medical condition and history of the child or teen. Typically, chemotherapy is given for 2 to 6 days, and radiation (if part of conditioning) is given in multiple small doses over several days. The drugs most commonly used during conditioning are cyclophosphamide (Cytoxan ^® ), busulfan (Myleran ^® ), etoposide (VP-16 or Vepesid ^® ), thiotepa, and melphalan (Alkeran ^® ).

The transplant itself consists of simply infusing the stem cells or marrow through a catheter or intravenously into the patient, just like a blood transfusion. The stem cells travel throughout the blood vessels, eventually filling the empty spaces in the long bones. Engraftment occurs when the new marrow begins to produce healthy white cells, red cells, and platelets—usually 1 to 4 weeks after transplantation.

Late effects

This section briefly outlines some common and uncommon late effects from treatment with stem cell transplantation. Remember that you may develop none, one, or several of these problems in the months or years after treatment ends.

Graft-versus-host disease. Graft-versus-host disease (GVHD) is a frequent complication of allogeneic stem cell transplants. It does not occur with autologous or syngeneic transplants. In GVHD, the bone marrow provided by the donor (the graft) attacks the tissues and organs of the BMT child (the host). Approximately 30 to 50 percent of children and teens who have a related HLA-matched transplant develop some degree of GVHD. The incidence and severity of GVHD are increased for those children and teens who receive unrelated or mismatched marrow.

There are two types of GVHD: acute and chronic. Children and teens can develop one type, both types, or neither one. Acute GVHD usually occurs at the time of engraftment or shortly thereafter. Donor cells identify the patient’s cells as different and attack the patient’s skin, liver, stomach, or intestines. Acute GVHD is treated with cyclosporine, tacrolimus (Prograf ^® ), and steroids (i.e., prednisone, dexamethasone). Prolonged use of steroids to treat GVHD can cause osteonecrosis (death of the small blood vessels that feed bones). For detailed information about these late effects, see Chapter 15 and Chapter 18 .

If chronic GVHD develops, it usually starts 100 or more days post-transplant. It primarily affects the skin (itchy rash, discoloration of the skin, tightening of the skin, hair loss with a dry flaky scalp, nail changes—dry and brittle), eyes (dry, light sensitive), mouth and esophagus (dry mouth, tooth decay, difficulty swallowing), intestines (diarrhea, cramping, weight loss), liver (jaundice), lungs (shortness of breath, wheezing, coughing), and joints (decreased mobility). Survivors with chronic GVHD can develop one, a few, or several of these problems. There are many medications, including tacrolimus (Prograf ^® ), steroids, and mycophenolate (CellCept ^® ), that can be used to treat chronic GVHD.

Cataracts. Numerous late effects can occur from total body irradiation (TBI) used during conditioning. Often, children and teens develop cataracts after transplant. If the TBI is given in one dose, the likelihood of developing cataracts is much higher than if TBI is given in smaller doses over several days (called fractionated). Currently, if radiation is used, it is given in fractionated doses. Decreased tear production is also common after transplant. For more information, see Chapter 10 .

Growth problems. Radiation can affect growth. Children who received prior cranial radiation, spinal radiation, or total body radiation should be monitored for learning disabilities, dental problems (e.g., facial bone and jaw growth, delayed development of permanent teeth, incomplete root development), and growth hormone deficiency resulting in delayed or decreased growth. Children and teens who receive TBI also may have a low thyroid function due to decreased production of thyroid hormone. For more information, see Chapter 9 .

Problems with puberty. For the most part, children and teens who were given only cyclophosphamide during conditioning have normal sexual development. Children and teens who had TBI, however, may experience delayed puberty (the incidence is lower if the radiation was given in several small doses). All children and teens who received TBI should be followed closely by a pediatric endocrinologist who can prescribe hormones to assist in normal pubertal development. Girls are more likely than boys to need hormonal replacement; boys usually produce testosterone but not sperm.

Fertility. Children and teens who received TBI usually—but not always—become sterile; that is, after growing up, girls will not be able to become pregnant, and boys will not be able to father children. The ability to have a normal sex life is not affected. Some children treated with cyclophosphamide but no radiation have remained fertile, and to date, all offspring have been normal. For more information, see Chapter 9 .

Hepatitis C. Infection with the hepatitis C virus can develop in survivors who had blood transfusions prior to July 1992. For more information, see Chapter 15 .

Second cancers. Children or teens who received a stem cell transplant have a small risk of developing a second cancer, particularly if TBI was used. The type of cancers most commonly seen post-transplant are leukemia, lymphoma, and bone and soft tissue sarcomas. For more information, see Chapter 19 .

TBI can also cause late effects to the lungs, heart, liver, and bowel. Any body system treated with radiation can be damaged, so follow-up needs to be done for the rest of one’s life.