Cord Blood Transplants

During pregnancy, the umbilical cord provides a lifeline between mother and child. Now, it may also give new life to the child years after birth, or be a lifesaver for another child.

Like bone marrow, the umbilical cord is rich in stem cells—the primitive cells from which all types of blood cells evolve. When patients with bone marrow disorders such as aplastic anemia or leukemia, or certain solid tumor cancers, are treated with high dose chemotherapy and/or radiation, the stem cells in their bone marrow are destroyed. Unless those stem cells are replaced, the patient’s body cannot produce sufficient white blood cells to fight infection, red blood cells to carry oxygen to organs and tissues, and platelets to control bleeding.

Traditionally, bone marrow has been transplanted into patients following high dose chemotherapy and/or radiation to provide a new source of stem cells. In some cases, “peripheral blood stem cells”—stem cells collected from the circulating blood rather than from bone marrow—have been infused into patients instead of, or in addition to stem cells from bone marrow. Now it is possible to collect stem cells from umbilical cord blood and infuse them into a patient instead of bone marrow or peripheral blood stem cells. To date, more than 150 cord blood transplants have been performed worldwide.

Early Efforts

The first cord blood transplant was performed in 1988 in Paris, France. The patient was a 5-year boy with Fanconi anemia who is alive and disease free today. Since then, cord blood transplants have been successfully performed on patients with acute lymphocytic leukemia (ALL), acute myelocytic leukemia, neuroblastoma, juvenile chronic myelogenous leukemia (JCML), chronic myelogenous leukemia (CML), non-Hodgkin’s lymphoma, X-linked proliferative syndrome, severe aplastic anemia, Wiskott-Aldrich syndrome, Gunther’s disease, Beta-thalassemia, Hurler syndrome, myelodysplasia, and Hunter syndrome.

Although early cord blood transplants involved only sibling donors and recipients, 90 transplants were performed between August 1993 and November 1995 using cord blood from an unrelated donor. In most cases, the cord blood donors and transplant recipients were not HLA-matched, i.e., proteins on the surface of white blood cells (HLA-antigens) that play an important role in transplantation were not identical. Despite the mismatch, the transplants have been successful.

The Procedure

Collecting cord blood is a relatively simple procedure. Immediately after a baby is delivered, the umbilical cord is clamped. The baby is removed from the area and blood is then withdrawn from the umbilical cord with a needle and syringe. It is a painless, risk-free procedure for both mother and child. The cord blood is immediately transported to a facility where it is frozen at very low temperatures for future use. At the time of transplant, it is infused into the patient in much the same way that a blood transfusion is given.

“Cord blood transplants offer some potential advantages over bone marrow transplants,” says John Wagner, MD, director of the cord blood transplant program at the University of Minnesota Hospitals and Clinics in Minneapolis. “Collecting cord blood poses no risks or discomfort for the donor. Moreover, cord blood is rarely contaminated by viruses such as cytomegalovirus (CMV) or Epstein-Barr virus (EBV) that can cause serious problems for the transplant patient.”

In addition, patients transplanted with cord blood may have a lower risk of severe graft-versus-host disease (GVHD) than those transplanted with bone marrow. In graft-versus-host disease, certain cells in the donor’s bone marrow attack the patient’s organs and tissues, impairing their ability to function, and increasing the patient’s susceptibility to infection. Although most cases of graft-versus-host disease are mild or moderate, it is sometimes life-threatening.

Thus far, no patient transplanted with cord blood from a matched sibling donor has developed severe graft-versus-host disease. However, a few cases of severe GVHD have been reported in patients transplanted with cord blood from very mis-matched donors.

Limitations

Most cord blood transplants have been performed on patients weighing less than 40 kg (88 lbs). “The number of stem cells present in cord blood is significantly less than what’s routinely used in bone marrow or peripheral blood stem cell transplants,” explains Nancy Kernan, MD, Memorial Sloan-Kettering Cancer Center, New York. “We don’t yet know with certainty how many stem cells must be infused during transplant to ensure engraftment and production of new, healthy blood cells. Thus, until recently, researchers have been hesitant to perform cord blood transplants on adults.”

However, at least four adults weighing more than 70 kg (156 lbs) have now been successfully transplanted with cord blood stem cells. “The low concentration of stem cells in cord blood is a theoretical concern and may turn out to be less of a problem than originally believed,” says Kernan. “Alternatively, heavier patients who require higher doses of stem cells may be able to receive cord blood that has been manipulated in the laboratory to expand the number of stem cells present in the sample.”

Cord blood stem cells also engraft more slowly than stem cells derived from bone marrow or peripheral blood. Until engraftment occurs, patients are at risk of developing life-threatening infections. Thus far, however, the incidence of fatal infections in cord blood transplant patients does not appear to be higher than that observed in bone marrow or peripheral blood stem cell patients.

Cord Blood Banks

The ability to use cord blood instead of bone marrow in transplants has generated interest in developing cord blood banks. In collaboration with Memorial Sloan Kettering (New York), Mt. Sinai (New York), Duke University (North Carolina), and the University of Minnesota hospitals, the New York Blood Center has banked over 5,000 cord blood samples for use by persons who do not have a suitable bone marrow donor. Mothers about to give birth to a child sign a consent form allowing the hospital to dispose of the placenta, which makes it the property of the hospital. Prior to disposal, cord blood is collected and stored anonymously with extensive information about the family’s ethnic background, medical history, medical notes on labor and delivery, and results of tests for various bacterial and viral infections.

One concern voiced about anonymously banking cord blood is that a genetic disorder, not detectable at the time of birth, may subsequently develop in the donor. This information would not be available to the cord blood bank or transplant team. However, the probability of this happening is very low, says Wagner. “Most genetic diseases cannot be transmitted via a bone marrow or cord blood transplant. Moreover, there are several enzyme and DNA tests that can be performed on the cord blood sample that will rule out many genetic diseases.”

Several for-profit corporations now offer expectant mothers the opportunity to collect and store the infant’s cord blood after delivery. This ensures a source of stem cells for the child, should he require a stem cell transplant during his lifetime. Although the risk of developing a disease that must be treated with a stem cell transplant is relatively low, several families have opted for this “insurance” plan.

Future Directions

Cord blood stem cells may have uses beyond transplantation. “Stem cells have long been considered optimal vehicles for gene therapy,” says Wagner. “However, getting new genes into stem cells, which are capable of reproducing themselves throughout the life of the individual, has been extremely difficult. It’s recently been demonstrated that cord blood stem cells take up new genes more efficiently than bone marrow stem cells, making them an attractive vehicle for gene therapy.”

To date, three children with a life-threatening genetic disorder called adenosine deaminase deficiency have been treated with their own genetically corrected cord blood stem cells shortly after birth. Two years after treatment, the children still have the new gene present in their blood and bone marrow, which controls their disease. Other disorders that might be treated by genetically altered cord blood stem cells include metabolic diseases, HIV/AIDS, and bone marrow disorders such as Thalassemia and Fanconi Anemia, says Wagner.

“The ability to successfully transplant cord blood is an exciting development,” says Kernan, “particularly for patients who require stem cells from an unrelated donor. It’s feasible to build an ethnically diverse cord blood bank that can serve even those patients with rare HLA-types who are under-represented in current bone marrow donor registries. Moreover, the waiting time between donor identification and transplant is short—two to three weeks.”

The federal government is expected this spring to approve funding for a clinical trial that will carefully collect data on cord blood transplants. It’s also expected to establish cord blood collection centers and standards for collecting and storing cord blood samples. “A national cord blood bank will make stem cell transplantation a viable treatment for many more patients with life-threatening diseases,” Kernan says.

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