State of the Art in Umbilical Cord Transplantation

July 1, 1996

Every day thousands of babies are born in hospitals across America. These births offer opportunities to cure patients of leukemia and other life-threatening diseases. The opportunities lie in the routinely disposed placentas and umbilical cords.

Every day thousands of babies are born in hospitals acrossAmerica. These births offer opportunities to cure patients ofleukemia and other life-threatening diseases. The opportunitieslie in the routinely disposed placentas and umbilical cords. Researchershave found these to be rich sources of immature blood-formingcells (stem cells) that can be transplanted to patients needingbone marrow transplants as a potential cure for leukemia or otherdiseases. Instead of using bone marrow cells, transplant physiciansare now using umbilical cord blood (UCB) cells, also called placentalcord blood cells.

Bone marrow transplantation (BMT) is now a standard treatmentoption for patients with certain types of leukemia. In the transplantprocess, a patient receives high doses of radiation therapy and/orchemotherapy to prepare the body for the transplatn and hopefullyto kill whatever leukemia cells remain in the body. The normalbone marrow is killed as an innocent bystander. The marrow transplantis given to rescue or replace the normal bone marrow, using marrowcollected from a matched or partially-matched relative, from amatched or partially-matched unrelated adult donor, or sometimesfrom the patient (which has been collected before the radiationand/or chemotherapy). The transplanted cells then begin to growin the patient's body and to function as the body's blood factory,making blood cells that move into the circulatory system, performingfunctions that include carrying oxygen, fighting infection, andclotting the blood.

In an umbilical cord blood transplant, the patient receives thesame kind of preparative radiation therapy and/or chemotherapy,but instead of bone marrow, the patient receives umbilical cordblood cells. Similar to transplanted
bone marrow, the UCB cells begin to grow in the patient's bodyand make blood cells.

The first transplant of umbilical cord blood was performed in1989 in a patient with a nonmalignant blood disease. The umbilicalcord blood was collected when his baby sister was born and wasfrozen in a laboratory until the transplant. Since then, morethan 65 transplants using related cord blood have been performedin children and young adults with leukemia and other blood diseases,other cancers, and certain inherited metabolic diseases.

Unrelated Umbilical Cord Blood

Even more exciting is the use of unrelated umbilical cord bloodin transplantation. In 1992, an unrelated placental blood bankwas established by Dr. Pablo Rubinstein at the New York BloodCenter, with funding from the National Institutes of Health. Approximately5,300 units of umbilical cord blood have been collected at Mt.Sinai Hospital in New York City, tested for a variety of blood-bornediseases (such as HIV), tissue typed, frozen, and stored at theNew York Blood Center. In August 1993, the first unrelated umbilicalcord blood transplant in the world was performed at Duke University,using frozen unrelated umbilical cord blood from the PlacentalBlood Project's bank, in a 3-year-old patient with relapsed leukemia.Since then, more than 100 unrelated umbilical cord blood transplantshave been performed. The longest survivor to date is a boy whoreceived his unrelated umbilical cord blood transplant for infantleukemia in September 1993; he is a healthy, active, leukemia-free4-year-old.

Researchers are excited about the possibilities of umbilical cordblood transplantation for a number of reasons. First, the cordblood can be collected with no risk to the donor. The cost ofthis collection is also substantially less than the harvestingof bone marrow, which requires anesthesia and a short hospitalstay. Second, widespread collection of umbilical cord blood, especiallyin metropolitan areas, can significantly address the needs ofminority individuals who need transplants. The National MarrowDonor Program, the largest donor registry in the United States,is actively recruiting minority donors, but the vast majorityof registered volunteer donors are Caucasian. While it is notessential that ethnic backgrounds of donors and recipients match,there are certain tissue types that are more common in a givenethnic group, and minority and mixed-race individuals in needof unrelated marrow transplantation often cannot find donors throughthe National Marrow Donor Program.

Advantages of Umbilical Cord Blood

Umbilical cord blood transplantation also appears to offer advantagesto the transplant recipients. While relatively few unrelated cordblood transplants have been performed, physicians are findingthat UCB transplants can be successful even when the tissue typesof the cord blood and the donor are less well matched than withmarrow transplantation. Of the 35 unrelated umbilical cord bloodtransplants we have performed at Duke, only one has been a complete(6/6 antigen) match, and yet more than 70% of the transplantshave been successful. It also appears that a major, and potentiallyfatal complication of transplantation, graft-vs-host disease,may occur less frequently and with less severity in UCB transplantrecipients. UCB is also less likely to be contaminated with viruseslike cytomegalovirus, which may cause serious infections in transplantrecipients.

Although UCB appears very promising, several questions about itsuse remain the subject of current research. The most pressingis whether UCB can be used to transplant adults. Within the pastyear, a few UCB transplants have been successfully performed inolder children and adults, but further studies are necessary todetermine the extent to which this is possible.

What does the future hold? In the short-term, the National Heart,Lung and Blood Institute (part of the National Institutes of Health)is planning to find several additional cord blood collection banks.This will enable more people who need transplants, but lack arelated bone marrow donor, to find a source of transplantablecells and maybe a chance for a cure. Laboratory work is in progressto see whether cord blood cells can be multiplied before the cellsare transplanted; if successful, this could ultimately mean thata single unit of umbilical cord blood might be used to transplantmore than one person. As clinical trials of umbilical cord bloodtransplantation progress, researchers may find ways to make UCBtransplantation even more successful in curing leukemia and otherdiseases.

For more information on UCB transplants at Duke University MedicalCenter and cord blood storage, contact Connie Stephens at (919)684-8963. For more information on the New York Blood Center UCBBank, please call (212) 570-3230.

Statistics Source: John Wagner, md, International Cord Blood Registry,University of Minnesota, Box 366, Minneapolis, MN 55455.

Reprinted, with permission, from the Leukemia Society of Americafrom the spring 1996 issue of Newsline, the Leukemia Society'snational quarterly newsletter.