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Cord Blood: The Gift That Keeps on Living
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The gift of life surging through an umbilical cord reaches far beyond mother and baby. In a medical development even physicians call "phenomenal", blood from a newborn's umbilical cord and placenta has been found to be a rich source of life-giving stem cells - providing new hope for thousands of desperately ill people requiring bone marrow transplants unable to find suitable donors.

by Douglas Page 1999

For 30 years, bone marrow transplants have been the last resort of patients doomed by incurable blood diseases. Although still considered an experimental procedure by the U.S. Food and Drug Administration, bone marrow transplantation has been the only source of healthy stem cells needed in the replacement of diseased blood for patients with leukemia and lymphomas. Stem cells are the building blocks of the blood and immune systems. They form the white cells that fight infection, red cells that carry oxygen throughout the body and platelets that promote healing.

However, for bone marrow transplantation to first be considered, it is necessary to locate a donor whose blood fingerprint matches those of the recipient in six key protein indicators, called human leukocyte antigens (HLA). The chances of finding a match are best (one in four) among siblings or other family members. If a donor cannot be found among the patient's family, matches are then sought through what is often a long, frustrating and ultimately unsuccessful search of volunteer donor registries.

The odds (estimated at anywhere from one in 100 to one in two million depending of the patient's genetic makeup) aren't good. While computerized registries exist of four to five million donors worldwide, they succeed in making a match less than 30 percent of the time. The odds are even steeper for ethnic and racial minorities, who are under-represented on donor lists; less than 20 percent of the registrants have minority or mixed ancestry. Every year, according to the Journal of the American Medical Association, 10,000 to 15,000 people in the U.S. alone, for whom bone marrow transplants are their final hope, are unable to find suitable donors. Without a transplant they will die. A recent, tragic example of this was Michelle Carew, daughter of Baseball Hall of Famer Rod Carew; despite repeated public pleas, a match could not be found in time to save the child's life.

Even those fortunate few who win the registry lottery and receive transplants can't be certain the blood graft will take. Generally, within two years, about half of all transplants are rejected by a fatal side-effect called Graft vs. Host Disease (GVHD), the result of lymphocytes present in all grafts attacking the recipient.

STUNNING DISCOVERY

However, in 1974, things began to brighten a little in the bleak, punishing world of hematologic malignancy. Scientists make a stunning discovery. Stem cells, heretofore found only in bone marrow, existed in bountiful supply in the blood of a baby’s umbilical cord. And it was being tossed out at birth as just so much hazardous medical waste.

Researchers embraced the discovery, hoping it might affect two critical problems in bone marrow transplantation - the scarcity of suitable donors and the body's tendency to reject transplanted bone marrow as 'foreign'. Because cord blood comes from a newborn infant, it is unexposed to most diseases. Previous exposure to diseases jades adult bone marrow, making it more difficult to use in transplantation.

Experimental transplants using recycled cord blood from newborn siblings soon followed, with encouraging results, giving new hope to a few patients otherwise destined to perish.

The first came in 1988, in France, for a patient with Fanconi’s anemia. In 1991, cord blood was transplanted into a patient with chronic myelogenous leukemia. Both of these transplants were successful.

Since the patients given these novel transplants received the cord blood from newborn siblings, a spinoff technology began to evolve to freeze and store cord blood for exclusive use in the event the child, or a family member, later became ill. Several commercial enterprises currently exist for this purpose. The rejection problem was addressed by this breakthrough, but the lack of suitable donors remained.

Then, hematologist Pablo Rubinstein, MD, then a senior investigator and now director of the Placental Blood Program at the New York Blood Center, began to study how the baby's immune system - its white blood cells - tolerated the mother's blood cells. Why, he wondered, didn't the baby's blood attack, or reject, the 'invading' mother's blood? Something in nature must suppress the baby's immune function briefly until the mother's blood cells can be washed out of the baby's system. Unable to explain exactly how this worked, Rubinstein nevertheless theorized that there may be some advantage here if these cord cells were used in transplants for the thousands of patients needing transplants who were unrelated to the donor, who had no new baby in their families to provide that last hope.

In 1989 he approached the National Institutes of Health with a plan to collect and freeze cord blood, which, he believed, could significantly increase the supply of potential donors as well as the odds a patient will find a match. With the $4 million granted by NIH in 1992, Rubinstein thus established the first facility to bank, HLA-type, and freeze placental-cord blood collected from the delivery suites of area hospitals for use by anyone who can use it. Since then, cord blood banks have been established around the world.

Rubinstein supplied the tissue for the first two unrelated cord blood transplants in August and September, 1993, procedures performed by Joanne Kurtzberg, MD, director of the Pediatric Bone Marrow Transplant Program at Duke University Medical Center. "In 1994 we did 15, in 1995 we completed 100," Rubinstein recalls. "Currently, we have a little over 700 and are performing around 25 transplants per month worldwide."

Kurtzberg's results were reported in the July 18, 1997 issue of the New England Journal of Medicine. To date, Kurtzberg has performed about 160 unrelated pediatric cord blood transplants, three times as many as anyone else in the world. Half of these patients are surviving and appear to be cured of their diseases. All of them would have died otherwise. "All of the units were supplied by Dr. Rubinstein's bank," Kurtzberg says. "He has courageously pioneered this field against many obstacles. In my opinion, he has not received enough credit for his work."

That may change soon. In November, 1998, Rubinstein reported results of 600 new cases, including adult cord blood transplants, in the New England Journal of Medicine, validating the procedure. FDA approval is expected to follow, making it eligible for insurance claims.

Rubinstein's vision of an international cord blood banking system is already paying handsome interest. Diseased bone marrow is now being regenerated using blood donated from umbilical cords and placentas with outcomes as good or better than those using bone marrow. "It's quite encouraging," admits Rubinstein, who took a position of investigator at the New York Blood Center in 1972 after being educated at the Universidad de Chile. "People all over the world get very excited about this. In Japan, for example, the government has decided to establish a national cord blood system for transplantation. They already have nine banks. There are five in France paid by the government. In England there are three at the moment. Spain has five. Italy, I believe, has 17."

The success rate, just like for bone marrow transplants, depends on the patient's condition, disease, age, prior treatment and other complications. "But I think it can be safely said that in general this is as good as bone marrow for patients of approximately the same disease and general debility," Rubinstein says.

HIDDEN DIVIDEND

Cord blood transplants pays a hidden dividend. Rubinstein's paper reports a striking 40 percent decline in serious GVHD in all cord blood transplants. "The interest of cord blood transplantation in the unrelated area is that for reasons not entirely clear the cord blood reacts less immunologically against the recipient than bone marrow," Rubinstein says, "so you can do transplants in fact despite mismatches. With bone marrow, no one would dare make a transplant with more than one mismatch, but with cord blood we regularly do transplants with two mismatches. There have been a few, about five percent, that were done with three mismatches, and even those patients have survived very well with very little GVHD." No one is sure why this is, but preliminary evidence suggests it could be because the stem cells in the cord blood are immature, making them less immunologically fussy than those found in the marrow of older donors. Moreover, cord blood is rarely contaminated by viruses such as cytomegalovirus or Epstein-Barr that can cause serious problems for the recipient.

Cord blood matches are not only easier, the blood is available sooner. "Speed is of the essence for patients in remission from leukemia or with progressive genetic diseases," Kurtzberg says. "It takes two to six months from the point of initiating a search for a potential bone marrow match to transplant. It takes one to two weeks with cord blood. During the first years of the project, patients received cord blood if they did not have a suitable related or unrelated bone marrow donor. As the program has matured, we have moved to using cord blood instead of unrelated bone marrow for some patients."

Retrieval of bone marrow from the donor is invasive, painful and costly ($10,000 or more), involving extraction by needle and syringe under general anesthesia in a hospital setting. Cord blood, on the other hand, is already in the freezer, waiting.

"This is an extraordinary development," says University of Pennsylvania professor of medicine Stephen G. Gould, chief, Hematology/Oncology Division. "In the near term, it increases

the pool of unrelated but tissue type-matched stem cell donors for transplantation, so that nearly everyone should have a donor before long. In the future, it may also provide every individual with a banked source of their own stem cells, for a variety of anti-cancer treatments. This could be as revolutionary as blood transfusions were when they were first introduced."

Collection of cord blood is a quick, non-invasive and painless procedure with no risk to the mother or newborn. The collection can only take place at the time of delivery. The umbilical cord is clamped and cut in the same manner as it would be for any delivery. Using a sterile syringe or blood bag, as much of the 100 cc of cord blood as possible is drawn from the umbilical cord and packed in the special shipping material. It is then delivered to the laboratory within 24 hours of collection, where it is processed, separated and the stem cells cryogenically stored in liquid nitrogen.

No one is sure how long stem cells can be frozen and stored without degradation. Bone marrow has been successfully transplanted after having been stored for 15 years.

"The fact that this was once a discarded product and can now be life-saving is phenomenal," says Adrianna Vlachos, MD, assistant professor of pediatrics, Pediatric Hematology/Oncology, Mount Sinai Medical Center, New York. "Finding donors for patients with potentially life-threatening diseases, both malignant and genetic, has always been difficult. Finding them in a timely fashion is even more frustrating. Cord blood transplantation has attempted to solve both of these problems." A growing number of companies, hospitals, and physicians are working to educate the public about the value of umbilical cord stem cells and to provide a cord blood storage service for new parents for possible future use by their own children. Storing their baby’s umbilical cord blood stem cells, which costs from $300 to $1,500 up front, plus yearly storage charges of $75 to $150, affords their children the opportunity to take advantage of all the rapidly evolving, potentially life-saving medical technology. If ever necessary, umbilical cord blood stem cells can be a substitute for bone marrow transplants which treat a number of life-threatening diseases. Treatments involving radiation or chemotherapy often destroy the immune system.

In the event a transplant is ever needed, umbilical cord blood stem cells have a number of important advantages over bone marrow. Treatments using cord blood stem cells are less costly

than bone marrow transplants. Bone marrow transplants can cost $250,000. More importantly, however, is the fact that they are a perfect match for the child from whom they are collected, thus eliminating the difficult process of finding a matching donor and the risks of rejection.

The practice of private blood banking is not universally endorsed. "A better use of this resource is to establish a national bank," Kurtzberg says, "so people who desperately need it today can have that immediate access. That service - the commercial bank - is being offered as an insurance policy. But there are very few children who will ever need a transplant." Pablo Rubinstein's vision of a public bank, she says, makes units available to anyone who matches.

Since 1992, Rubinstein's band at the New York Blood Center has collected over 8,000 units of cord blood. With three new NIH-funded cord blood banks opening - at Duke, the University of Colorado in Denver, and UCLA - the overall pool is expected to be boosted by 15,000 units in the next two years. Officials are hoping as many as half the units collected will be from minority donors. The Duke bank is expected to increase the pool for African-American patients, while the bank at UCLA hopes to increase the number of units available for Asian and Hispanic patients.

Babies of every ethnic background are being born constantly - eight every minute just in the U.S.

"I look at cord blood transplant as a sort of poor-man's gene therapy," Kurtzberg says. "By replacing a child's marrow, we are essentially able to change the genetic makeup. There are certain genetic diseases, like SCIDS, Krebbe and Hurler's diseases, that have been effectively treated through cord blood transplant."

The nature of treatments for many diseases has changed radically over the past several years. Until recently, gene therapy was unheard of. As the causes of more diseases are discovered, more therapies will develop. It is possible the role of cord blood transplantation will assume Shakespearean dimensions, forming the core of new therapies. Already it is seen in the treatment of breast cancer and even HIV/AIDS.

Currently one in eight women in the United States develops breast cancer. Since mother and child are tolerant to one another in terms of matching HLA types, storing cord blood makes sense as a source of stem cells for the mother if it is ever needed.

Another exciting area developing in stem cell technology is the research into gene therapy to treat AIDS-infected individuals. Also, cord blood shows promise for the treatment of metastatic cancer and molecular medicine whereby defective genes are replaced with functional genes for diseases such as Sickle Cell Anemia, Hemophilia and many others.

In the end, the fertile deposits in Rubinstein's cord blood banks may be more precious than bearer bonds.

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Comments? Questions? Corrections? Assignments? douglaspage@earthlink.net
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