Marrow Transplants Offer Hope for “Incurable” Disorders

A generation ago, some kinds of leukemia and lymphoma were considered untreatable. Then, in 1968, a procedure called bone marrow transplantation was introduced, giving patients with these cancers and other serious diseases a new chance at life.

Today, the Medical College of Wisconsin is one of the leading centers worldwide for research into blood and marrow transplantation. The Medical College is home to two international blood and bone marrow transplant registries, the International Bone Marrow Transplant Registry and the Autologous Blood and Marrow Transplant Registry North America. These registries track the outcomes of transplants and search for ways to improve the technique.

In addition to research, the Froedtert & Medical College began its Blood Marrow Transplant (BMT) program in1980; since then, more than 1,000 bone marrow transplants have been performed here – not only for patients with leukemia and lymphoma but also for those with multiple myeloma and solid-tumor cancers. Blood and marrow transplants are also used for non-malignant blood disorders such as genetic anemias, immune deficiencies and sickle cell anemia, and in the treatment of breast cancer and multiple sclerosis.

The BMT program has a close association with the two blood and bone marrow registries at the Medical College, says Mary M. Horowitz, MD, MS, who is Scientific Director of both registries as well as a practicing transplant physician with the BMT program.

“We collect data on 10,000 new transplants a year from around the world,” Dr. Horowitz says, “and we currently follow 80,000 transplant survivors, some of whom had their transplants 30 years ago. By continually looking at this data bank, we stay very aware about what is going on in the field. We can bring that knowledge to our weekly patient planning meetings, and it gives us a foundation for making decisions and planning.”

Dr. Horowitz is also leading the Coordinating Center for a new Blood and Marrow Transplant Clinical Trials Network, which was launched in December 2001 with an $11 million grant from the National Heart, Lung and Blood Institute and the National Cancer Institute (both part of the National Institutes of Health). Leading cancer centers from around the country are participating in the effort to design clinical trials to develop better drug and treatment strategies for transplant patients.

Bone Marrow and Its Function
Bone marrow, a jelly-like substance, is found in the hollow bones of the hips, legs and arms. It contains hematopoietic (or blood-forming) stem cells, commonly referred to simply as stem cells. These cells are critical for life because they continually produce red blood cells that carry oxygen, white blood cells that help fight infections, and platelets that act as clotting agents to stop bleeding.

Cancers and other diseases affecting these blood-making cells have traditionally been difficult to cure because the chemotherapy or radiation (or both) that destroys the cancer also damages the normal blood-creating cells. With a transplant, doctors treat patients with high-dose therapy – effectively killing all the cells in the bone marrow – and then replace the damaged marrow with healthy marrow. Sometimes the healthy cells are collected directly from the bone marrow, in which case the procedure is termed a "bone marrow transplant." Sometimes the cells are collected from the bloodstream through a process called leukapheresis; the procedure is then called a blood stem cell transplant or simply a stem cell transplant.

Unlike an organ transplant, a bone marrow transplant procedure is not surgery but a series of injections. There are two types of blood and marrow transplants – autologous, in which the patient’s own blood stem cells are used; and allogeneic, which uses stem cells from a healthy donor, typically a relative, whose tissue type closely matches that of the patient. The decision to use the patient’s own blood stem cells or that of a donor for transplant depends on a variety of factors, including the type and stage of the disease

“The goal of the transplant is to cure patients of their primary disease with the fewest possible side effects,” says Carolyn Keever-Taylor, PhD, director of the Cell Processing Laboratories of the Blood and Marrow Transplant Program.

Genetic Testing Can Help Prevent Rejection
Potential complications of transplantation can include organ damage from chemotherapy, bleeding problems or rejection of the healthy cells. In some cases, the patient’s residual immune system, not destroyed by the chemotherapy, rejects the donor marrow. Another complication, called graft versus host disease, or GvHD, occurs when the donor marrow reacts against the body of the patient. GvHD only occurs in an allogeneic transplant, where the donor cells can recognize the recipient cells as "foreign." It is more common when the donor and recipient are not genetically matched for HLA, or Human Leukocyte Antigens.

Because the most desirable donor is a blood relative, family members such as brothers and sisters are among the first tested for compatibility. If no match is found, other family members may be tested. If that fails to yield a promising donor, a computerized search through the several worldwide donor registries is begun. (The largest of these is the National Marrow Donor Program, located in Minneapolis.) A search can take many months, depending on how common or rare the patient’s tissue type is.

At the Medical College, sophisticated tests including DNA sequencing are used to select the most closely matched unrelated donor. Many of these tests were pioneered by the Blood Center of Southeastern Wisconsin, working in partnership with the Medical College. The HLA Laboratory at the Blood Center is a pioneer in the development of molecular, or DNA-based, methods for determining the compatibility of transplant recipients and potential donors. Molecular typing methods have revealed that matches once considered ideal are, in fact, not perfect. In the future, molecular typing will be the standard method applied to bone marrow transplant patients. The Blood Center is a leader in the field of molecular typing.

Critical Need for More Donors
An essential partner in the Medical College’s Bone Marrow Transplant Program is the Blood Center of Southeastern Wisconsin. It supplies blood and blood products to support transplant patients and plays other key roles, including:

• collection and storage of blood cells essential for later use in transplants
• compatibility testing between potential donors and transplant recipients
• Sophisticated testing to determine how well a new transplant is growing in the patient
• Research and development of new laboratory technologies

Although many of these patients could be treated with a marrow or blood stem cell transplant, they need matching donors. And even though more than 4 million potential donors are on the national registry, the program estimates that only 30% will find a matching donor within their family, leaving the rest to search for an unrelated donor. At any given time, more than 3,000 patients are searching for a match. The need for non-Caucasian donors is especially severe.

Those interested in helping critically ill patients survive may contact the Blood Center of Southeastern Wisconsin for more information about taking a simple test for tissue typing and entry into the national registry. In the meantime, qualified individuals can also help transplant patients survive by donating whole blood or platelets. (Contact the Blood Center at 414-933-5000 for more information.) In the meantime, qualified individuals can also help transplant patients survive by donating whole blood or platelets, or by contributing to the research efforts of the IBMTR and ABMTR.

Barbara Abel
HealthLink Contributing Writer

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.