Helping Children with Non-Malignant Diseases

Helping Children with Non-Malignant Diseases

Stem Cell Transplants for Immune System & Blood Conditions

Well known for its effectiveness in curing cancer, bone marrow (or hematopoietic stem cell) transplants hold great potential for alleviating other types of diseases, too — especially those that involve the blood or the immune system. At Fred Hutchinson Cancer Research Center, a parent organization of Seattle Cancer Care Alliance (SCCA), our doctors can perform transplants for children with many hematologic or immunologic conditions, including juvenile rheumatoid arthritis, severe combined immunodeficiencies, aplastic anemia, and sickle cell disease.

“Most of these are rare diseases. Nonetheless, these disorders may prove life-threatening or have severe consequences on the quality of life,” explains Dr. Ann Woolfrey, the director of unrelated donor programs for pediatric transplants at the Hutchinson Center. This is why doctors continue to look for better treatment options and, ideally, cures. Part of Woolfrey’s work focuses on using and improving transplants for nonmalignant conditions.

Transplants for Diseases Other Than Cancer
Stem cells are immature blood cells that can divide to make more stem cells or, depending on the body’s needs, can develop into red blood cells, white blood cells or platelets. Red blood cells deliver oxygen around the body.

White blood cells defend against invaders and provide immunity. Platelets play a part in clotting to stop blood loss. A stem cell transplant, also called a hematopoietic cell transplant, uses stem cells taken from the bone marrow, peripheral (circulating) blood or cord blood of a donor. Sometimes the donor and recipient are one and the same — bone marrow or peripheral blood is removed from the patient and stored while the patient gets receives intensive chemotherapy and sometimes radiation. Then doctors return the stem cells from the marrow or blood to the patient to rebuild their blood-making system and immune system. This is called an autologous transplant. In other cases, doctors transplant cells from a different person. This type of transplant is called an allogeneic transplant.

Because a hematopoietic cell transplant replaces the recipient’s system for producing blood cells — including the white blood cells important for immunity — doctors believe this procedure may help cure a variety of nonmalignant diseases, just as it sometimes cures leukemia, lymphoma or other cancers. For some nonmalignant diseases, transplants have already been successful. Sickle cell disease is one example.

Normal red blood cells are round, soft discs, like doughnuts without holes. In sickle cell disease, red blood cells start out normal, but if they are stressed they become curved, hard and sticky. When cells “sickle” it is hard for them to move through the bloodstream. Though they are very small, the sickled cells can damage the blood vessels, keep blood from flowing well, and cause pain and other damage.

For most children, doctors can manage sickle cell disease by taking steps to prevent or treat infections, pain and complications of the disease. But for some, the disease is harder to control and causes serious complications.

When usual interventions do not work well enough, a hematopoietic cell transplant may be a solution. A transplant may succeed in providing the recipient with a new blood-making system that produces normal, non-sickled red blood cells.

In a similar way, transplantation may help children who have severe combined immunodeficiencies, other primary immunodeficiencies, aplastic anemia, Fanconi anemia or thalassemia. Some other genetic diseases may respond to a transplant, too, such as inborn metabolic disorders, like Hurler’s syndrome. So far, transplant outcomes have been poor for children with some of these conditions, says Woolfrey, “particularly for patients who have immundeficiencies and infections.”

“Our goal is to improve the transplant by reducing the intensity of the regimen that we give so there are fewer side effects from the treatment,” she says.

When the Body Attacks Itself
Another type of nonmalignant disease, called autoimmune diseases, may respond to a hematopoietic cell transplant. These are diseases in which the body’s immune system regards some of its own cells as foreign and attacks them. Examples include juvenile rheumatoid arthritis (JRA), systemic lupus erythematosis, and systemic sclerosis, also called scleroderma. “In Europe autologous transplants have been used to treat children with autoimmune diseases,” says Woolfrey.

Some centers in the United States, including the Hutchinson Center, also have been doing transplants for adults. The doctors at Fred Hutchinson Cancer Research Center pioneered the procedure in the United States, and transplants for children affected by autoimmune conditions are now being performed. Our first was performed a few years ago, for an adult who had JRA since childhood. As of publication time, our doctors had performed one other transplant for a child with an autoimmune disease, also JRA. Both patients have responded well to their transplants.

“The goal of the transplant is to reset the immune system, to remove the autoreactive immune system and allow the immune system to rebuild in the body without attacking the body,” Woolfrey explains.

Children with autoimmune diseases usually get adequate relief with standard treatments and do not need a transplant. “These diseases are not common, and most of them can be taken care of medically,” says Woolfrey.

But a small number of children are not helped by regular treatments, she explains, and may become crippled by their disease and have a poor quality of life. If all available medical therapies fail, then these children may be considered for a transplant.

Nonmyeloablative — or Mini Transplants
Before doctors transplant hematopoietic cells, recipients undergo an intensive regimen of chemotherapy (and sometimes radiation, too) to remove their bone marrow, the source of their problematic cells — for instance, cancerous cells in the case of leukemia and sickle-prone cells in the case of sickle cell disease. Ideally, the transplanted cells will engraft, or establish themselves in the recipient’s body and begin producing blood cells, taking over for the disabled marrow. The pretransplant regimen is called “conditioning.” Standard conditioning regimens can cause numerous side effects, some quite serious.

“Until recently, patients have not had other options, except for a standard transplant,” says Woolfrey. But since the late 1990s, doctors have used “mini transplants,” properly called non-myeloablative transplants, for some patients.

These involve a less intensive conditioning regimen. Doctors at SCCA and the Hutchinson Center sometimes use this type of transplant for nonmalignant diseases (as well as for cancer). “We pioneered use of the non-myeloablative transplant in these [nonmalignant] diseases,” says Woolfrey. “We have shown that this new procedure is very successful in reducing the risks of the transplant.”

Infections; heart, lung and liver problems; and need for blood transfusions — all possible complications of the standard conditioning regimen — have been reduced with nonmyeloablative regimens. Woolfrey is now developing a non-myeloablative transplant protocol to reduce the severity of graft-versus-host disease, in which transplanted cells regard the recipient’s cells as foreign and attack them.

Transplants for HIV
Non-myeloablative transplants have also been used for people who have human immunodeficiency virus (HIV). In these cases, doctors typically use a transplant for one of two reasons: (1) To provide a healthy immune system to HIV-positive people who take antiretroviral medicines but whose own immune system is not responding to the medicines, and (2) to treat HIV-positive people who develop leukemia or some other kind of cancer that can be treated with a transplant.

Very few facilities do transplants for people who are HIV positive because of concern that this procedure could allow the virus to grow uncontrollably. So far at the Hutchinson Center, our doctors have done one transplant for a person with HIV, and this patient, who is an adult, is responding well. Children with HIV may also be eligible for a transplant. As HIV becomes a chronic, manageable condition that people live with for many years, the option of a transplant may be increasingly important for some infected people, explains Woolfrey, which makes this an important area to explore and develop.