| Disease Background | ||
| Description of Disease | ||
| Who is at Risk? | ||
| National Cancer Institute Dictionary | ||
| Our Research | ||
| Overview of Hutchinson Center Research | ||
Research Highlights
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| Treatment at the SCCA | ||||||||
| Blood Disorders | ||||||||
Hemophilia is a hereditary condition that results in blood that does not clot normally, resulting in serious risk of excessive bleeding (hemorrhaging), particularly internal hemorrhaging in joints, muscles and vital organs, especially the brain.
Two types of hemophilia exist. Classical, also known as hemophilia A or Factor VIII, has a lack of the Factor VIII protein in the blood that causes a problem with the clotting of blood. This is the most prevalent and serious form of hemophilia.
The second type, hemophilia B, is sometimes called Christmas Disease after Steven Christmas, a Canadian who in 1952 was the first person diagnosed with this distinct form of hemophilia. This form, also known as Factor IX deficiency hemophilia, occurs when the blood lacks the Factor IX protein which slows the normal clotting process.
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Hemophilia A and B are rare disorders that affect people of all races, colors and ethnic origins. In the United States approximately one in 10,000 people are diagnosed each year, mostly men. The most severe forms of hemophilia affect men almost exclusively, however, many women who are carriers of the disorder have symptoms of mild hemophilia. Researchers only recently have begun to fully recognize the importance of bleeding in women carrying the disorder.
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Overview of Hutchinson Center Research
Hutchinson Center researchers were the first to describe the molecular structure of Factor VIII, a protein implicated in hemophilia A. Knowing the structure of Factor VIII gives a first-hand glimpse at the subtle changes, often involving just a single, errant molecule, that cause this devastating bleeding disorder. The structure also may reveal clear targets for the rational design of better drugs to combat hemophilia.
Replacing the defective genes holds the greatest promise for a lifetime cure for hemophilia and other genetic disorders. Hutchinson Center researchers have long led the development of complex gene replacement technology. The development of this gene therapy depends on research in cell biology, gene transfer technology and the biology of disease. Multiple studies are under way to address these issues for various target cell populations, including blood, airway, skin, liver and muscle cells.
Researchers at the center pioneered the creation of a mechanism for delivering corrected genes into cells. Specially-engineered viruses (known as retroviruses) are used to transport the corrected genes to cells. These viruses were used in the first human gene-therapy trial in 1990 at the National Institutes of Health. This technology led to the development of the first commercially available retroviral gene-transfer kit, now used by researchers at academic medical centers and biotechnology firms worldwide.
Center researchers are continuing to improve techniques to correct genes. To date, the gene transfer rates are up to the 10 percent range using modified retroviruses. Research is also underway exploring additional methods to further improve rates of gene transfer and expression in blood cells to provide therapeutic tools for the treatment of a variety of inherited immune and blood disorders.
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Working to increase the effectiveness of transplants
The focus of Dr. Ann Woolfrey's research is to improve the effectiveness of bone-marrow and stem-cell transplants, particularly for patients with noncancerous (nonmalignant) disorders, such as aplastic anemia, sickle-cell anemia, hemophilia and thalassemia.
Through the conduct of clinical trials, Woolfrey works to bring advances made in the laboratory to clinical practice. In a recent study, Woolfrey and colleagues showed that 70 percent of the children diagnosed with acute lymphoblastic leukemia (ALL) who received transplants while in their first remission were cancer-free three years after treatment. Although this is the most common form of childhood cancer, doctors previously only considered transplants for patients with tissue-matched relatives. The researchers found that bone-marrow transplantation between tissue-matched, unrelated individuals is a viable option for young children, a finding that will enable many more young patients to benefit from this potentially lifesaving treatment. The findings indicate that transplantation should be considered for children with ALL who have no tissue-matched relatives as potential bone-marrow donors. This information may also be useful in determining when to treat children with other forms of cancer and genetic disorders.
Woolfrey's also seeks to improve the effectiveness of alternative donors, meaning unrelated and mismatched related donors, for children undergoing transplantation.
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Quest for effective bone marrow and stem cell transplants in children
Dr. Jean Sanders' research focus is on the development of more effective treatment options using bone-marrow and stem-cell transplantation for children diagnosed with leukemia, brain tumors, genetic and immune deficiency disorders.
For more than 30 years, in addition to her efforts to develop more effective transplant techniques, Sanders has made it her life's work to follow the lives of children who have survived bone-marrow or stem-cell transplantation to treat their cancers. Transplantation has raised the cure rates for many types of childhood cancer as high as 70 to 90 percent. Although quite effective, it often leaves long-term complications that must be monitored and treated.
Through patient care and clinical trials, Sanders works to understand the wide range of long-term effects of transplantation on growth hormones, bone-mineral density and pulmonary (lung) function.
As part of her research efforts and commitment to providing quality care, Sanders conducts a continuing care clinic where she treats 25 to 30 patients each month. Following these patients long after transplant has allowed her to not only treat post-transplant complications with the latest therapies available, but enabled her to gain a better understanding of how the complications develop.
Her research has shown that some pediatric patients who relapse after undergoing high-dose chemotherapy do very well with a second transplant while children who relapse after an initial transplant using a total-body irradiation-based regimen fare poorly after second transplant.
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Mini-transplants offer new hope to patients
Dr. Rainer Storb's clinical research team has successfully developed a radically different approach to bone-marrow transplantation that opens up the possibility of a cure for many more people. Because this new treatment, called mini-transplant or nonmyeloablative stem-cell transplant does not ablate, or wipe out bone marrow, patients experience minimal toxicity. The procedure is therefore safe enough to undergo in an outpatient clinic, and safe enough for many patients, formerly thought to be too old or too sick, to undergo the rigors of stem-cell transplantation.
Storb's team initially published results of an international study involving 46 patients with an average age of 56 years who underwent the new procedure. The study demonstrated that the new mini-transplant might offer hope to more patients with leukemia and nonmalignant blood disorders than ever before. Two-thirds of the study participants — patients who previously would have had little chance of a cure — had survived more than a year. Also, the radiation dose is six times lower than that used in a conventional transplant. So, most patients never need hospitalization, and few experience the toxic side effects such as painful mouth sores, severe nausea, hair loss or adverse heart and lung effects.
To date, more than 660 patients have received mini-transplants at the Hutchinson Center and a dozen other institutions. The longest survivor is more than six years post-transplant. The procedure eventually may be offered to a wide range of patients, offering an easier, lower-cost therapy for people with leukemia, myeloma, lymphoma, sickle-cell anemia and autoimmune diseases.
In addition to multiple studies aimed at further improving the results of the mini-transplant, Storb's team is examining the potential of immature blood stem cells to be changed into developing muscle cells or cells that line many organs and tissues in the body called, epithelial cells. Should such transdifferentiation, as it is called, prove feasible, it may become possible to regenerate muscle lost to such degenerative diseases as muscular dystrophy.
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