Children with bone marrow failure syndromes are often diagnosed early in life. Seattle Cancer Care Alliance and Seattle Children’s are the referral center for children and adults with bone marrow failure syndromes in the Pacific Northwest. Experts here offer state-of-the-art diagnosis and treatment for Fanconi anemia, Shwachman-Diamond Syndrome, Diamond-Blackfan anemia, dyskeratosis congenita, congenital thrombocytopenia, and others.
Often the best treatment for a child with a blood disorder or cancer is through a clinical trial. Dr. Akiko Shimamura, associate member at Fred Hutchinson Cancer Research Center, associate professor of Pediatrics at University of Washington, and an attending physician at Seattle Children’s is leading the way in many progressive bone marrow failure treatment trials.
While some patients may receive treatment for the effects of their disease, like platelet transfusions for bleeding symptoms or G-CSF for neutropenia, currently bone marrow transplantation is the only curative treatment. Treatment for Fanconi anemia ranges from androgen therapy, hematopoietic growth factors, or bone marrow transplantation, but gene replacement therapy is being studied at Fred Hutchinson Cancer Research Center as an alternative treatment. (*Read more in research section below.) And where Diamond-Blackfan anemia patients often receive corticosteroids or red cell transfusion support, here too, the only cure is transplantation.
The Fred Hutchinson Bone Marrow Transplant Program at SCCA was one of only two bone marrow transplant programs nationwide that consistently outperformed the expected one-year survival rate for unrelated donor transplants, according to an independent report that assessed 122 transplant centers over a five-year period.
BMT and Gene Therapy
Researchers at Seattle Children’s Hospital Research Institute, Fred Hutchinson Cancer Research Center, and the University of Washington are working to optimize bone marrow transplant and gene therapy for treatment of these disorders. Our hematologists work with transplant biologists to produce the best treatments possible for your patients with these rare, non-malignant diseases. Patients with many of these disorders require modified transplant regimens to avoid severe side effects. Hutchinson Center is a pioneer in the use of reduced intensity conditioning regimens for marrow failure patients.
Dr. Akiko Shimamura’s research interests are centered on understanding the molecular mechanisms contributing to hematopoiesis and tumorigenesis with the goal of extending basic research insights to the development of rationally designed therapeutic strategies. Her research group has focused on the inherited marrow failure syndromes, which have provided unique insights into novel molecular pathways contributing to hematopoietic failure and malignant transformation utilizing a range of experimental approaches including molecular and cellular biology techniques, biochemistry, viral vectors, high-throughput screening assays, hematopoiesis assays, and mouse genetic models.
She is investigating the function of the SBDS gene to understand how this gene contributes to marrow failure and leukemia with the goal of developing better treatments. She is also studying the role of ribosomes in inherited bone marrow failure and myelodysplastic syndrome. Further studies into the syndrome’s molecular pathways will help identify new ways to treat the disorder and prevent bone marrow failure and development of leukemia.
Gene Replacement Therapy
Dr. Hans-Peter Kiem, a medical oncologist and scientific investigator at Fred Hutchinson Cancer Research Center is researching another alternative known as gene replacement therapy for patients diagnosed with Fanconi anemia in complementation groups A and C. This type of therapy uses patients own blood cells that have been corrected for either the A or C complementation group defect.
More specifically, the FA patient’s bone marrow cells are collected and a correct copy of the FA gene that was mutated is stably transferred to the cells. These “corrected” bone marrow cells are then transplanted back into the patient. Because these cells come from the patient, the risk of an immune reaction, like GVHD or graft rejection, is lower. Also, the corrected cells have an advantage to survive over non-corrected cells once the transplant is complete. The hope is that this survival advantage will allow corrected cells to continue supporting the bone marrow and blood system of the patient and decrease the risk of aplastic anemia relapse.
North American Shwachman-Diamond Syndrome Registry
The new North American Shwachman-Diamond Syndrome Registry is based at Fred Hutchinson Cancer Research Center. Patients may contact the registry directly to receive enrollment packets and questionnaires. For more information or to join the registry, contact the Shwachman-Diamond Syndrome Registry Coordinator, Melissa Alvendia, at (206) 667-6965 or (866) 792-5876 or firstname.lastname@example.org.
Several Seattle Children’s physician researchers are conducting research to improve the diagnosis and treatment of Diamond-Blackfan anemia. Drs. Jan Abkowitz, Siobhan Keel, and Thalia Pappayanapoulou from University of Washington are conducting research on erythropoiesis, the process of producing red blood cells by the stem cells in the bone marrow.
Transplant Consultations and Patient Referrals
If your patients are candidates for transplantation, please contact the Transplant Program at Seattle Cancer Care Alliance for a consultation with one of our physicians at (800) 804-8824. Refer patients online at www.seattlecca.org/physician-referral.cfm
Meet Hans-Peter Kiem, MD
Dr. Hans-Peter Kiem received his medical degree from the University of Ulm in Germany in 1987. He is the José Carreras/E. Donnall Thomas Endowed Chair for Cancer Research and a member of Fred Hutchinson Cancer Research Center as well as a Professor of Medicine and Adjunct Professor of Pathology at the University of Washington School of Medicine. Dr. Kiem conducts preclinical and clinical studies of gene therapy. His clinical interests are hematopoietic stem cell transplantation, gene therapy, and graft-versus-host disease. Read more about Dr. Kiem.
Meet Akiko Shimamura, MD
Dr. Shimamura is a specialist in treating inherited bone marrow failure syndromes, such as aplastic anemia, Shwachman-Diamond syndrome, Fanconi anemia, dyskeratosis congenital, severe congenital neutropenia, and Diamond Blackfan anemia. Board Certified in Pediatric Hematology-Oncology, Dr. Shimamura graduated with her medical degree from University of Rochester School of Medicine, Rochester and Johns Hopkins University School of Medicine, Baltimore. She completed residency training at Johns Hopkins and Fellowship training at Boston Children’s Hospital/Dana Farber Cancer Institute, Boston, Massachusetts. Read more about Dr. Shimamura.
The SCCA Adult Bone Marrow Transplant News is a publication presenting the latest information on bone marrow transplant research at SCCA, providing up-to-date information for all health care professionals caring for transplant patients.
Read about important outcomes research at the Fred Hutch that may benefit your patients.
Each issue of Clinical Trials Monthly highlights several of the more than 200 clinical trials that are currently recruiting patients at SCCA.
Each quarterly Leading Edge newsletter will highlight a new topic to give you the latest news on leading-edge therapies that SCCA physicians are offering.