Bone Marrow Transplantation at Seattle Cancer Care Alliance

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Winter 2001

Seattle Cancer Care Alliance (SCCA) combines the best of the Pacific Northwest's world-class cancer research and patient care practices from the Fred Hutchinson Cancer Research Center (Hutchinson Center), UW Medicine (UWMC), and Children's Hospital and Regional Medical Center. Patients coming to the SCCA have access to some of the most advanced oncology therapies available anywhere in the world, and a variety of treatment options for malignant and non-malignant diseases, including bone marrow, stem cell, and cord blood transplantation. Since most of the therapies are research-based, patients may be enrolled in phase I, II, or III clinical trials.

Current Results

Bone marrow transplantation was developed by researchers at the Hutchinson Center-it is the most fundamental advance in cancer treatment of the last quarter century. Thousands of people have been treated with this life-saving therapy.

The Hutchinson Center has treated nearly 8,000 people with bone marrow transplants thus far. Each year, approximately 500 patients receive marrow transplants at the Hutchinson Center, UW Medicine, and Children's combined.

As a result of the Hutchinson Center's long-standing focus on transplantation, cure rates are among the highest reported, documented by statistics from the National Marrow Donor Program (NMDP). Recent reports show survival rates, five years after a matched sibling transplant, of 90 percent for severe aplastic anemia, 90 percent for chronic myelogenous leukemia, and 75 percent for acute myeloid leukemia in first remission.

A factor for improving transplant outcomes and increasing survival rates is the ongoing research to better understand and eliminate post-transplant complications. Studies at Hutchinson Center are currently focused on decreasing the incidence and severity of complications due to bone marrow transplants, such as acute graft-versus-host disease (GVHD).

Although bone marrow is the traditional source of hematopoietic stem cells used for transplantation, other cell sources now include peripheral blood and umbilical cord blood. Researchers at Hutchinson Center were among the first to show that stem cells harvested from peripheral blood were viable for autologous transplantation. Recent studies show that peripheral blood stem cells lead to faster engraftment, fewer post-transplant infections, less relapse of malignant disease, and significantly improved survival rates overall.

Another significant factor in improving transplant outcomes is the use of genetic typing for donor selection. Approximately one in three potential transplant candidates will have a suitably matched family member to serve as a donor. Through the NMDP there are more than three million people willing to donate marrow for patients who may not have a matched family member. Selecting the best match is a highly complex process. Researchers at Hutchinson Center have led the way in defining the most important genetic determinants of compatibility. While many centers still rely of serologic matching, physicians at Hutchinson Center now use genetic typing for donor selection. This method of donor selection, in addition to improvements made in supportive care, has improved the outcome of unrelated donor transplantation, making it very similar to matched sibling transplants for many categories of disease.

Additional research efforts are focused on the development of more targeted and non-abrasive therapies including:

• Radiolabeled monoclonal antibodies - Researchers at Hutchinson Center, UWAMC, and Children's pioneered the use of monoclonal antibodies to target high-dose radiotherapy to sites of malignant disease. When compared to standard total-body irradiation approaches, this technique allows for the delivery of higher doses ofradio therapy to sites of disease while sparing normal organs. Recent studies show survival rates as high as 75 percent five years after treatment.

• Antibody-targeted chemotherapy - Researchers at Hutchinson Center and Children's developed the concepts, performed the preclinical studies, and led the clinical trials that resulted in the very first antibody-targeted chemotherapy approved by the FDA. Mylotarg, a combination of an anti-CD33 antibody and the potent antitumor agent calicheamicin, was recently approved by the FDA as a safe and effective treatment for patients with recurrent AML. Hutchinson Center is now leading studies investigating the role of Mylotarg earlier in the treatment of AML.

• Non-ablative "mini" transplantation - Researchers at Hutchinson Center have shown that it is possible to perform less toxic marrow and stem cell transplant procedures while achieving stable and complete engraftment of allogeneic marrow from matched siblings or matched volunteer donors using a combination of chemotherapy and very low dose total-body irradiation. Such transplants can be carried out entirely in the outpatient setting and can be used to treat patients up to and even older than 70. Complete and enduring responses have been achieved in the majority of patients with progressive hematological malignancies. Major responses have been documented in renal cell carcinoma, colon cancer, and melanoma with this approach.