Blood and Marrow Transplant Program
The research programs of the Blood and Marrow Transplant (BMT) Program at Mayo Clinic Rochester are focused on improving the outcomes of blood and marrow transplantation for patients by making the procedure safer and reducing the risk of relapse of the patient's disease after transplant.
We have carried out and are planning future studies to also enhance the immune function of patients following autologous transplant in the hope that we can use these techniques to reduce the recurrence of their disease. These include studies using a novel cell of the immune system known as a dendritic cell to help stimulate the patient's immune system to fight their disease. Studies using immune stimulants such as low doses of interleukin-2 are also planned to reduce the risk of relapse of patients' diseases following autologous transplant.
Colleagues in the BMT Program have recently made the novel observation that patients who have a more rapid recovery of their blood lymphocyte count after autologous BMT have a significantly reduced risk of recurrence of their disease after transplant. Subsequent investigations have determined that lymphocytes known as natural killer cells are the most important cells mediating this effect. This phenomenon has been shown to be the most powerful predictor of outcome following both autologous transplant and has been shown to apply to each of the hematologic malignancies for which patients undergo transplant. The more rapid recovery of these cells after transplant appears to relate to the number of natural killer cells contained in the peripheral blood stem cell product collected for transplant. Recent studies have suggested that altering the way in which peripheral blood stem cells are mobilized can enhance the ability to collect these natural killer cells. On-going laboratory research in animal models will allow us to unravel the mechanisms by which these natural killer cells function to prevent tumor recurrence.
To increase the number of peripheral blood stem cells that we can collect from patients who will undergo autologous transplant, we have recently initiated studies here with a novel cytokine (a type of protein), AMD3100, which appears to function by increasing the number of stem cells released from the bone marrow during peripheral blood stem cell collection. This cytokine shows great promise for improving peripheral blood stem cell mobilization.
Because relapse of disease remains the main stumbling block to the success of autologous transplant and attempts to increase the amount of chemotherapy that can be given pretransplant to patients has reached its upper limits, studies in our program are looking at focused delivery of anti-tumor treatments to patients in an attempt to more effectively eradicate their underlying malignancy without increasing side effects. To this end, a monoclonal antibody linked to a radioactive substance known as a radionuclide is being studied in combination with chemotherapy to more effectively eradicate lymphoma cells as part of the autologous transplant. Seminal studies at Mayo Clinic Rochester led to the development of this novel monoclonal antibody-radionuclide combination known as Zevalin. We are collaborating with investigators at Northwestern University to study escalating doses of Zevalin combined with chemotherapy for autologous transplant for lymphoma.
Primary systemic amyloidosis
We are one of the leading centers in the United States which has pioneered the use of autologous peripheral blood stem cell transplant for the treatment of primary systemic amyloidosis. This disorder is a progressive fatal illness for which no other effective therapy currently exists. Our studies have shown that autologous transplant can prolong survival in patients with this devastating illness.
We are currently carrying out a comprehensive analysis of alterations in the clotting system following allogeneic and autologous BMT in an attempt to understand the clotting abnormalities that occur during transplant which can often lead to serious complications.
In the realm of allogeneic transplant, we have carried out studies assessing the role of family donors who are less than full immunologic matches with their family members in an attempt to extend lifesaving transplants to patients who would otherwise lack a suitable donor.
For the new form of allogeneic transplant known as reduced intensity conditioning transplant (also sometimes called "mini-transplants"), we are pioneering this approach in the rare disorder, myelofibrosis. Mayo Clinic is an internationally recognized center of excellence for the treatment of patients with myelofibrosis and use of this type of transplant has the potential to cure patients with this life-threatening disorder.
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