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Relying, in part, on the information that is emerging about the genetic basis of leukemia, investigators are pursuing a variety of strategies to control the disease -- approaches that can kill tumor cells directly, inhibit the body's production of substances that promote their growth, or that enhance the immune response against leukemic cells.
These investigational approaches are sometimes offered to eligible patients through the clinical trial process. Some of these research efforts are highlighted below. For up-to-date details about current clinical trials at Memorial Sloan-Kettering Cancer Center, please visit our clinical trial database.
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Refinements in Combination Chemotherapy
Drugs used in chemotherapy work in different ways to stop tumor cells from dividing, and to prompt them to undergo programmed cell death, or apoptosis. Physicians usually combine two or more agents in a course of treatment in an effort to kill as many tumor cells as possible. It is not yet known which regimen of combination chemotherapy is most effective for AML, so clinical trials are under way to compare the effectiveness of various combinations of chemotherapeutic agents.
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New Approaches to Transplantation
Investigators at Memorial Sloan-Kettering are studying ways to improve the outcome of bone marrow and stem cell transplants for leukemia patients who undergo these procedures. Sometimes, following a transplant, immune system cells transplanted from a donor perceive the recipient's body as foreign and attack his or her tissue. This serious condition is called graft-versus-host disease (GvHD). Researchers here are infusing patients whose disease has recurred after transplantation with gradually increasing amounts of T cells from the original donor. This approach takes advantage of the ability of donor immune cells to recognize and attack diseased cells in certain forms of leukemia. The low number of infused cells should attack the leukemia cells without causing significant GvHD. Transplants work best when they come from a genetically matched donor, but such donors are not always available. Researchers are evaluating the success of transplantation using high doses of stem cells from a related donor whose genetic type is at least half-matched with the patient. To minimize GvHD, researchers are testing the effectiveness of removing the T cells prior to transplantation.
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Monoclonal Antibodies
Monoclonal antibodies are genetically engineered proteins designed to target specific sites (antigens) on the surface of tumor cells. Researchers at Memorial Sloan-Kettering are testing a monoclonal antibody called HuM195 for its effectiveness against AML. HuM195 seeks out the antigen CD33, which is found on the surface of myeloid leukemia cells, and binds to it. Once bound with these cells, HuM195 causes them to rupture. In recent clinical trials, the antibody was found to eliminate minimal residual disease (leukemia cells detected after remission induction using extremely sensitive molecular tests) in up to half of patients. Researchers here are also investigating the effectiveness of HuM195 conjugated with (bound to) a radioactive substance, bismuth 213, which emits alpha particles that radiate the tumor cells. This type of radiation travels only a short distance from its source, limiting its overall toxicity.
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Growth Factors
Leukemia cells may be prompted to multiply when a protein called a growth factor binds with a specific growth factor receptor on the surface of diseased cells. Investigators at Memorial Sloan-Kettering are studying a specific receptor that may be active in AML called the vascular endothelial growth factor receptor (VEGFR), and are testing agents (called angiogenesis inhibitors) that will bind with the receptor and block its action.
Another promising avenue of research here is focusing on a specific mutation (FLT3) found on the leukemic cells of a third of AML patients. This mutation causes a particular enzyme involved in cell growth to be produced continuously, and this enzyme is responsible for the unchecked growth of blasts in AML. Investigators at Memorial Sloan-Kettering are conducting clinical trials of two experimental agents (PKC412 and CT53518) which block the action of the aberrant gene.
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Salicylates
Our researchers are studying the potential of a group of compounds called salicylates, which are found in common pain relievers, to induce apoptosis -- programmed cell death -- in myeloid forms of leukemia. These compounds may also potentially boost the effectiveness of chemotherapy or radiation therapy.
