CXCR4 Antagonists In Acute Lymphoblastic Leukemias In NOD/SCID Mice
Funder
National Health and Medical Research Council
Funding Amount
$505,500.00
Summary
Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer and a major cause of death in children. Although ALL is usually responsive to chemotherapy, about 25% of children and 65% of adults with ALL develop a relapse of their disease. The majority of these patients will die of leukemia. New approaches to the treatment of ALL are necessary to obtain cures for these patients. We have identified stromal-derived factor (SDF)-1 as a major regulator of ALL cell growth and survival ....Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer and a major cause of death in children. Although ALL is usually responsive to chemotherapy, about 25% of children and 65% of adults with ALL develop a relapse of their disease. The majority of these patients will die of leukemia. New approaches to the treatment of ALL are necessary to obtain cures for these patients. We have identified stromal-derived factor (SDF)-1 as a major regulator of ALL cell growth and survival. It is currently the only known factor that significantly stimulates the growth-survival of cells from the majority of patients with ALL. Specific antagonists of the SDF-1 receptor, CXCR4, are available. Depriving ALL cells of SDF-1 by the use of these antagonists provides a radically new approach for the treatment of ALL. CXCR4 antagonists also increase the susceptibility of ALL cells to cytotoxic drugs. The mechanisms by which SDF-1 promotes ALL cell growth and survival are not known but appear to be largely due to synergistic interactions with other molecules that have little or no effect on their own. Knowledge of the underlying mechanisms of action of SDF-1 and the factors with which it synergises will facilitate for the further development of this approach. This project will examine the modulation of the expression of proteins that regulate ALL cell growth and survival by CXCR4 antagonists, providing insights into how CXCR4 antagonists work. This project will also extend our encouraging data obtained using tissue culture to an animal model of leukemia. The antagonists will be tested in isolation and in combination with currently used chemotherapy agents. It is expected that CXCR4 antagonists will inhibit the growth of ALL cells and increase their sensitivity to chemotherapy agents in the animal model as we have seen in laboratory culture. The addition of CXCR4 antagonists to current treatment protocols is expected to significantly improve the outcome for patients.Read moreRead less
Antagonists Of P38 MAPK As Therapeutics For Acute Lymphoblastic Leukemia.
Funder
National Health and Medical Research Council
Funding Amount
$521,961.00
Summary
New therapies are needed to treat patients with leukemia. Moving leukemic cells into the blood reduces their growth and increases the effects of chemotherapy. Currently we cannot move leukemic cells into the blood without moving normal blood forming cells, making them more sensitive to chemotherapy. We have identified a drug that only affects leukemic cell movement. This study will examine the potential of this drug to treat leukemia.
A Randomized Trial Of Idarubicin Dose Escalation In Consolidation Therapy For Adult Acute Myeloid Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$425,000.00
Summary
This project is a clinical trial to test the value of giving a higher than usual dose of one of the most important anti-cancer drugs, called idarubicin, in the initial treatment of adults with newly diagnosed acute myeloid leukemia (AML). This disease is the most serious form of leukemia in adults, and is usually treated with strong anti-cancer drugs, including idarubicin. Research in Australia and overseas has shown that increasing the doses of the other major drug (called cytarabine) used to t ....This project is a clinical trial to test the value of giving a higher than usual dose of one of the most important anti-cancer drugs, called idarubicin, in the initial treatment of adults with newly diagnosed acute myeloid leukemia (AML). This disease is the most serious form of leukemia in adults, and is usually treated with strong anti-cancer drugs, including idarubicin. Research in Australia and overseas has shown that increasing the doses of the other major drug (called cytarabine) used to treat AML in adults results in a doubling of the number of people cured of this disease, given that they have achieved a remission. This project will examine whether there is a similar benefit of increasing the idarubicin dose beyond that which has been conventionally used up to date. People who have AML diagnosed at one of the Australian hospitals participating in this study will receive initial treatment with an established drug combination. Those patients achieving a good response to the first treatment will then be randomly allocated to receive 2 further courses of treatment, one with a conventional dose of idarubicin, and the other with double the idarubicin dose. All patients will then be assesed for side effects of the treatment, and followed for at least 3 years for any signs of recurrence of their leukemia.Read moreRead less
A Clinical Trial Of Partially HLA-matched Unrelated Donor Microtransplantation For Prevention Of Relapse In Patients With Acute Myeloid Leukaemia Ineligible For Standard Haemopoietic Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$154,828.00
Summary
Acute myeloid leukaemia has a poor prognosis in patients unable to undergo bone marrow transplant, in particular in the elderly. No proven therapy improves their poor outcome. There is an urgent need to identify clinically applicable, non-toxic therapies for this group of patients. We will perform a clinical trial of "microtransplantation" using unrelated stem cell donors in combination with chemotherapy to try to reduce the relapse rate in these patients without the toxic effects of standard st ....Acute myeloid leukaemia has a poor prognosis in patients unable to undergo bone marrow transplant, in particular in the elderly. No proven therapy improves their poor outcome. There is an urgent need to identify clinically applicable, non-toxic therapies for this group of patients. We will perform a clinical trial of "microtransplantation" using unrelated stem cell donors in combination with chemotherapy to try to reduce the relapse rate in these patients without the toxic effects of standard stem cell transplantation.Read moreRead less
Cellular And Molecular Determinants That Regulate Osteoblasts At The Endosteal Niche During HSC Mobilisation
Funder
National Health and Medical Research Council
Funding Amount
$178,523.00
Summary
Treatments for leukaemia (e.g. chemotherapy) severely deplete immune and blood cells from patients. Transplantation of new blood forming cells (blood stem cells) into these patients is essential, but challenges are faced with isolating sufficient numbers in ways that preserve their ability to reconstitute the blood post transplant. My research aims to advance understanding of current methods used to isolate these cells and ultimately to improve the success of blood stem cell transplantation.